Innate Immune Activity Is Detected Prior to Seroconversion in Children

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Innate immune activity is detected prior to seroconversion in children

with HLA-conferred type 1 diabetes susceptibility

Henna Kallionpää,1,2,19,* Laura L. Elo,1,3,* Essi Laajala,1,4,5,19,*, Juha Mykkänen,1,6,18,19 Isis Ricaño

Ponce,7 Matti Vaarma,8 Teemu D. Laajala,1 Heikki Hyöty,9,10 Jorma Ilonen,11,12 Riitta Veijola,13

Tuula Simell,6,19 Cisca Wijmenga,7 Mikael Knip,14−16,19 Harri Lähdesmäki,1,4,19 Olli Simell,6,18,19

and Riitta Lahesmaa1,19

1Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI20521 Turku, Finland. 2Turku Doctoral Programme of Biomedical Sciences, FI20520 Turku, Finland. 3Biomathematics Research Group, Department of Mathematics, University of Turku, FI20014 Turku, Finland. 4Department of Information and Computer Science, Aalto University School of Science, FI00076 Aalto, Finland. 5The National Graduate School in Informational and Structural Biology, FI20520 Turku, Finland 6Department of Pediatrics, University of Turku, FI20014 Turku, Finland. 7University of Groningen, University Medical Centre, Department of Genetics, Groningen 9700 RB, The Netherlands 8Deparment of Signal Processing, Tampere University of Technology, FI33101 Tampere, Finland. 9Department of Virology, University of Tampere, FI33014 Tampere, Finland. 10Fimlab Laboratories, Pirkanmaa Hospital District, FI33520 Tampere, Finland. 11Immunogenetics Laboratory, University of Turku, FI20014 Turku, Finland. 12Department of Clinical Microbiology, University of Eastern Finland, FI70211 Kuopio, Finland. 13Department of Pediatrics, University of Oulu and Oulu University Hospital, FI90014 Oulu, Finland. 14Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, FI00014 Helsinki, Finland. 15Folkhälsan Research Center, FI00290 Helsinki, Finland. 16Department of Pediatrics, Tampere University Hospital, FI33521 Tampere, Finland. 17Department of Information and Computer Science, Aalto University School of Science, FI00076 Aalto, Finland. 18Department of Pediatrics, Turku University Hospital, FI20520 Turku, Finland. 19The Finnish Centre of Excellence in Molecular Systems Immunology and Physiology Research. *H.K., L.L.E., and E.L. contributed equally to this study.

CORRESPONDING AUTHOR: Riitta Lahesmaa, M.D., Ph.D., Professor Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, P.O. Box 123, FI20521 Turku, Finland. Tel. +358 2 333 8601 Fax +358 2 215 8808 Email: [email protected]

Short running title: Innate immune activity detected in prediabetes

Word count: 4134 Number of tables and figures: 7

Diabetes Publish Ahead of Print, published online February 18, 2014 Page 3 of 111 Diabetes

ABSTRACT

The insult leading to autoantibody development in children who will progress to develop type 1

diabetes has remained elusive. To investigate the genes and molecular pathways in the pathogenesis

of this disease, we performed genomewide transcriptomics analysis on a unique series of

prospective wholeblood RNA samples from atrisk children collected in the Finnish Type 1

Diabetes Prediction and Prevention (DIPP) study. We studied 28 autoantibodypositive children,

out of which 22 progressed to clinical disease. Collectively the samples covered the time span from

before the development of autoantibodies (seroconversion) through the diagnosis of diabetes.

Healthy controls matched for date and place of birth, gender and HLA-DQB1 susceptibility were

selected for each case. Additionally, we genotyped the study subjects with Immunochip to identify

potential genetic variants associated with the observed transcriptional signatures. Genes and

pathways related to innate immunity functions, such as the type 1 interferon response, were active

and interferon response factors (IRFs) were identified as central mediators of the interferonrelated

transcriptional changes. Importantly, this signature was detected already before the type 1 diabetes

associated autoantibodies were detected. Together, the data provide a unique resource for new

hypotheses explaining type 1 diabetes biology.

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By the time of clinical diagnosis of type 1 diabetes, an estimated 8090% of the insulinproducing pancreatic beta cells have been destroyed by autoimmune mechanisms with immune cells infiltrating the islets. Autoantibodies against beta cellspecific antigens, such as proinsulin and insulin, glutamic acid decarboxylase 65 (GAD65), islet antigen2 (IA2), and zinc transporter 8

(ZnT8), can usually be detected in serum before the clinical onset of the disease, but although the number of circulating autoantibodies is predictive for the development of type 1 diabetes (1), predicting the onset of clinical disease remains a challenge.

Susceptibility to type 1 diabetes is inherited, with the human leukocyte antigen (HLA) class II haplotypes encoding DR3DQ2 (DRB1*03-DQA1*0501-DQB1*0201) and DR4DQ8

(DRB1*0401-DQA1*0301-DQB1*0302) molecules conferring an estimated 50% of the total genetic risk. In addition, more than 40 nonHLA genes with more modest effect on disease risk, such as INS, CTLA4, PTPN22, and IL2R, have been discovered. When combined with a susceptible genetic background, largely unknown random environmental factors probably contribute to the breakdown of selftolerance. For instance, dietary factors, such as early exposure to foreign complex proteins (2) and vitamin D deficiency, have been associated with development of type 1 diabetes, and viral infections are believed to trigger autoimmunity (3, 4). Prevalence of type 1 diabetes is also associated with westernized lifestyle and level of hygiene (5).

To improve our understanding of the autoimmune processes driving the pathogenesis in the prediabetic phase in humans, we performed genomewide transcriptomics with two different array formats to determine gene expression changes that correlate with the development of diabetes associated autoantibodies and progression toward clinical diabetes. We analyzed a unique series of prospective wholeblood RNA samples collected in the Finnish Type 1 Diabetes Prediction and

Prevention (DIPP) study in which HLAsusceptible individuals are observed at frequent intervals from birth (6). For this study, we analysed blood samples taken from 28 atrisk children that

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collectively covered the time span from before the appearance of autoantibodies (seroconversion)

through the diagnosis of type 1 diabetes (Fig. 1). Healthy, persistently autoantibodynegative

children matched for date and place of birth, gender and the HLA-DQB1conferred genetic risk

were chosen as controls (Supplementary Table 1). Additionally, we genotyped the study individuals

using the Immunochip SNP array (7) to identify potential genetic variants associated with the

observed transcriptional signatures.

RESEARCH DESIGN AND METHODS

Subjects and Sample collection

All children studied were participants in the DIPP study (6), where venous blood was drawn into

PAXgene Blood RNA tubes (PreAnalytix) 1 – 4 times a year at the study clinic in Turku, Finland.

The samples were incubated for 2 hours at room temperature and then stored at −70 °C until

analyzed. Islet cell autoantibodies (ICA), insulin autoantibodies (IAA) and autoantibodies to GAD,

IA2 and ZnT8 were measured from all individuals. Of 28 subjects in this study, nine were sampled

starting before or at the time of the appearance of autoantibodies (seroconversion) (S15 and S710,

Table 1); six cases (S23, S710) were sampled before seroconversion, and four cases (S3, S6, S7,

and S10) progressed to type 1 diabetes. The remaining 18 children (D118, Table 1) were all

sampled starting after seroconversion and all progressed to diabetes (D118). A persistently

autoantibody negative control child was matched with each case, based on the date and place of

birth, gender and HLA-DQB1 genotype (Supplementary Table 1). In all, 356 blood samples (191

from seroconverters and TID children, and 165 from healthy controls) were processed for genome

wide transcriptional analysis.

Microarray hybridizations

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Total wholeblood RNA was extracted from the samples using PAXgene Blood RNA kit (Qiagen), and each sample was hybridized in duplicate both on Affymetrix and Illumina arrays according to manufacturer´s instructions. For Affymetrix, RNA was processed with Ovation RNA amplification system v2 including the Ovation whole blood reagent and hybridized to GeneChip Human Genome

U219 array plate (Affymetrix). For Illumina arrays, RNA was processed with RiboAmp OA 1 round RNA amplification kit (casecontrol pairs S1S6, Applied Biosystems/Arcturus) or Ovation

RNA amplification system v2 including the Ovation whole blood reagent (casecontrol pairs S7

S10 and all type 1 diabetes casecontrol pairs, NuGEN Technologies) and hybridized to Illumina

Sentrix human WG6 v2 expression bead chips (seroconverted casecontrol pairs) or Illumina

Human HT12 Expression BeadChips, version 3 (type 1 diabetes case control pairs).

Microarray data processing and statistical analysis

The gene expression microarray data were preprocessed using the RMA procedure for the

Affymetrix data and the quantile normalization procedure for the Illumina data using

R/Bioconductor (8). Differentially expressed genes were identified by comparing subjects with their matched healthy controls. Since the followup series are not fully synchronized in time between the different individuals, we first applied a similar approach as in (9) and (10) that avoids the need of a direct alignment. More specifically, for each individual, the expression intensity value of a particular probe/probeset x at each time point was given a zscore, defined as z=(xm)s1, where m is the mean and s is the standard deviation calculated using all the time points in the matched control time series. Such zscores penalize those probes/probesets that have high variability in the control series. To identify significant up or downregulation across the individuals, the rank product algorithm was applied to casewise maximum/minimum zscores (11). Genes with false discovery rate (FDR) below 0.05, estimated as the percentage of false positive predictions (pfp), were considered as differentially regulated. To focus on type 1 diabetes or seroconversionspecific changes the same procedure was applied to the data after swapping the case and control pairs. Only

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those probes were retained that did not pass the criterion FDR <0.05 in the swapped analysis. The

aim of the swapping procedure was to exclude from further analyses such nondiabetesrelated

changes that were similarly detected also in the controls. Finally, the findings from Affymetrix and

Illumina arrays were compared, and genes showing concordant changes were regarded as final,

validated findings (Supplementary Tables 2 and 3). Additionally, we required that the genes were

determined as present in more than 50% of all individuals (at least in one sample per individual)

using a twocomponent Gaussian Mixture model for the Affymetrix data and detection pvalues for

the Illumina data. Affymetrix and Illumina data were combined using the gene symbols provided by

IPA. To combine the data from the Illumina WG6 v2 and HT12 arrays, the probes between the

array types were matched based on their sequence similarity. 70% of the probes in Human WG6 v2

array had remained completely identical to the corresponding probes in the Human HT12 arrays. In

addition, we mapped 6% of the probes by requiring a minimum sequence overlap of 25/50

consequtive bases (one mismatch allowed). The probes also had to target the same gene according

to annotation. The remaining 24% of the probes were excluded from the analyses, for which the

WG6 v2 and HT12 data needed to be combined.

Pathway analysis

The functional annotation tool DAVID (Database for Annotation, Visualization and Integrated

Discovery) was used to identify enriched biological pathways (BBID, BioCarta, KEGG, Panther,

Reactome) among the regulated genes (12, 13). Pathways with FDR below 20% were reported

(modified Fisher's exact test).

Transcription binding motif analysis

Overrepresented transcription factor binding sites in the promoter regions (± 2 kilobases around the

transcription start site) of the regulated genes were identified using the transcription factor target

Diabetes Page 8 of 111 sets in the Molecular Signatures Database (MSigDB) (14). Binding sites with pvalue below 0.05 were reported (hypergeometric test).

Detecting differential expression in time-windows

In order to identify transcripts active in different phases of the autoimmune process, the rank product method was applied to find differentially expressed genes between the cases and their controls in five timewindows (see Fig. 1). The division was based on the maximal sample representation in each timewindow. Inside each timewindow, the fold change between the case and the matched control was calculated using linear inter/extrapolation. More specifically, the control sample series were matched to the time points of the case sample series. For the time points which were inside the range of real control time points this was performed by linear interpolation.

For the time points needed outside this range, the expression values were approximated by constant extrapolation (set equal to the closest real measurement). Genes with false discovery rate (FDR) below 0.05 were considered differentially regulated. Additionally, we required that the genes were determined as present, as described above. The findings validated with all array types (as described above) were regarded as changed.

In addition, we did a comparison between those seroconverted children (cases S3, S7 and S10) who had later progressed to type 1 diabetes, and those who have not been diagnosed with type 1 diabetes todate. An unpaired two group rank product analysis was performed for the casecontrol ratios to compare the affected and the unaffected cases. The analysis was performed for three timewindows: before seroconversion, at seroconversion, and 6−18 months after seroconversion.

Differentially expressed genes with functions related to the innate immunity responses

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The human genes with literatureannotated function in the innate immunity were downloaded from

www.innatedb.org (15). The enrichment of these genes among our differentially expressed genes

was calculated using Fisher’s exact test.

Transcription module analysis

A module based method modified from (16) was used to survey coordinately expressed sets of

genes (modules) functionally annotated with literature search. The gene symbols belonging to each

module were downloaded from www.biir.net/modules, and differentially expressed genes not

belonging to any of the modules presented in (16) were excluded from the analysis. The

significance of overlap of each of the 28 modules with each list of differentially expressed genes

was calculated using Fisher's exact test. Modules up or downregulated with the Benjamini

Hochberg corrected pvalue below 0.05 were visualized in the module maps with red or blue (up

and downregulation, respectively), the intensity of the color corresponding to the percentage of the

regulated probesets that belong to the module.

Immunochip data processing and statistical analysis

DNA from wholeblood was genotyped with the Immunochip array (7) in accordance with Illumina

protocols at the Department of Genetics, University Medical Centre Groningen (The Netherlands).

SNPs were mapped to NCBI build 36 (hg18). Quality control was applied using PLINK (17).

Samples with a call rate below 95%, as well as SNPs with a call rate below 98% were excluded.

Markers were excluded when they deviated from Hardy Weinberg equilibrium in the controls (P <

0.0001). SNPs with minor allele frequency below 10% were removed (N=80,259). Finally we

pruned our dataset based on LD between markers (r2>0.8). Our final dataset comprised 30,463

SNPs. Cis eQTL effects were calculated for each SNP residing within +250 kb around the gene

coordinates of each differentially regulated gene. A linear model was fit for genotype ~ gene

expression and a pvalue was calculated for the null hypothesis that genotype has no effect on gene

Diabetes Page 10 of 111 expression (slope = 0). Effects with BenjaminiHochberg corrected pvalue < 0.05 are reported

(Supplementary Table 7). The SNPs and their proxies (r2 > 0.8) that had an eQTL effect on our differentially expressed genes were searched for associations with autoimmune diseases in GWA studies, as listed in (18) and/or T1Dbase (19). The proxies for these SNPs were found based on

HapMap3 (release 2) and 1000 Genomes in the CEU population panel by using SNP annotation and proxy search (http://www.broadinstitute.org/mpg/snap/ldsearch.php).

Accession codes

The gene expression data discussed in this publication are accessible through GEO SuperSeries accession number GSE30211 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30211).

RESULTS

Gene expression signatures detected during seroconversion to autoantibody positivity

When the transcriptional profiles of S110 (Table 1) were compared to their matched healthy controls, 109 unique genes were differentially expressed (false discovery rate, FDR<0.05;

Supplementary Table 2), with 66% of genes being upregulated and 34% being downregulated.

Genes residing in the genomic type 1 diabetes susceptibility loci (T1Dbase (19)) included the upregulated oncostatin M (OSM) and the downregulated killer cell lectinlike receptor subfamily B member 1 (KLRB1) (Supplementary Fig. 1). The upregulated genes were enriched in the retinoic acid inducible gene 1 (RIGI)like receptor signaling pathway involved in recognizing viral dsRNA

(Supplementary Table 2).

Altogether, 12 unique transcription factor genes were differentially regulated in the seroconverted children (molecular type = transcription regulator, Supplementary Table 2). Analysis of known gene and protein interactions among these transcription factors and other genes in the dataset using

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the Ingenuity Pathway Analysis (IPA) network neighborhood tool showed that interconnected

interferon regulatory factors 5 and 7 (IRF5 and IRF7) had several coregulated network partners

(Fig. 2B and Supplementary Fig. 1). Additionally, IRF7 binding sites were enriched among the

promoters of the upregulated genes (P=0.000309, Fig. 2A and Supplementary Table 2). Both IRF5

and IRF7 are highly expressed in lymphoid tissues and drive the activation of a wide range of

antiviral genes. Target genes in the identified network (Fig. 2B) included for example the DEAD

box protein 58 (DDX58, better known as Retinoic acid inducible gene 1, RIG-I), which codes a

helicase involved in viral double stranded RNA recognition, as well as type 1 diabetes associated 2'

5'oligoadenylate synthetase 1 (OAS1), which codes for an enzyme involved in activating RNAse L,

resulting in viral RNA degradation.

Gene expression during the autoantibody-positive period preceding clinical type 1 diabetes

A comparison of the samples obtained from the 18 progressors (D118, Table 1) to their matched

controls revealed 472 differentially expressed genes (FDR<0.05; Supplementary Table 3). Notably,

gene expression was suppressed, as 73% of the differentially regulated genes in the progressors

were downregulated. The upregulated genes residing in the genomic type 1 diabetes susceptibility

loci (T1Dbase (19)) included the TRAFtype zinc finger domain containing 1 (TRAFD1) and the

signal transducer and activator of transcription 2 (STAT2). In contrast, the diabetesassociated

grancalcin (GCA) and the von HippelLindau binding protein 1 (VBP1) (2022) were

downregulated. (Supplementary Fig. 1). The top downregulated pathways were related to immune

system signaling, blood coagulation and complement (Supplementary Table 3).

Identification of transcriptional signatures characteristic for distinct phases of the diabetic

disease process

To identify transcripts that are active in different phases of the diabetic disease, we divided and

analyzed the data separately within five timewindows (Fig. 1). The number of samples available in

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each timewindow is summarized in Figure 3. In the timewindows before, at, or 6−18 months after seroconversion, 124, 33, and 551 genes were identified as differentially expressed (FDR<0.05), respectively; only 14 genes were identified that were common to all three time windows (Fig. 3A and Supplementary Table 4). During the intervals of 1−2 years before clinical diagnosis and at clinical diagnosis, 388 and 211 genes were differentially expressed between the progressors and controls, with 125 common genes (Fig. 3B and Supplementary Table 4). The two latest time windows overlapped with 47 genes that were differentially expressed before seroconversion (Fig.

3B). Different time windows showed enrichment of genes bearing different transcription factor binding sites, for example IRF and/or STAT binding sites were enriched in genes upregulated before seroconversion, and in the interval between seroconversion and diagnosis (Supplementary

Table 4). The overall suppression of the ribosomal proteins was presented as downregulated pathways named ribosome, metabolism of proteins, and 3`UTR mediated translational regulation

(Table 2 and Supplementary Table 4). In addition, by utilizing a wholeblood sample data analysis tool (16) that searches for presence of predefined groups of coordinately expressed transcripts

(functionally related, literatureannotated modules), we observed that the changes in transcriptional signatures were not stable but dynamic relative to different stages of type 1 diabetes pathogenesis

(Fig. 4 and Supplementary Table 5). For example the cytotoxic cell module (M2.1) was first downregulated at the earliest timewindow, but then induced at the time of clinical diagnosis. This module included for example killer cell lectin like receptors subfamily D and F member 1 (KLRD1,

KLRF1) that are expressed on natural killer (NK) cells, as well as granulysin (GNLY) that is expressed by both cytotoxic T cells and NK cells. However, a module consisting of interferon induced transcripts (M3.1), including for example the above mentioned antiviral OAS1 and DDX58, was constantly showing changes at almost every stage of the development of type 1 diabetes.

Transcriptional signatures distinct for progressors among the seroconverters

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Finally, we performed a separate timewindow analysis for the seroconverted children who later

progressed to clinical type 1 diabetes (cases S3, S6, S7 and S10, Table 1) compared to

seroconverted children who have remained nondiabetic for at least 73 months. For cases S3, S7,

and S10, data before, at, and 6−18 months after seroconversion were available.

Before seroconversion, nine genes were identified as differentially regulated (FDR<0.05;

Supplementary Table 6). At seroconversion and 6−18 months after seroconversion the difference

had increased to 13 and 54 genes, respectively. One of the genes showing constant and high

upregulation in the progressors was Ribonuclease, RNase A family, 2 (RNASE2, also known as

eosinophilderived neurotoxin, EDN, Fig. 5). It encodes a secreted protein with several

immunomodulatory functions. The ribonucleolytic activity of RNASE2 plays an important role in

eosinophilmediated antiviral activity against singlestranded RNA viruses. RNASE2 is an

endogenous TLR2 ligand (23) that could play a role in the induction of interferons. Most

interestingly, RNASE2 expression has been reported to be upregulated in the PBMCs of patients

with autoimmune diseases, such as rheumatoid arthritis (RA) (24) and systemic lupus

erythematosus (SLE) (25).

Identification of the genomic variants affecting the expression levels

In order to study the effect of possible single nucleotide polymorphisms (SNP) as the cause for the

detected expression differences, we utilized the Immunochip SNP array (Illumina) (7) for

genotyping. Using representative (LD pruned) SNP markers residing inside a window of +250 kb

around the gene coordinates, 118 differentially expressed genes had a cis eQTL (cis acting

expressed quantitative trait loci) effect with 154 SNPs per gene (FDR<0.05, Supplementary Table

7). Comparison to eQTLs recently identified in wholeblood from 5311 individuals (26) validated

27% of the detected cis effects (Supplementary Table 7). 14 of the identified eQTL genes (the

identified SNPs or their proxies r2>0.8), such as Histone cluster 1 H2bd (HIST1H2BD), have also

Diabetes Page 14 of 111 been associated with autoimmune diseases in GWAS, as listed in (18) and/or T1Dbase (19)

(Supplementary Table 7). Interestingly, eQTL effects were found with SNPs adjacent to IRF5,

OAS1, OAS2, DDX58, Transporter 2 ATPbinding cassette subfamily B (MDR/TAP) (TAP2),

Indoleamine 2,3dioxygenase 1 (IDO1) and Leukocyte immunoglobulinlike receptor subfamily A

(with TM domain) member 5 (LILRA5), which were identified as the core of the central interferon stimulatory network in the seroconverted individuals (Fig. 2B). Previously, SNPs overlapping the

TAP2 gene residing in the human MHC locus have been associated with type 1 diabetes in several studies (27, 28) and the IRF5 polymorphisms have been connected to SLE, RA, and inflammatory bowel disease (IBD) (2931).

DISCUSSION

This study provides a comprehensive analysis of transcriptional changes that occur over time in children at risk for or developing type 1 diabetes, and provide a unique resource for new hypotheses explaining the disease biology. Our results demonstrate that diabetesspecific changes are evident in the wholeblood transcriptome, affecting hundreds of genes. As the gene expression analysis was performed on wholeblood samples, we exploited the modulebased tool to suggest which cell types are important in different phases of the pathogenesis of type 1 diabetes (Fig. 4 and Supplementary

Table 5). For example the neutrophil module, including granule proteins such as lipocalin 2 (LCN2) and matrix metalloprotease 9 (MMP9), was first activated, after which the neutrophilassociated transcripts were suppressed before diagnosis, consistent with a recent report on reduced numbers of circulating neutrophils during the autoantibody positive phase as well as at the diagnosis of type 1 diabetes in humans (32). Also the erythrocyte related module was activated at early timewindows and before diagnosis. The platelet module, including coagulation factor XIII A1 polypeptide

(F13A1), was activated after seroconversion until clinical disease, which is in line with the reports on platelet hyperreactivity in type 1 diabetes (33). Interestingly, the cytotoxic cell module was suppressed before seroconversion but highly activated at the time of diagnosis, indicating the

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differential cytotoxic cell activity in the blood early vs. late in the disease process. However, as

detailed recording of the proportions of different cell populations at the time of the blood sample

draw is not available, these conclusions based on heterogeneous whole blood samples should be

further explored in future studies.

Taken together, our results indicate for the first time that type 1 interferon mediated innate immune

system is activated even prior to seroconversion and throughout the development of type 1 diabetes.

The induction is temporal, as expected for this systemic response, but some individuals show

several signature peaks during the followup period (Supplementary Fig. 1). Importantly, our

findings are consistent with the results of the accompanying study by Ferreira et al. (34), conducted

in an independent birth cohort of German children genetically susceptible for type 1 diabetes. They

also report that type 1 interferon signature is temporally increased in susceptible children prior to

the development of autoantibodies. These two independent longitudinal studies provide a unique

insight into the preclinical stage of type 1 diabetes.

In agreement with our results, Reynier et al. (35) recently reported that 12 interferon response genes

are upregulated in wholeblood of 30% of autoantibodypositive prediabetic children, but not in

healthy controls or recently diagnosed patients. Our data indicate that the interferon response can be

detected before the appearance of autoantibodies (Fig. 4), and that it consists of a much larger

number of genes than previously reported. In fact, comparison of the differentially regulated genes

to the genes listed to be involved in functions related to human innate immune responses in the

InnateDB (15) provides us with 17.4% overlap for the seroconverted children (19 genes,

P=0.0000003) and 9.5% overlap with the progressors (45 genes, P=value 0.0000013), respectively

(Supplementary Tables 2 and 3, InnateDB columns). Interferons α and β were not differentially

regulated in our data, indicating that the blood cells are showing an indirect response to cytokines

produced elsewhere. For instance, enteroviral infections have been detected in the beta cells of

Diabetes Page 16 of 111 newly diagnosed patients (36) and signs of infections have been observed a few months prior to seroconversion to autoantibody positivity (37) and during the 6month period preceding seroconversion (3, 4). Moreover, the accompanying study (34) demonstrates an association between upper respiratory tract infections and upregulation of interferon responsive genes. The correlation of gene expression profiles to markers of virus infections in susceptible children could make it possible to explore the mechanisms leading to the activation of the interferon system.

In addition, bacterial DNA, LPS, and flagellin are efficient triggers of TLR signalling and interferon response, providing an intriguing link between the gut immune system and autoimmunity. Both preclinical and established type 1 diabetes patients exhibit increased gut permeability (38, 39), leading to enhanced immune responses in the intestinal tissues (40). Also, a preliminary study has shown that gut microbiome diversity is reduced in children progressing towards type 1 diabetes compared to healthy controls (41). Moreover, the interferon response can be activated without infection by bacteria or viruses; for example, in SLE, IFNα production is driven by TLR7mediated signaling and is induced by autoantibodyproteinRNA complexes derived from apoptotic cells.

Also, endogenous TLR ligands such as RNASE2, that was identified to be upregulated in the seroconverters who later presented with type 1 diabetes, could play a role as it has been shown that spontaneous interferon production drives autoimmune diabetes in NOD mice (42).

In this study, the matching of the cases and controls was based on the HLA-DQB1 genotype. To take into account further susceptibility alleles and alterations affecting the transcriptional changes,

Immunochip SNP detection was performed for combinatorial analysis of the genome and transcriptome. This revealed that approximately 10% of the genes differentially expressed between the cases and controls were affected in cis by the genetic variation. The affected variants and genes have previously been linked to several autoimmune diseases, highlighting the shared genetic basis for these disorders. For example in the case of SLE, where strong type 1 interferon signature is also

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observed, the associated variations in IRF5 have been shown to control cytokine responses upon

TLR ligation (43). This pathway could be also genetically linked to type 1 diabetes, since only a

small part of the genetic factors conferring susceptibility to this disease have been identified. In

support of our findings, Heinig et al. (44) performed an expression quantitative trait loci (eQTL)

analysis across seven rat tissues combined with transcription factor binding site enrichment

analysis, resulting in the identification of Irf7 and 23 Irf7 target genes mapping to a single eQTL.

They subsequently identified a human IRF7driven network using genomewide expression and

SNP data collected from monocytes. Eventually, SNPs close to genes in the human and rat IRF7

network were found to be associated with T1D. Most importantly, of the 12 direct IRF7 target genes

(identified by the IPA tool) detected as differentially expressed in our study (Fig. 2B), 8 (66%) are

present in the human IRF7regulated network identified by Heinig et al. through a completely

different complementary approach further highlighting the role of this pathway in T1D

pathogenesis.

ACKNOWLEDGEMENTS

The work was financially supported by the Academy of Finland (the Centre of Excellence in

Molecular Systems Immunology and Physiology Research, 20122017, Decision No. 250114 to

R.L., O.S., M,K, and H.L. and grants 77773, 203725, 207490, 116639, 115939, 123864, 126063,

127575 (L.L.E.), 110432 (J.M.)), European Commission Seventh Framework grants (ECFP7

SYBILLA201106, ECFP7NANOMMUNE214281, ECFP7DIABIMMUNE202063, ECFP7

PEVNET261441, and ECFP7DIAPREPP202013), the Sigrid Jusélius Foundation, the Juvenile

Diabetes Research Foundation (JDRF), Turku University Hospital Research Fund, and Oskar

Öflund Foundation.

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H.K. analyzed the data, participated in the interpretation of the results, prepared the figures and was responsible for drafting and further writing of the manuscript. L.L.E analyzed the data, participated in the interpretation of the results, supervised E.L. and T.D.L., prepared the figures and contributed to the writing of the manuscript. E.L. analyzed the data, participated in the interpretation of the results, prepared the figures and contributed to the writing of the manuscript. J.M. participated in the initiation of the study, managed the RNA sample biobank, designed the study setup and participated in the data analysis, interpretation of the results and writing of the manuscript. M.V. and T.D.L. analyzed the data. I.R.P. and C.W. were responsible for the genotyping and SNP data quality control. H.H. was responsible for the virus analysis within the study. J.I. was responsible for the DNA isolation and HLA screening of the study children. M.K. and R.V. were responsible for the analyses of diabetesassociated autoantibodies. T.S. and O.S. provided the samples and the clinical information of the study children. H.L. supervised E.L. and M.V., and participated in the interpretation of the results. O.S. and R.L. initiated the study, designed the study setup, supervised the study, and participated in the interpretation of the results and writing the manuscript. All authors contributed to the final version of the manuscript. R.L. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Authors declare no conflict of interest relevant to this article.

This data has been published as a poster presentation in the 20th, 21st, and 23rd Biocity symposium, Turku, Finland, and as a poster and oral presentation in the Scandinavian Society for

Immunology meeting 2013 in Copenhagen, Denmark.

The authors are grateful for the DIPP families for their participation; S. Simell and the staff of the

DIPP study for their work with the families and obtaining the samples of the study; J. Hakalax, M.

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Laaksonen and E. Pakarinen for handling and managing the data of the study participants; V. Simell

for managing the DIPP biobank and samples; J. Tietäväinen for the help in the data analysis and M.

VähäMäkilä of the Department of Pediatrics of University of Turku for help in finalizing the

manuscript; P. Junni, R. Venho, E. Virtanen, and K. Waenerberg for their skillful technical

assistance and support in microarray hybridizations at the Finnish Microarray and Sequencing

Centre, Turku, Finland; M. Karlsson, T. Laakso, P. Nurmi, R. Suominen, and V. Öling for the help

with the DNA isolation; S. Sharma, E. Rothenberg and K.V.S. Rao for the fruitful discussion; and

A. Rao for critical review of the manuscript.

REFERENCES

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8. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J: Bioconductor: Open software development for computational biology and bioinformatics. Genome Biol 2004;5:R80 9. Elo LL, Mykkänen J, Nikula T, Järvenpää H, Simell S, Aittokallio T, Hyöty H, Ilonen J, Veijola R, Simell T, Knip M, Simell O, Lahesmaa R: Early suppression of immune response pathways characterizes children with prediabetes in genomewide gene expression profiling. J Autoimmun 201;35:7076

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LH, Karjalainen J, Withoff S, Uitterlinden AG, Hofman A, Rivadeneira F, 't Hoen PA, Reinmaa E, Fischer K, Nelis M, Milani L, Melzer D, Ferrucci L, Singleton AB, Hernandez DG, Nalls MA, Homuth G, Nauck M, Radke D, Volker U, Perola M, Salomaa V, Brody J, SuchyDicey A, Gharib SA, Enquobahrie DA, Lumley T, Montgomery GW, Makino S, Prokisch H, Herder C, Roden M, Grallert H, Meitinger T, Strauch K, Li Y, Jansen RC, Visscher PM, Knight JC, Psaty BM, Ripatti S, Teumer A, Frayling TM, Metspalu A, van Meurs JB, Franke L: Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat Genet 2013;45:12381243 27. Penfornis A, TuomilehtoWolf E, Faustman DL, Hitman GA, DiMe (Childhood Diabetes in Finland) Study Group: Analysis of TAP2 polymorphisms in finnish individuals with type I diabetes. Hum Immunol 2002;63:6170 28. CaillatZucman S, Bertin E, Timsit J, Boitard C, Assan R, Bach JF: TAP1 and TAP2 transporter genes and predisposition to insulin dependent diabetes mellitus. C R Acad Sci III 1992;315:535 539, 1992 29. Sigurdsson S, Nordmark G, Goring HH, Lindroos K, Wiman AC, Sturfelt G, Jonsen A, RantapaaDahlqvist S, Moller B, Kere J, Koskenmies S, Widen E, Eloranta ML, Julkunen H, Kristjansdottir H, Steinsson K, Alm G, Ronnblom L, Syvanen AC: Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am J Hum Genet 2005;76:528537 30. Sigurdsson S, Padyukov L, Kurreeman FA, Liljedahl U, Wiman AC, Alfredsson L, Toes R, Ronnelid J, Klareskog L, Huizinga TW, Alm G, Syvanen AC, Ronnblom L: Association of a haplotype in the promoter region of the interferon regulatory factor 5 gene with rheumatoid arthritis. Arthritis Rheum 2007;56:22022210 31. Dideberg V, Kristjansdottir G, Milani L, Libioulle C, Sigurdsson S, Louis E, Wiman AC, Vermeire S, Rutgeerts P, Belaiche J, Franchimont D, Van Gossum A, Bours V, Syvanen AC: An insertiondeletion polymorphism in the interferon regulatory factor 5 (IRF5) gene confers risk of inflammatory bowel diseases. Hum Mol Genet 2007;16:30083016 32. Valle A, Giamporcaro GM, Scavini M, Stabilini A, Grogan P, Bianconi E, Sebastiani G, Masini M, Maugeri N, Porretti L: Reduced circulating neutrophils precedes and accompanies type 1 diabetes. Diabetes 2013;62:20722077 33. Sobol AB, Watala C: The role of platelets in diabetesrelated vascular complications. Diabetes Res Clin Pract 2000;50:116 34. Ferreira RC, Guo H, Coulson RMR, Smyth DJ, Pekalski ML, Burren OS, Cutler AJ, Doecke JD, Flint S, McKinney EF, Lyons PA, Smith KGC, Achenbach P, Beyerlein A, Wicker LS, Todd JA, Bonifacio E, Wallace C, Ziegler A: Virallyinduced upregulation of type I interferon responsive genes is a precursor of type 1 diabetes autoimmunity in genetically atrisk children. Manuscript. 35. Reynier F, Pachot A, Paye M, Xu Q, TurrelDavin F, Petit F, Hot A, Auffray C, Bendelac N, Nicolino M, Mougin B, Thivolet C: Specific gene expression signature associated with development of autoimmune typeI diabetes using wholeblood microarray analysis. Genes Immun 2010;11:269278 36. Dotta F, Censini S, van Halteren AG, Marselli L, Masini M, Dionisi S, Mosca F, Boggi U, Muda AO, Prato SD, Elliott JF, Covacci A, Rappuoli R, Roep BO, Marchetti P: Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recentonset type 1 diabetic patients. Proc Natl Acad Sci U S A 2007;104:51155120 37. Hiltunen M, Hyöty H, Knip M, Ilonen J, Reijonen H, Vähäsalo P, Roivainen M, Lönnrot M, Leinikki P, Hovi T, Åkerblom HK: Islet cell antibody seroconversion in children is temporally associated with enterovirus infections. childhood diabetes in finland (DiMe) study group. J Infect Dis 1997;175:554560 38. Kuitunen M, Saukkonen T, Ilonen J, Åkerblom HK, Savilahti E: Intestinal permeability to mannitol and lactulose in children with type 1 diabetes with the HLADQB1*02 allele. Autoimmunity 2002;35:365368 20

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39. Bosi E, Molteni L, Radaelli MG, Folini L, Fermo I, Bazzigaluppi E, Piemonti L, Pastore MR, Paroni R: Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia 2006;49:28242827 40. WesterholmOrmio M, Vaarala O, Pihkala P, Ilonen J, Savilahti E: Immunologic activity in the small intestinal mucosa of pediatric patients with type 1 diabetes. Diabetes 2003;52:22872295 41. Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, Drew JC, Ilonen J, Knip M, Hyoty H, Veijola R, Simell T, Simell O, Neu J, Wasserfall CH, Schatz D, Atkinson MA, Triplett EW: Toward defining the autoimmune microbiome for type 1 diabetes. ISME J 2011;5:8291 42. Li Q, Xu B, Michie SA, Rubins KH, Schreriber RD, McDevitt HO: Interferonalpha initiates type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A 2008;105:1243912444 43. Hedl M, Abraham C: IRF5 risk polymorphisms contribute to interindividual variance in pattern recognition receptormediated cytokine secretion in human monocytederived cells. J Immunol 2012;188:53485356 44. Heinig M, Petretto E, Wallace C, Bottolo L, Rotival M, Lu H, Li Y, Sarwar R, Langley SR, Bauerfeind A, Hummel O, Lee YA, Paskas S, Rintisch C, Saar K, Cooper J, Buchan R, Gray EE, Cyster JG, Cardiogenics Consortium, Erdmann J, Hengstenberg C, Maouche S, Ouwehand WH, Rice CM, Samani NJ, Schunkert H, Goodall AH, Schulz H, Roider HG, Vingron M, Blankenberg S, Munzel T, Zeller T, Szymczak S, Ziegler A, Tiret L, Smyth DJ, Pravenec M, Aitman TJ, Cambien F, Clayton D, Todd JA, Hubner N, Cook SA: A transacting locus regulates an antiviral expression network and type 1 diabetes risk. Nature 2010;467:460464

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TABLES

Table 1 Summary of the two study groups, seroconverted children (S, n=10) and type 1

diabetes progressors (D, n=18) studied with genome-wide transcriptomics. See also

Supplementary Table 1 for more information on the cases and their matched controls.

Case Number of First sample from Last sample from Time of type 1 diabetes Age at type

longitudinal seroconversion seroconversion diagnosis 1 diabetes

RNA samples (months) (months) diagnosis

(years)

S1 8 0 23 na

S2 7 10 19 na

S3 7 12 12 20 months after last sample 7.7

S4 5 0 15 na

S5 4 0 14 na

S6 6 68 89 0 months after last sample 8.6

S7 9 37 12 22 months after last sample 9.3

S8 6 12 15 na

S9 10 40 3 na

S10 4 12 4 1 month after last sample 2.4

Case Number of First sample from First sample from Time of type 1 diabetes Age at type

longitudinal seroconversion diagnosis diagnosis 1 diabetes

RNA samples (months) (months) diagnosis

(years)

D1 7 17 33 at last sample 6.6

D2 6 51 13 0.6 months after last sample 6.6

D3 12 59 9 20.5 months prior to last sample 6.9

D4 7 49 20 at last sample 7.8

D5 8 39 31 at last sample 8.3

Diabetes Page 24 of 111

D6 6 3 30 3.2 months after last sample 8.8

D7 4 76 10 1.4 months after last sample 9.2

D8 12 86 46 3.2 months after last sample 12.1

D9 7 85 24 at last sample 10

D10 6 81 23 1.4 months after last sample 12.5

D11 8 na 32 at last sample 13

D12 6 3 15 at last sample 2.3

D13 5 3 16 at last sample 3

D14 5 11 14 at last sample 3.2

D15 8 3 27 at last sample 3.6

D16 9 2 27 0.3 months after last sample 3.8

D17 4 3 12 2.9 months after last sample 4.2

D18 5 30 24 0.4 months after last sample 4.9

Table 1. Summary of the seroconverted children (S) and type 1 diabetes progressors (D) studied with genome-wide transcriptomics. Seroconverted children (S1S5 and S7S10) were sampled starting before or at the time of the appearance of autoantibodies (seroconversion), except for S6, who was seropositive since the beginning of the followup. Cases S3, S6, S7, and S10 progressed to type 1 diabetes and the other six did not. The remaining 18 children (D118) were all sampled starting after seroconversion and all progressed to diabetes (D118). See also Supplementary Table 1 for more information on the cases and their matched controls.

Page 25 of 111 Diabetes

Table 2 Summary of the DAVID pathway analysis results in the five time-windows. Pathways

with FDR < 10% are presented. Red = pathways enriched among the upregulated genes, blue =

pathways enriched among the downregulated genes. See Supplementary Table 4 for further details.

Time-window Pathway term (DAVID) FDR P value Genes (%) Before hsa03010:Ribosome 8.84 0.011911 RPL26, RPS27L, RSL24D1 seroconversion At seroconversion No pathways

6-18 m after hsa04610:Complement and 0.49 0.000477 C3AR1, F5, SERPING1, seroconversion coagulation cascades C4BPA, C2, CFD hsa03010:Ribosome 0.03 0.000024 RPL17, MRPL13, RPL7, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPS27L, RPL39, RPS23 REACT_17015:Metabolism of 0.19 0.000210 RPL17, RPL26, VBP1, proteins RPS15A, RPL39, PIGK, PIGF, RPL7, RPS3A, RPL31, RPL9, PFDN5, RPS14, DPM1, RPS23, PIGA REACT_1762:3' UTRmediated 1.06 0.001189 RPL17, RPL7, RPL31, RPS3A, translational regulation RPL9, RPS14, RPL26, RPS15A, RPL39, RPS23 h_DNAfragmentPathway:Apoptotic 1.48 0.001414 HMGB1, HMGB2, CASP3, DNA fragmentation and tissue TOP2A homeostasis REACT_6167:Influenza Infection 4.21 0.004784 RPL17, RPL7, RPL31, RPS3A, RPL9, RPS14, RPL26, RPS15A, RPL39, RPS23, SNRPG hsa05012:Parkinson's disease 9.00 0.008457 NDUFA4, CASP3, COX7A2, NDUFS4, UBE2J1, COX7C, NDUFA1, UQCRQ, COX6C 1-2 y before T1D hsa05332:Graftversushost disease 0.73 0.000710 PRF1, HLAA, HLAC, diagnosis KIR2DL3, HLADQA1 hsa05330:Allograft rejection 6.36 0.006311 PRF1, HLAA, HLAC, HLA DQA1 REACT_6900:Signaling in Immune 5.48 0.007180 SELP, LY96, HLAA, HLAC, system TLR5, C2, KIR2DL3, PROS1, HLADQA1 hsa04940:Type I diabetes mellitus 9.63 0.009703 PRF1, HLAA, HLAC, HLA DQA1 hsa03010:Ribosome 0.00 0.000002 RPL36A, MRPL13, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPS27L, RPL39, RPS23 REACT_1762:3' UTRmediated 0.44 0.000519 RPL36A, RPL31, RPS3A, translational regulation RPL9, RPL26, RPS15A, RPL39, RPS23 REACT_6167:Influenza Infection 0.85 0.001011 RPL36A, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPL39, EIF2AK2, RPS23 REACT_17015:Metabolism of 1.73 0.002063 RPL36A, RPL31, RPS3A, proteins RPL9, RPL26, RPS15A, RPL39, PROS1, RPS23, PIGA REACT_6900:Signaling in Immune 3.36 0.004040 THBD, LY96, CD160, C1R, system TREM1, KIR2DL3, CFD, 24

Diabetes Page 26 of 111

KLRD1, PROS1, HLADOB, TLR8 At T1D diagnosis hsa05332:Graftversushost disease 0.16 0.000178 HLAA, GZMB, HLAC, KLRD1 hsa05330:Allograft rejection 4.25 0.004829 HLAA, GZMB, HLAC hsa04650:Natural killer cell 5.53 0.006321 HLAA, GZMB, HLAC, mediated cytotoxicity KLRD1 hsa04940:Type I diabetes mellitus 5.72 0.006533 HLAA, GZMB, HLAC hsa05320:Autoimmune thyroid 8.24 0.009527 HLAA, GZMB, HLAC disease hsa03010:Ribosome 0.03 0.000027 RPS26, RPL31, RPL9, RPL26, RPS15A, RSL24D1, RPL39, RPS23 hsa05310:Asthma 0.21 0.000206 FCER1A, HLADRB4, MS4A2, HLADOB, HLADQA1 hsa05330:Allograft rejection 0.48 0.000484 HLAA, HLADRB4, HLAC, HLADOB, HLADQA1 REACT_1762:3' UTRmediated 0.37 0.000493 RPS26, RPL31, RPL9, RPL26, translational regulation RPS15A, RPL39, RPS23 hsa05332:Graftversushost disease 0.66 0.000661 HLAA, HLADRB4, HLAC, HLADOB, HLADQA1 hsa04940:Type I diabetes mellitus 0.87 0.000878 HLAA, HLADRB4, HLAC, HLADOB, HLADQA1 hsa05320:Autoimmune thyroid 1.81 0.001830 HLAA, HLADRB4, HLAC, disease HLADOB, HLADQA1 REACT_6167:Influenza Infection 2.61 0.003467 RPS26, RPL31, RPL9, RPL26, RPS15A, RPL39, RPS23 hsa05416:Viral myocarditis 5.93 0.006104 HLAA, HLADRB4, HLAC, HLADOB, HLADQA1

Page 27 of 111 Diabetes

FIGURE LEGENDS

Fig. 1. Timing of blood sample collection showing time-windows used for temporal analysis of

the data. (A) Sample series of seroconverted children (S, marked with green color) and type 1

diabetes progressors (D, in red color) relative to the time from seroconversion (in years). Each black

diamond represents a blood sample that was subsequently analyzed by transcriptional profiling. For

the analysis of temporal changes in gene expression, samples representing three timewindows

relative to seroconversion were selected as follows: 1) before seroconversion (22 samples from 6

casecontrol pairs), 2) at the time of the seroconversion (8 samples from 8 pairs), and 3) 6−18

months after seroconversion (40 samples from 14 pairs). (B) Sample series of seroconverted

progressors (S, green color) and type 1 diabetes progressors (D, red color) relative to the time from

clinical diagnosis (in years). Samples representing two timewindows relative to diagnosis were

selected as follows: 4) 1−2 years before clinical diagnosis (48 samples from 19 pairs), and 5) at the

time of clinical diagnosis (18 samples from 18 pairs). (A−B) The timewindows were based on the

maximal representation of the samples. See Table 1 and Supplementary Table 1 for more details on

study subjects.

Fig. 2. Transcriptional regulation during the pathogenesis of type 1 diabetes. (A) Transcription

factor binding sites enriched among the promoters of the differentially up and downregulated genes

in the seroconverted individuals. Overrepresented sites in the ± 2 kilobase region around the

transcription start site of the regulated genes were identified using the transcription factor target sets

in the Molecular Signatures Database (MSigDB) (14). Binding sites with P < 0.05 and a known

transcription factor are presented (hypergeometric test). See Supplementary Table 2 for more

details. (B) Interferon regulatory factors 5 and 7 (IRF5 and IRF7), the most highly regulated

transcription factors in the seroconverted children, and their central role in the seroconversion

specific transcription. The network was generated with IPA network neighborhood tool, and it

Diabetes Page 28 of 111 shows all the IRF5 and 7connected genes (nodes) that were differentially regulated in the seroconverters (FDR < 0.05). The genes are organized according to their cellular localization, and red color indicates upregulation of the gene in the seroconverted cases compared to the matched controls. The genes regulating IRF5 or 7 are presented on the left, and the downstream target genes of IRF5 or 7 on the right. Solid edge indicates direct interaction, dashed edge indirect interaction.

Transcriptional induction/reduction is marked with green color, promoter binding with orange and mixed interactions with black. Black circles = genes having a cis eQTL effect with SNPs residing in a window of ±250 kilobases around the gene coordinates (Supplementary Table 7). White squares = genes belonging to the type 1 diabetes associated human IRF7mediated immune response network genetically identified by Heinig et al. (44).

Fig. 3. Transcriptional changes in distinct phases of the diabetic autoimmune process.

Numbers of regulated genes (FDR < 0.05, Supplementary Table 4) are listed for each timewindow in the analysis. N = number of casecontrol pairs in the analysis, n = number of samples in the analysis. (A) Timewindows before seroconversion, at seroconversion and 618 months after seroconversion. The overlapping 14 genes are listed on the right; Red = upregulated, blue = downregulated, black = mixed regulation between the timewindows. (B) Timewindows 12 years before clinical type 1 diabetes and at clinical type 1 diabetes diagnosis, and their overlap. The time window before seroconversion is presented with a dotted circle.

Fig. 4. Summary of the functional modules regulated in the distinct phases of development of type 1 diabetes. Upregulation or downregulation of the module (annotated groups of coordinately expressed transcripts from (16)) is marked with red or blue, respectively, and the color intensity indicates the percentage of the regulated genes belonging to that module. Module maps and genes belonging to each module in each timewindow are presented in Supplementary Table 5.

Page 29 of 111 Diabetes

Fig. 5. Ribonuclease RNase A family 2 (RNASE2) gene is upregulated in each seroconverted

cases who later progress to clinical type 1 diabetes. Longitudinal expression intensity profiles for

RNASE2 (probe set 11729772_at on Affymetrix U219 array) in seroconverted children (in orange)

and their matched autoantibodynegative controls (in black) are presented. Seroconverted children

3, 7 and 10 later progressed to clinical type 1 diabetes (20, 22 and 1 month after the last followup

sample, respectively), whereas seroconverted children 2, 8 and 9 have remained healthy todate.

The xaxis represents the age of the children (in days) and the yaxis the normalized logarithmic

signals on the arrays. The time of seroconversion for the progressors is marked with a dashed line.

Profiles for children with several measurements before seroconversion are presented (see Fig. 1,

Table 1, and Supplementary Table 6 for more details). *P < 0.05, **P < 0.01 between the case and

matched control (rank product test).

Diabetes Page 30 of 111

Fig. 1. Timing of blood sample collection showing timewindows used for temporal analysis of the data. (A) Sample series of seroconverted children (S, marked with green color) and type 1 diabetes progressors (D, in red color) relative to the time from seroconversion (in years). Each black diamond represents a blood sample that was subsequently analyzed by transcriptional profiling. For the analysis of temporal changes in gene expression, samples representing three timewindows relative to seroconversion were selected as follows: 1) before seroconversion (22 samples from 6 casecontrol pairs), 2) at the time of the seroconversion (8 samples from 8 pairs), and 3) 6−18 months after seroconversion (40 samples from 14 pairs). (B) Sample series of seroconverted progressors (S, green color) and type 1 diabetes progressors (D, red color) relative to the time from clinical diagnosis (in years). Samples representing two timewindows relative to diagnosis were selected as follows: 4) 1−2 years before clinical diagnosis (48 samples from 19 pairs), and 5) at the time of clinical diagnosis (18 samples from 18 pairs). (A−B) The timewindows were based on the maximal representation of the samples. See Table 1 and Supplementary Table 1 for more details on study subjects. 91x48mm (600 x 600 DPI)

Page 31 of 111 Diabetes

Fig. 2. Transcriptional regulation during the pathogenesis of type 1 diabetes. (A) Transcription factor binding sites enriched among the promoters of the differentially up- and downregulated genes in the seroconverted individuals. Overrepresented sites in the ± 2 kilobase region around the transcription start site of the regulated genes were identified using the transcription factor target sets in the Molecular Signatures Database (MSigDB) (14). Binding sites with P < 0.05 and a known transcription factor are presented (hypergeometric test). See Supplementary Table 2 for more details. (B) Interferon regulatory factors 5 and 7 (IRF5 and IRF7), the most highly regulated transcription factors in the seroconverted children, and their central role in the seroconversion-specific transcription. The network was generated with IPA network neighborhood tool, and it shows all the IRF5 and 7-connected genes (nodes) that were differentially regulated in the seroconverters (FDR < 0.05). The genes are organized according to their cellular localization, and red color indicates upregulation of the gene in the seroconverted cases compared to the matched controls. The genes regulating IRF5 or 7 are presented on the left, and the downstream target genes of IRF5 or 7 on the right. Solid edge indicates direct interaction, dashed edge indirect interaction. Diabetes Page 32 of 111

Transcriptional induction/reduction is marked with green color, promoter binding with orange and mixed interactions with black. Black circles = genes having a cis eQTL effect with SNPs residing in a window of ±250 kilobases around the gene coordinates (Supplementary Table 7). White squares = genes belonging to the type 1 diabetes -associated human IRF7-mediated immune response network genetically identified by Heinig et al. (44). 216x260mm (600 x 600 DPI)

Page 33 of 111 Diabetes

Fig. 3. Transcriptional changes in distinct phases of the diabetic autoimmune process. Numbers of regulated genes (FDR < 0.05, Supplementary Table 4) are listed for each time-window in the analysis. N = number of case-control pairs in the analysis, n = number of samples in the analysis. (A) Time-windows before seroconversion, at seroconversion and 6-18 months after seroconversion. The overlapping 14 genes are listed on the right; Red = upregulated, blue = downregulated, black = mixed regulation between the timewindows. (B) Time-windows 1-2 years before clinical type 1 diabetes and at clinical type 1 diabetes diagnosis, and their overlap. The time-window before seroconversion is presented with a dotted circle. 108x63mm (600 x 600 DPI)

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Page 35 of 111 Diabetes

Fig. 5. Ribonuclease RNase A family 2 (RNASE2) gene is upregulated in each seroconverted cases who later progress to clinical type 1 diabetes. Longitudinal expression intensity profiles for RNASE2 (probe set 11729772_at on Affymetrix U219 array) in seroconverted children (in orange) and their matched autoantibody-negative controls (in black) are presented. Seroconverted children 3, 7 and 10 later progressed to clinical type 1 diabetes (20, 22 and 1 month after the last follow-up sample, respectively), whereas seroconverted children 2, 8 and 9 have remained healthy to-date. The x-axis represents the age of the children (in days) and the y-axis the normalized logarithmic signals on the arrays. The time of seroconversion for the progressors is marked with a dashed line. Profiles for children with several measurements before seroconversion are presented (see Fig. 1, Table 1, and Supplementary Table 6 for more details). *P < 0.05, **P < 0.01 between the case and matched control (rank product test). 112x73mm (600 x 600 DPI)

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Supplementary Figure 1.

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Supplementary Figure 1. Time profiles of the differentially regulated genes described in the manuscript relative to the time of seroconversion or clinical diagnosis. Each open circle represents a blood sample of the case that was subsequently analyzed by transcriptional profiling. S denotes the seroconversion cases and D the type 1 diabetes progressors (Table 1). The color of the circles represents the signal log ratio (SLR) calculated against the matched control (red = upregulation, blue = downregulation).

Page 69 of 111 Diabetes

Samples of seroconverted cases Samples of matched control children Autoantibody status Time from Time from T1D HLA-DQB1 Age at sample seroconversion* diagnosis ICA > 4 IAA > 3.48 GADA > IA-2A > ZnT8A > HLA-DQB1 Age at sample Sample name Gender genotype (months) (months) (months) JDFU RU 5.36 RU 0.43 RU 0.61 RU Sample name Gender genotype (months) Case1_1 male *0302 110 0 no T1D diagnosis + Control1_1 male *0302 110 Case1_2 113 2 + Control1_2 115 Case1_3 116 6 + Control1_3 128 Case1_4 119 9 + Control1_4 134 Case1_5 125 15 + Control1_5 140 Case1_6 128 18 + + Case1_7 131 21 + + Case1_8 134 23 + Case2_1 male *02/0302 21 -10 no T1D diagnosis Control2_1 male *02/0302 19 Case2_2 25 -7 Control2_2 22 Case2_3 . 31 0 + Control2_3 27 Case2_4 35 3 Control2_4 39 Case2_5 41 10 Case2_6 45 14 + Case2_7 50 19 + Case3_1 female *02/0302 49 -12 -44 Control3_1 female *02/0302 55 Case3_2 55 -7 -38 Control3_2 62 Case3_3 61 0 -32 + + + Control3_3 67 Case3_4 66 5 -27 + + + Control3_4 73 Case3_5 67 5 -26 + + + Case3_6 70 9 -23 + + + Case3_7 73 12 -20 + + + Case4_1 male *02/0302 17 0 no T1D diagnosis + Control4_1 male *02/0302 19 Case4_2 20 3 + Control4_2 22 Case4_3 24 6 + + + + Control4_3 28 Case4_4 30 12 + + + + + Case4_5 33 15 + + + + + Case5_1 female *0302 12 0 no T1D diagnosis + Control5_1 female *0302 13 Case5_2 20 8 + + + Control5_2 16 Case5_3 24 12 + + + + + Control5_3 20 Case5_4 26 14 + + + + + Control5_4 37 Case6_1 female *02/0302 83 68 -21 + + + + + Control6_1 female *02/0302 78 Case6_2 86 71 -18 + + + + + Control6_2 84 Case6_3 91 76 -13 + + + + + Control6_3 90 Case6_4 94 79 -10 + + + + + Control6_4 96 Case6_5 101 86 -3 + + + + + Control6_5 102 Case6_6 104 89 0 + + + + + Control6_6 108 Case7_1 female *0302 43 -37 -71 Control7_1 female *0302 50 Case7_2 49 -30 -64 Control7_2 61 Case7_3 55 -24 -58 Control7_3 68 Case7_4 62 -18 -52 Control7_4 72 Case7_5 67 -12 -46 Control7_5 84 Case7_6 74 -5 -40 Control7_6 90 Case7_7 79 0 -34 + + Control7_7 96 Case7_8 86 7 -28 + + + + + Case7_9 92 12 -22 + + + + + Case8_1 male *02/0302 17 -12 no T1D diagnosis Control8_1 male *02/0302 12 Case8_2 19 -9 Control8_2 16 Case8_3 33 4 + + Control8_3 19 Case8_4 35 7 + Control8_4 22 Case8_5 40 11 + + Control8_5 31 Case8_6 43 15 + + + + Control8_6 37 Control8_7 43 Case9_1 male *02/0302 13 -40 no T1D diagnosis Control9_1 male *02/0302 16 Case9_2 15 -38 Control9_2 18 Diabetes Page 70 of 111

Case9_3 18 -35 Control9_3 22 Case9_4 22 -31 Control9_4 24 Case9_5 24 -29 Control9_5 30 Case9_6 30 -23 Control9_6 35 Case9_7 37 -16 Control9_7 42 Case9_8 44 -9 Control9_8 49 Case9_9 53 0 + + Control9_9 55 Case9_10 56 3 + + Case10_1 female *02/0302 13 -12 -17 Control10_1 female *02/0302 19 Case10_2 16 -9 -14 Control10_2 27 Case10_3 25 0 -5 + + + Control10_3 34 Case10_4 29 4 -1 + + Control10_4 40 Control10_5 46 Control10_6 52

*detection of first T1D-associated autoantibody (ICA, IAA, GADA, IA-2A or ZnT8A) Page 71 of 111 Diabetes

Samples of T1D progressors Samples of matched control children Autoantibody status Time from Time from T1D HLA-DQB1 Age at sample seroconversion* diagnosis ICA > 4 IAA > 3.48 GADA > IA-2A > ZnT8A > HLA-DQB1 Age at sample Sample name Gender genotype (months) (months) (months) JDFU RU 5.36 RU 0.43 RU 0.61 RU Sample name Gender genotype (months) T1DCase1_1 male *02 60 30 -20 + + + + + T1DControl1_1 male *02 55 T1DCase1_2 64 34 -16 + + + + + T1DControl1_2 61 T1DCase1_3 67 37 -13 + + + + + T1DControl1_3 67 T1DCase1_4 71 40 -10 + + + + + T1DControl1_4 73 T1DCase1_5 74 43 -7 + + + + + T1DControl1_5 79 T1DCase1_6 78 47 -3 + + + + + T1DCase1_7 80 50 0 + + + + + T1DCase2_1 male *02 67 51 -13 + + + + T1DControl2_1 male *02 67 T1DCase2_2 70 54 -10 + + + + T1DControl2_2 83 T1DCase2_3 72 57 -8 + + + + T1DControl2_3 117 T1DCase2_4 74 58 -6 + + + + T1DCase2_5 76 60 -4 + + + + T1DCase2_6 79 64 -1 + + + + T1DCase3_1 female *0302 75 59 -9 + T1DControl3A_1 female *0302 50 T1DCase3_2 77 61 -7 + T1DControl3A_2 64 T1DCase3_3 81 65 -3 + T1DControl3A_3 68 T1DCase3_4 83 67 -1 + T1DControl3A_4 72 T1DCase3_5 84 68 0 T1DControl3A_5 84 T1DCase3_6 86 70 2 + + T1DControl3A_6 90 T1DCase3_7 89 73 5 + + T1DControl3A_7 96 T1DCase3_8 92 76 8 + + T1DControl3B_1 female *0302 79 T1DCase3_9 95 80 12 + + T1DControl3B_2 86 T1DCase3_10 98 83 15 + + + T1DControl3B_3 91 T1DCase3_11 101 85 17 + + T1DControl3B_4 98 T1DCase3_12 104 88 21 + T1DCase4_1 female *02/0302 74 49 -20 + + T1DControl4_1 female *02/0302 67 T1DCase4_2 78 53 -16 + + T1DControl4_2 80 T1DCase4_3 81 56 -14 + + T1DControl4_3 85 T1DCase4_4 83 59 -11 + + T1DControl4_4 92 T1DCase4_5 86 61 -9 + + T1DControl4_5 97 T1DCase4_6 92 67 -3 + + T1DControl4_6 111 T1DCase4_7 94 70 0 + + T1DControl4_7 116 T1DCase5_1 male *02/0302 70 39 -31 + T1DControl5A_1 male *02/0302 66 T1DCase5_2 74 43 -27 + + T1DControl5A_2 72 T1DCase5_3 77 46 -24 + T1DControl5A_3 83 T1DCase5_4 81 49 -21 + T1DControl5A_4 89 T1DCase5_5 83 52 -18 + T1DControl5A_5 95 T1DCase5_6 88 56 -13 + T1DControl5A_6 101 T1DCase5_7 91 60 -10 + T1DControl5A_7 108 T1DCase5_8 101 69 0 + T1DControl5B_1 male *02/0302 73 T1DControl5B_2 80 T1DControl5B_3 86 T1DControl5B_4 91 T1DControl5B_5 98 T1DCase6_1 female *0302 77 3 -30 + + T1DControl6_1 female *0302 81 T1DCase6_2 79 5 -28 + + + + T1DControl6_2 94 T1DCase6_3 85 11 -22 + + + + T1DControl6_3 100 T1DCase6_4 94 20 -13 + + + T1DControl6_4 106 T1DCase6_5 97 23 -10 + + + T1DCase6_6 104 30 -3 + + + + + T1DCase7_1 female *0302 102 76 -10 + + + T1DControl7_1 female *0302 92 T1DCase7_2 105 78 -8 + + + + T1DControl7_2 97 T1DCase7_3 107 81 -5 + + + + + T1DControl7_3 105 T1DCase7_4 111 85 -1 + + + + + T1DControl7_4 109 T1DControl7_5 115 Diabetes Page 72 of 111

T1DControl7_6 122 T1DControl7_7 127 T1DCase8_1 male *0302 102 86 -46 + + + + + T1DControl8_1 male *0302 98 T1DCase8_2 104 89 -43 + + + + + T1DControl8_2 104 T1DCase8_3 107 91 -41 + + + + + T1DControl8_3 110 T1DCase8_4 110 95 -37 + + + + + T1DControl8_4 116 T1DCase8_5 113 98 -34 + + + + + T1DControl8_5 128 T1DCase8_6 117 102 -31 + + + + T1DControl8_6 134 T1DCase8_7 125 109 -23 + + + + + T1DControl8_7 140 T1DCase8_8 128 113 -20 + + + + + T1DControl8_8 147 T1DCase8_9 131 116 -16 + + + + T1DCase8_10 138 122 -10 + + + + T1DCase8_11 141 126 -6 + + + + T1DCase8_12 144 129 -3 + + + + + T1DCase9_1 female *02/0302 98 85 -24 + + + + T1DControl9_1 female *02/0302 92 T1DCase9_2 101 89 -21 + + + + T1DControl9_2 97 T1DCase9_3 104 91 -18 + + + + T1DControl9_3 104 T1DCase9_4 107 95 -15 + + + + T1DControl9_4 110 T1DCase9_5 113 101 -8 + + + + T1DControl9_5 122 T1DCase9_6 117 105 -4 + + + + T1DControl9_6 129 T1DCase9_7 122 109 0 + + + + T1DCase10_1 male *0302 129 81 -23 + + + T1DControl10_1 male *0302 116 T1DCase10_2 132 84 -20 + + + T1DControl10_2 122 T1DCase10_3 135 87 -17 + + + T1DControl10_3 128 T1DCase10_4 142 93 -10 + + + T1DControl10_4 134 T1DCase10_5 145 96 -7 + + + T1DControl10_5 140 T1DCase10_6 151 102 -1 + + + T1DControl10_6 146 T1DControl10_7 152 T1DControl10_8 158 T1DCase11_1 female *02/0302 126 unknown -32 + + + T1DControl11_1 female *02/0302 123 T1DCase11_2 129 unknown -28 + + + T1DControl11_2 130 T1DCase11_3 132 unknown -25 + + + T1DControl11_3 136 T1DCase11_4 135 unknown -22 + + + + T1DControl11_4 146 T1DCase11_5 139 unknown -19 + + + + T1DControl11_5 153 T1DCase11_6 144 unknown -13 + + + + T1DControl11_6 158 T1DCase11_7 155 unknown -3 + + + + + T1DControl11_7 165 T1DCase11_8 158 unknown 0 + + + + + T1DCase12_1 male *02 12 3 -15 + T1DControl12_1 male *02 14 T1DCase12_2 16 7 -12 + + T1DControl12_2 24 T1DCase12_3 19 10 -8 + + + T1DControl12_3 30 T1DCase12_4 22 13 -6 + + + T1DCase12_5 25 16 -3 + + + T1DCase12_6 28 19 0 + + + T1DCase13_1 male *02/0302 21 3 -16 + + + T1DControl13A_1 male *02/0302 16 T1DCase13_2 24 7 -13 + + + + T1DControl13A_2 25 T1DCase13_3 30 13 -7 + + + + T1DControl13A_3 31 T1DCase13_4 34 16 -3 + + + + T1DControl13A_4 43 T1DCase13_5 37 20 0 + + + + T1DControl13A_5 49 T1DControl13B_1 male *02/0302 21 T1DControl13B_2 25 T1DControl13B_3 40 T1DControl13B_4 46 T1DCase14_1 male *0302 26 11 -14 + + + + + T1DControl14_1 male *0302 37 T1DCase14_2 28 13 -11 + + + + T1DControl14_2 43 T1DCase14_3 33 17 -7 + + + + T1DControl14_3 49 T1DCase14_4 36 20 -4 + + + + T1DControl14_4 61 T1DCase14_5 39 24 0 + + + + T1DControl14_5 67 T1DCase15_1 female *0302 16 3 -27 + + + + T1DControl15_1 female *0302 13 T1DCase15_2 19 7 -24 + + + + T1DControl15_2 16 T1DCase15_3 22 9 -21 + + + + T1DControl15_3 20 T1DCase15_4 27 14 -17 + + + + T1DControl15_4 37 Page 73 of 111 Diabetes

T1DCase15_5 34 21 -10 + + + + T1DControl15_5 55 T1DCase15_6 37 24 -7 + + + + T1DCase15_7 39 26 -4 + + + + T1DCase15_8 43 31 0 + + + T1DCase16_1 male *0302 18 2 -27 + + + T1DControl16_1 male *0302 13 T1DCase16_2 22 6 -24 + + + + T1DControl16_2 15 T1DCase16_3 26 10 -20 + + + + T1DControl16_3 19 T1DCase16_4 28 12 -17 + + + + + T1DControl16_4 23 T1DCase16_5 32 16 -14 + + + + + T1DControl16_5 25 T1DCase16_6 35 19 -11 + + + + + T1DControl16_6 37 T1DCase16_7 38 22 -7 + + + + T1DControl16_7 43 T1DCase16_8 41 25 -4 + + + + + T1DControl16_8 48 T1DCase16_9 45 29 0 + + + + + T1DControl16_9 57 T1DCase17_1 male *02 40 3 -12 + + T1DControl17A_1 male *02 20 T1DCase17_2 43 6 -9 + + T1DControl17A_2 23 T1DCase17_3 46 9 -6 + + T1DControl17A_3 27 T1DCase17_4 49 12 -3 + + T1DControl17A_4 31 T1DControl17A_5 40 T1DControl17A_6 48 T1DControl17B_1 male *0302 41 T1DControl17B_2 46 T1DControl17B_3 52 T1DControl17B_4 58 T1DCase18_1 male *0302 36 30 -24 + + + T1DControl18_1 male *0302 31 T1DCase18_2 40 34 -20 + + T1DControl18_2 43 T1DCase18_3 43 37 -17 + + + T1DControl18_3 55 T1DCase18_4 56 50 -3 + + T1DCase18_5 59 53 0 + +

*detection of first T1D-associated autoantibody (ICA, IAA, GADA, IA-2A or ZnT8A) Diabetes Page 74 of 111

Differentially expressed genes in seroconverted cases (FDR < 0.05) showing concordant changes in Affymetrix and Illumina arrays, and information regarding the innate immunity function of the genes (InnateDB)

AFFYMETRIX Case vs. control Control vs. case ILLUMINA Case vs. control Control vs. case InnateDB (www.innatedb.org) Innate Immunity Genes in human. P value for overlap is 0.0000003. Affymetrix ID Gene Symbol (IPA) Gene name (IPA) Location (IPA) Type (IPA) Drug (IPA) Change probeset FDR max FDR min SLR max SLR min FDR max FDR min Illumina ID Gene Symbol (IPA) Change probeFDR max FDR min SLR max SLR min FDR max FDR min Gene Symbol (human)Pubmed ID Annotation 11726823_at ADORA3 adenosine A3 receptor Plasma Membrane G-protein coupled receptor adenosine, dyphylline,up aminophylline, clofarabine,0.02 theophylline, caffeine 1.37 0.76 ILMN_1730710 ADORA3 up 0.00 0.63 0.67 11750344_a_at ALOX15 arachidonate 15-lipoxygenase Cytoplasm enzyme up 0.02 1.31 0.54 ILMN_1676042 ALOX15 up 0.00 0.45 0.58 ILMN_1679410 ALOX15 up 0.00 0.43 0.48 11726243_a_at ANKDD1A ankyrin repeat and death domain containing 1A unknown other down 0.00 -0.98 1.06 ILMN_1813139 ANKDD1A down 0.00 -0.55 1.11 11733855_a_at APOL1 apolipoprotein L, 1 Extracellular Space transporter up 0.02 1.02 0.97 ILMN_1761793 APOL1 up 0.01 0.29 1.11 11735998_a_at APOL1 apolipoprotein L, 1 Extracellular Space transporter up 0.02 0.98 0.87 11741187_a_at APOL1 apolipoprotein L, 1 Extracellular Space transporter up 0.01 1.05 0.90 11753920_a_at APOL1 apolipoprotein L, 1 Extracellular Space transporter up 0.01 1.00 0.97 11763986_a_at APOL1 apolipoprotein L, 1 Extracellular Space transporter up 0.04 0.97 0.94 11745376_a_at APOL6 apolipoprotein L, 6 Extracellular Space transporter up 0.01 0.82 0.73 ILMN_1687201 APOL6 up 0.00 0.24 1.00 11724106_a_at BATF2 basic leucine zipper transcription factor, ATF-like 2 unknown other up 0.01 1.23 0.46 ILMN_1690241 BATF2 up 0.01 0.32 1.13 11750159_a_at BATF2 basic leucine zipper transcription factor, ATF-like 2 unknown other up 0.00 1.56 0.87 11716035_at BST2 bone marrow stromal cell antigen 2 Plasma Membrane other up 0.03 0.61 1.00 ILMN_1723480 BST2 up 0.00 0.93 0.32 BST2 19564354 BST2 directly binds to purified LILRA4 (ILT7) protein, initiates signalling via the ILT7-FcepsilonRIgamma complex, and strongly inhibits production of IFN and pro-inflammatory cytokines in plamsmacytoid dendritic cells 11716036_x_at BST2 bone marrow stromal cell antigen 2 Plasma Membrane other up 0.02 0.70 1.03 20702620 BST2 (CD317) is a broadly acting and conserved mediator of innate control of retroviral infection and pathogenesis that restricts the release of retroviruses and lentiviruses in rodents by limiting replication of HIV-1 and MLV. 11733022_at BTG1 B-cell translocation gene 1, anti-proliferative Nucleus transcription regulator down 0.02 -1.07 1.06 ILMN_1775743 BTG1 down 0.01 -0.44 1.10 21734563 BST2 is an innate intracellular HIV restriction factor that is upregulated by type I interferons. 11755220_a_at C17orf97 chromosome 17 open reading frame 97 unknown other down 0.00 -1.06 0.60 ILMN_1707137 C17orf97 down 0.00 -0.69 0.20 22072710 BST2 is a broad spectrum effector of the innate immune response to viral infection. BST2 is antagonized by the human immunodeficiency virus (HIV) Vpu protein to evade innate immune system detection. 11746124_x_at C21orf7 chromosome 21 open reading frame 7 unknown other down 0.03 -0.96 1.06 ILMN_1699071 C21orf7 down 0.01 -0.73 0.68 11747047_a_at C21orf7 chromosome 21 open reading frame 7 unknown other down 0.04 -1.10 1.04 11721099_at C3AR1 complement component 3a receptor 1 Plasma Membrane G-protein coupled receptor up 0.00 1.17 0.95 ILMN_1787529 C3AR1 up 0.00 0.64 0.95 11723949_a_at C4BPA complement component 4 binding protein, alpha Extracellular Space other up 0.00 1.68 0.81 ILMN_1810752 C4BPA up 0.00 0.47 0.38 C4BPA 21283780 C4BPA plays an inhibitory role in antimicrobial response by delaying the classical complement activation and attenuating the lectin pathway activation. The major inhibitory role of C4BPA is to facilitate the decay of C3 convertase. 11744719_x_at C4BPA complement component 4 binding protein, alpha Extracellular Space other up 0.00 1.69 0.29 11742124_a_at CACNG6 calcium channel, voltage-dependent, gamma subunit 6 Plasma Membrane ion channel up 0.04 1.07 1.01 ILMN_1779043 CACNG6 up 0.00 0.91 1.12 11719228_a_at CAMK1 calcium/calmodulin-dependent protein kinase I Cytoplasm kinase up 0.02 0.62 1.04 ILMN_1674514 CAMK1 up 0.01 0.58 1.13 11753343_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase up 0.03 1.36 0.62 ILMN_1722158 CASP5 up 0.00 0.98 0.31 11737492_a_at CCL23 chemokine (C-C motif) ligand 23 Extracellular Space cytokine up 0.00 2.43 0.84 ILMN_1686109 CCL23 up 0.00 1.07 0.18 11728039_s_at CCL8 chemokine (C-C motif) ligand 8 Extracellular Space cytokine up 0.00 1.41 0.23 ILMN_1772964 CCL8 up 0.00 0.42 0.43 11736620_x_at CCR6 chemokine (C-C motif) receptor 6 Plasma Membrane G-protein coupled receptor down 0.03 -0.78 1.06 ILMN_1690907 CCR6 down 0.01 -0.50 1.09 CCR6 21042003 CCR6 mobilizes TCR-alpha/beta+, CCR6+ innate and adaptive effector T cells in the airway in response to mycobacterial infection. CCR6 is not required for induction of the adaptive antimycobacterial response 11735864_a_at CD160 CD160 molecule Plasma Membrane transmembrane receptor down 0.00 -0.99 1.06 ILMN_1742001 CD160 down 0.00 -0.68 1.04 21376174 CCR6 is a chemokine receptor that only binds to a single chemokine ligand, CCL20. CCR6 is an important receptor that is involved in regulating mucosal immunity by mediating the recruitment of dendritic cells and APCs to the sites of epithelial inflammation. 11747113_a_at CD160 CD160 molecule Plasma Membrane transmembrane receptor down 0.05 -0.89 1.05 11763509_at CD9 CD9 molecule Plasma Membrane other up 0.04 0.80 1.08 ILMN_1679858 CD9 up 0.02 0.54 1.03 11751095_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other up 0.04 1.27 0.26 ILMN_1716815 CEACAM1 up 0.03 1.00 0.15 CEACAM1 18836450 CEACAM1 inhibits TLR2 induced pro-inflammatory immune responses by inducing PTPN6-(SHP-1)-mediated inhibition of the PI3K-NF-kappaB signal transduction pathway in pulmonary epithelial cells. 11760081_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other up 0.04 1.22 0.28 11750177_x_at CEACAM8 carcinoembryonic antigen-related cell adhesion molecule 8 Plasma Membrane other up 0.01 1.44 0.66 ILMN_1806056 CEACAM8 up 0.00 0.56 0.44 11758685_s_at CEACAM8 carcinoembryonic antigen-related cell adhesion molecule 8 Plasma Membrane other up 0.02 2.06 0.52 11734346_at CEBPE CCAAT/enhancer binding protein (C/EBP), epsilon Nucleus transcription regulator up 0.04 1.14 0.87 ILMN_1779095 CEBPE up 0.00 0.56 0.64 CEBPE 21326902 CEBPE is a member of the CCAAT enhancer binding protein family and is a transcriptional factor regulating genes in innate immunity and inflammation. The activities of CEBP are regulated via methylation of arginine and lysine side chains. 11721831_at CHURC1 churchill domain containing 1 Nucleus transcription regulator down 0.01 -0.31 0.31 ILMN_1732815 CHURC1 down 0.01 -0.28 0.11 11721832_s_at CHURC1 churchill domain containing 1 Nucleus transcription regulator down 0.01 -0.39 0.41 15208624 DDX58 (RIG-I) is a cytoplasmic RNA helicase that functions as an intracellular sensor of dsRNA leading to the induction of Interferon (IFN) production independently of TLR signalling. 11734956_a_at CNTNAP2 contactin associated protein-like 2 Plasma Membrane other down 0.00 -1.08 0.43 ILMN_1690223 CNTNAP2 down 0.02 -0.54 0.36 18948594 DDX58 (RIG-I) first and second caspase recruitment domains (CARDs) have distinct roles in TRIM25-mediated RIG-I ubiquitination, which leads to initiation of an antiviral signalling cascade. 11720069_s_at COMMD8 COMM domain containing 8 unknown other down 0.02 -1.16 1.06 ILMN_1765644 COMMD8 down 0.03 -0.54 1.03 19074283 DDX58 serves as a critical link between TLR3 and type-II-IFN signalling pathways in innate antiviral immune responses. 11719480_a_at CSTA cystatin A (stefin A) Cytoplasm other down 0.03 -1.13 1.05 ILMN_1669888 CSTA down 0.02 -0.48 1.10 19683681 DDX58 plays an essential role in Toll-like receptor (TLR)-stimulated phagocytosis, demonstrating that DDX58 plays a role not only in antiviral responses but in antibacterial responses as well. 11733149_a_at DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 Cytoplasm enzyme up 0.01 1.00 0.64 ILMN_1797001 DDX58 up 0.00 0.83 0.21 DDX58 18523264 DDX58 plays a key role in the expression of TNF-alpha in macrophages in response to LPS stimulation, mainly for the late phase LPS-induced expression of TNF-alpha. 11755819_a_at DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 Cytoplasm enzyme up 0.01 0.86 0.11 19915568 DDX58 is a sensor able to activate the inflammasome in response to certain RNA viruses by binding to the adaptor PYCARD to trigger the caspase-1 (CASP1)-dependent inflammasome activation and IL-1-beta production. 11732546_at DEFA4 defensin, alpha 4, corticostatin Extracellular Space other up 0.00 2.05 0.84 ILMN_1753347 DEFA4 up 0.00 0.85 1.09 DEFA4 20403326 DDX58 binds specifically to K63-polyubiquitin chains through its tandem caspase recruitment domains (CARDs) that act as a ubiquitin sensor in a manner that depends on RNA and ATP, demonstrate that un-anchored K63-polyubiquitin chains are signalling molecules in antiviral innate immunity. 11721897_a_at DHX58 DEXH (Asp-Glu-X-His) box polypeptide 58 Cytoplasm enzyme up 0.02 0.63 0.60 ILMN_1678422 DHX58 up 0.00 0.52 0.42 DHX58 20406818 DDX58 (RIG-I) phosphorylation on serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction. 11749497_a_at DHX58 DEXH (Asp-Glu-X-His) box polypeptide 58 Cytoplasm enzyme up 0.01 0.63 0.52 20511549 DDX58 innate immune response to viral infection of human cells is modified by a functional polymorphism in the RIG-I caspase recruitment domain (CARD). 11731775_a_at EMR1 egf-like module containing, mucin-like, hormone receptor-like 1 Plasma Membrane G-protein coupled receptor up 0.02 0.94 0.83 ILMN_1780601 EMR1 up 0.00 0.68 0.85 19936053 DDX58 (RIG-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response. (Demonstrated in murine model) 11748205_a_at EMR1 egf-like module containing, mucin-like, hormone receptor-like 1 Plasma Membrane G-protein coupled receptor up 0.01 1.05 0.84 21690088 DDX58 and NOD2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. DDX58 negatively regulates ligand-induced NFkB signalling mediated by NOD2, and conversely, NOD2 negatively regulates type I interferon induction by DDX58. 11736143_s_at ENPP4 ectonucleotide pyrophosphatase/phosphodiesterase 4 (putative) unknown enzyme down 0.02 -1.07 1.03 ILMN_1693675 ENPP4 down 0.02 -0.65 1.08 21695051 DDX58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus to suppress viral replication. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of DDX58. 11759423_at EPPK1 epiplakin 1 Cytoplasm other up 0.05 0.74 0.88 ILMN_1764263 EPPK1 up 0.00 0.52 0.24 22072774 DDX58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling. (Demonstrated in mice) 11722573_a_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase down 0.00 -1.62 1.04 ILMN_1743145 ERAP2 down 0.00 -0.99 0.84 22912779 Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse) 11745601_a_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase down 0.05 -0.63 1.04 19024344 DEFA4 along with DEFA1 and DEFA3 are cationic alpha-defensin peptides that have multiple functions in the immune system. 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase down 0.00 -0.87 1.05 17190814 DHX58 (LGP2) helicase is related to DDX58 (RIG-I) and IFIH1 (MDA5) but lacks caspase activation and recruitment domains (CARDs), and functions as a negative regulator of innate host defence. 11762512_a_at ERICH1 glutamate-rich 1 unknown other down 0.00 -1.14 1.03 ILMN_1731001 ERICH1 up 0.03 0.43 1.00 16210631 DHX58 lacks the caspase recruitment domain (CARD) homology and functions as a negative regulator by interfering with the recognition of viral RNA by DDX58 (RIG-I) and IFIH1 (MDA5). ILMN_1904238 ERICH1 down 0.00 -0.59 1.02 16116171 DHX58 functions as a negative regulator of antiviral innate immunity by interfering with the recognition of viral RNA by DDX58 (RIG-I) and IFIH1 (MDA5). 11720023_a_at FAM118A family with sequence similarity 118, member A unknown other down 0.01 -0.52 0.18 ILMN_1809147 FAM118A down 0.01 -0.27 0.08 11746669_a_at FAM118A family with sequence similarity 118, member A unknown other down 0.02 -0.50 0.15 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other down 0.00 -0.91 0.83 ILMN_1687213 FAM167A down 0.00 -0.37 1.09 11742889_at FBXO6 F-box protein 6 Cytoplasm enzyme up 0.02 1.04 0.59 ILMN_1701455 FBXO6 up 0.00 0.75 0.20 11733439_a_at GBP5 guanylate binding protein 5 Plasma Membrane enzyme up 0.04 1.02 0.19 ILMN_1779798 GBP5 up 0.01 1.22 0.24 11763755_a_at GNLY granulysin Cytoplasm other down 0.00 -1.41 1.03 ILMN_1790692 GNLY down 0.03 -0.97 1.10 ILMN_1708779 GNLY down 0.03 -0.92 1.08 11737911_a_at GPR84 G protein-coupled receptor 84 Plasma Membrane G-protein coupled receptor up 0.03 1.19 0.17 ILMN_1785345 GPR84 up 0.01 0.35 0.13 11758625_s_at GSTA4 glutathione S-transferase alpha 4 Cytoplasm enzyme down 0.03 -0.87 1.03 ILMN_1771964 GSTA4 down 0.04 -0.19 1.02 11718578_a_at GSTM3 glutathione S-transferase mu 3 (brain) Cytoplasm enzyme up 0.04 0.82 0.88 ILMN_1736184 GSTM3 up 0.00 0.30 0.79 11727401_x_at HOPX HOP homeobox Nucleus transcription regulator down 0.01 -1.05 1.01 ILMN_1653751 HOPX down 0.02 -0.70 1.01 11745004_x_at HOPX HOP homeobox Nucleus transcription regulator down 0.02 -1.04 1.03 11749980_x_at HOPX HOP homeobox Nucleus transcription regulator down 0.01 -1.04 1.01 11743168_at IDO1 indoleamine 2,3-dioxygenase 1 Cytoplasm enzyme up 0.01 1.80 1.06 ILMN_1656310 IDO1 up 0.00 0.59 1.14 IDO1 22355111 IDO1 limits innate and adaptive immunity to apoptotic self-antigens. IDO1-mediated inhibition of inflammation plays a key role in suppressing systemic autoimmune diseases. (Demonstrated in mice) 11719491_a_at IFI35 interferon-induced protein 35 Nucleus other up 0.00 1.19 0.89 ILMN_1745374 IFI35 up 0.00 1.19 0.77 11719492_s_at IFI35 interferon-induced protein 35 Nucleus other up 0.00 1.09 0.83 11734541_a_at IL5RA interleukin 5 receptor, alpha Plasma Membrane transmembrane receptor up 0.00 1.53 0.87 ILMN_1756455 IL5RA up 0.00 0.47 1.00 18332133 IRF5 is activated by both TBK1 and MYD88 to form a homodimer that binds to and activates transcription of type I interferon and inflammatory cytokine genes. 11753566_a_at IL5RA interleukin 5 receptor, alpha Plasma Membrane transmembrane receptor up 0.00 1.37 0.99 12600985 IRF5 can act as both an activator and a repressor of interferon (IFN) gene induction dependent on the IRF-interacting partner, and may be a part of the regulatory network that ensures timely expression of the immediate early inflammatory genes. 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator up 0.00 1.94 0.25 ILMN_1670576 IRF5 up 0.00 0.72 0.18 IRF5 22412986 Phosphorylation of IRF5 at ser451 and ser462 is the primary trigger of IRF5 function in nuclear accumulation, transcription and apoptosis. 11718916_a_at IRF7 interferon regulatory factor 7 Nucleus transcription regulator up 0.05 0.66 0.14 ILMN_1798181 IRF7 up 0.00 0.66 0.12 IRF7 19152337 IRF7 increases the expression of a broad range of IFN-stimulated genes including immunomodulatory cytokines and genes involved in antigen processing and presentation. 11716895_s_at ISG15 ISG15 ubiquitin-like modifier Extracellular Space other up 0.03 1.43 0.18 ILMN_1813289 ISG15 up 0.00 1.65 0.37 ISG15 15664995 IRF7 is activated in response to virus infection and stimulates the transcription of a set of cellular genes involved in host antiviral defence. 11719292_a_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other down 0.01 -0.64 1.03 ILMN_1690099 ITGB1BP1 up 0.03 0.41 1.02 15361868 IRF7 forms a complex with MYD88 and TRAF6 and this complex formation, as well as TRAF6-dependent IRF7 ubiquitination, is required for TLR-mediated interferon (IFN)-alpha induction. 11719293_s_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other down 0.01 -0.72 1.03 ILMN_1665107 ITGB1BP1 down 0.00 -0.50 1.01 21820332 IRF7 is involved in the innate immune recognition of Plasmodium falciparum AT-rich DNA and in the subsequent induction of type I IFNs. Mice lacking Irf3/Irf7 are resistant to otherwise lethal cerebral malaria. (Demonstrated in mouse) 11727609_at KLRB1 killer cell lectin-like receptor subfamily B, member 1 Plasma Membrane transmembrane receptor down 0.03 -0.93 1.05 ILMN_1789628 KLRB1 down 0.01 -0.68 1.06 19043203 ISG15 (ISGylation) post-translational modification is mediated by a sequential reaction similar to ubiquitination and has been shown to negatively regulate the NF-kappaB pathway. 11740451_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.03 -0.97 1.05 ILMN_1799134 KLRD1 down 0.02 -0.67 1.09 22022264 ISG15 expression is induced during a hepatitis C virus infection in an IRF3-dependent manner. ISG15 acts as a negative modulator of the RIG-I pathway by mediating the level of DDX58 (RIG-I) ubiquitination. 11742216_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.00 -0.95 1.05 11753534_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.00 -0.88 1.05 11721243_a_at LAP3 leucine aminopeptidase 3 Cytoplasm peptidase up 0.01 0.66 0.43 ILMN_1683792 LAP3 up 0.01 0.67 0.24 11730656_a_at LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), memberExtracellular 3 Space other down 0.00 -1.02 0.10 ILMN_1661631 LILRA3 down 0.00 -0.86 0.19 11738698_x_at LILRA5 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 5 Membrane other up 0.01 1.33 0.71 ILMN_1726545 LILRA5 up 0.00 0.48 0.92 11738903_a_at LILRA5 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 5 Membrane other up 0.00 1.35 0.88 11742375_a_at LILRA5 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 5 Membrane other up 0.00 1.42 0.66 11715461_at LYZ lysozyme Extracellular Space enzyme up 0.02 0.03 0.16 ILMN_1815205 LYZ up 0.04 0.15 0.34 11718659_x_at MOV10 Mov10, Moloney leukemia virus 10, homolog (mouse) Nucleus enzyme up 0.04 0.64 1.04 ILMN_1725700 MOV10 up 0.00 0.56 1.07 MOV10 23093941 MOV10 associates with LINE1 ribonucleoprotein particles and restricts endogenous retrovirus transposition. 11729192_a_at MYNN myoneurin Nucleus transcription regulator down 0.04 -1.04 1.05 ILMN_1672287 MYNN down 0.01 -0.70 1.02 11729193_s_at MYNN myoneurin Nucleus transcription regulator down 0.03 -1.01 1.02 11715858_s_at NCKAP1 NCK-associated protein 1 Plasma Membrane other down 0.01 -0.93 1.02 ILMN_1747392 NCKAP1 down 0.01 -0.35 1.02 11718026_a_at NCOA7 nuclear receptor coactivator 7 Nucleus transcription regulator up 0.02 0.60 0.86 ILMN_1687768 NCOA7 up 0.01 0.35 0.74 11758717_x_at NDUFA4 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDa Cytoplasm enzyme down 0.04 -1.10 1.06 ILMN_1751258 NDUFA4 down 0.02 -1.31 1.09 11761655_at NPCDR1 nasopharyngeal carcinoma, down-regulated 1 unknown other up 0.01 1.22 1.08 ILMN_1780774 NPCDR1 up 0.00 0.66 1.02 11727032_a_at NSG1 neuron specific gene family member 1 Cytoplasm other down 0.04 -0.60 0.25 ILMN_1772627 NSG1 updown 0.05 0.00 0.20 -0.57 0.08 0.12 11743423_a_at NSG1 neuron specific gene family member 1 Cytoplasm other down 0.03 -0.54 0.15 11748198_a_at NSG1 neuron specific gene family member 1 Cytoplasm other down 0.00 -0.81 0.16 21190483 OAS1 is a pathogen recognition receptor for the viral pathogen-associated molecular pattern, double-stranded RNA. Upon recognition of dsRNA, the OAS1 activates RNASEL to cleave ssRNA. The OAS/RNASEL pathway triggers the RIG-I pathway and induce IFNB production. 11724255_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme up 0.05 1.30 0.08 ILMN_1675640 OAS1 up 0.04 1.10 0.10 OAS1 23319625 OAS1 is a cytoplasmic dsRNA sensor. ILMN_1658247 OAS1 up 0.03 1.09 0.09 11726778_at OAS2 2-5-oligoadenylate synthetase 2, 69/71kDa Cytoplasm enzyme up 0.00 0.84 0.14 ILMN_1812740 OAS2 up 0.02 0.38 0.18 OAS2 21190483 OAS2 is a pathogen recognition receptor for the viral pathogen-associated molecular pattern, double-stranded RNA. Upon recognition of dsRNA, the OAS2 activates RNASEL to cleave ssRNA. The OAS/RNASEL pathway triggers the RIG-I pathway and induce IFNB production. 11736134_a_at OAS2 2-5-oligoadenylate synthetase 2, 69/71kDa Cytoplasm enzyme up 0.03 0.89 0.61 11736136_s_at OAS2 2-5-oligoadenylate synthetase 2, 69/71kDa Cytoplasm enzyme up 0.05 0.72 0.59 11721241_at OLIG1 oligodendrocyte transcription factor 1 Nucleus transcription regulator up 0.01 1.15 1.08 ILMN_1666089 OLIG1 up 0.00 0.62 1.10 11736090_a_at OLIG2 oligodendrocyte lineage transcription factor 2 Nucleus transcription regulator up 0.00 1.70 0.97 ILMN_1727567 OLIG2 up 0.00 1.04 0.94 11727757_at OSM oncostatin M Extracellular Space cytokine up 0.02 1.06 0.80 ILMN_1780546 OSM up 0.00 0.90 0.14 21131187 PML, a member of the TRIM protein family, is upregulated by Type I and Type II interferons and have been found to restrict viral replication by modulating the RIG-I pathway. 11726876_a_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.02 0.77 1.07 ILMN_1728019 PML up 0.02 0.53 0.83 PML 21779477 Pml(-/-) mice are resistant to LPS-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-kB pathway. Pml(-/-) mice also exhibit impaired function of macrophages and are thus unable to clear pathogenic microorganisms. (Demonstrated in murine model) 11728557_s_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.03 0.64 0.80 ILMN_1812884 PML up 0.03 0.37 0.79 11751251_a_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.02 0.69 0.97 11715585_a_at PMP22 peripheral myelin protein 22 Plasma Membrane other up 0.00 1.17 1.08 ILMN_1785646 PMP22 up 0.00 0.84 1.10 11738349_x_at POMZP3 POM121 and ZP3 fusion Nucleus other up 0.01 0.83 1.07 ILMN_1709800 POMZP3 up 0.00 0.22 1.05 11718766_at PRSS23 protease, serine, 23 Extracellular Space peptidase down 0.01 -1.43 0.42 ILMN_1797776 PRSS23 down 0.03 -0.53 1.11 11731941_at PRSS33 protease, serine, 33 Extracellular Space peptidase up 0.02 1.79 0.88 ILMN_1736831 PRSS33 up 0.00 1.13 0.75 11736667_a_at PTER phosphotriesterase related unknown enzyme down 0.00 -0.81 0.59 ILMN_1795336 PTER down 0.02 -0.36 0.82 11728067_at PTGDR2 prostaglandin D2 receptor 2 Plasma Membrane G-protein coupled receptor up 0.00 1.33 1.04 ILMN_1703326 PTGDR2 up 0.00 0.98 1.12 11730227_at QRSL1 glutaminyl-tRNA synthase (glutamine-hydrolyzing)-like 1 Cytoplasm enzyme up 0.00 1.37 1.07 ILMN_1733364 QRSL1 up 0.04 0.25 1.02 11725237_a_at RBPMS2 RNA binding protein with multiple splicing 2 unknown other up 0.01 1.43 1.07 ILMN_1808238 RBPMS2 up 0.02 0.72 1.13 11729772_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme up 0.04 1.04 0.72 ILMN_1730628 RNASE2 up 0.00 0.77 0.73 11755743_a_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme up 0.05 1.11 0.73 11735079_at RNASE3 ribonuclease, RNase A family, 3 Cytoplasm enzyme up 0.02 1.01 0.33 ILMN_1802867 RNASE3 up 0.00 0.24 0.10 11718988_s_at RNASE4 ribonuclease, RNase A family, 4 Extracellular Space enzyme down 0.01 -0.82 1.06 ILMN_1776602 RNASE4 down 0.03 -0.40 1.08 11741447_s_at RNASE4 ribonuclease, RNase A family, 4 Extracellular Space enzyme down 0.04 -0.81 1.03 11733014_a_at RNF213 ring finger protein 213 Plasma Membrane enzyme up 0.05 0.78 1.06 ILMN_1674891 RNF213 up 0.01 0.32 1.04 11754353_x_at RNF213 ring finger protein 213 Plasma Membrane enzyme up 0.03 0.78 0.71 ILMN_1749722 RNF213 up 0.03 0.99 0.22 11719784_x_at RPS23 ribosomal protein S23 Cytoplasm translation regulator down 0.01 -0.91 1.03 ILMN_1772459 RPS23 down 0.00 -0.90 1.04 11758816_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.03 -0.94 0.53 ILMN_1656521 RRP7A down 0.04 -0.28 1.08 11758817_x_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.01 -0.72 0.56 11758818_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.01 -0.95 1.02 11758819_x_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.02 -0.87 0.99 11739217_a_at RSAD2 radical S-adenosyl methionine domain containing 2 Cytoplasm enzyme up 0.02 2.30 0.05 ILMN_1657871 RSAD2 up 0.01 1.83 0.06 RSAD2 20308629 RSAD2 (viperin) is an antiviral protein whose expression is highly upregulated during viral infections via IFN-dependent and/or IFN-independent pathways and an IRF1 mediated type I IFN independent mechanism of enhanced RSAD2 expression provides a redundant mechanism to protect cells from viral infections. 11717539_at RYBP RING1 and YY1 binding protein Nucleus transcription regulator up 0.02 0.83 0.99 ILMN_1721842 RYBP up 0.04 0.62 1.12 11720255_a_at SEPT4 septin 4 Cytoplasm enzyme up 0.05 1.17 0.33 ILMN_1776157 SEPT4 up 0.00 0.62 0.43 11720256_x_at SEPT4 septin 4 Cytoplasm enzyme up 0.01 1.13 0.67 11745226_a_at SEPT4 septin 4 Cytoplasm enzyme up 0.00 1.28 0.73 11745227_x_at SEPT4 septin 4 Cytoplasm enzyme up 0.03 0.94 0.52 11730128_a_at SETD9 SET domain containing 9 unknown other down 0.00 -1.05 1.05 ILMN_1757636 SETD9 down 0.01 -0.38 1.00 11720187_a_at SLC27A3 solute carrier family 27 (fatty acid transporter), member 3 Cytoplasm transporter up 0.01 0.85 1.07 ILMN_1719627 SLC27A3 up 0.00 0.77 1.04 11717162_a_at SLC29A1 solute carrier family 29 (nucleoside transporters), member 1 Plasma Membrane transporter up 0.00 1.13 1.08 ILMN_1723971 SLC29A1 up 0.00 0.78 1.04 16451196 SOCS1 is a potent and multifaceted regulator of cytokines and cell-mediated inflammation. 11726509_at SMPD3 sphingomyelin phosphodiesterase 3, neutral membrane (neutral sphingomyelinaseCytoplasm II) enzyme up 0.05 0.99 0.92 ILMN_1802316 SMPD3 up 0.01 0.33 1.13 19017994 SOCS1 regulates the IFN but Not NF{kappa}B Pathway in TLR-Stimulated Human monocytes and macrophages. 11737146_a_at SOCS1 suppressor of cytokine signaling 1 Cytoplasm other up 0.03 0.51 0.91 ILMN_1774733 SOCS1 up 0.01 0.37 1.01 SOCS1 21263070 SOCS1 is a negative immunomodulator that is upregulated by Hepatitis C virus to deliver negative signalling to TLR-mediated pathways controlling expression of IL12, a key cytokine linking innate and adaptive immunity. 11736145_a_at SPATA20 spermatogenesis associated 20 unknown other down 0.00 -0.84 1.03 ILMN_1687247 SPATA20 down 0.00 -0.31 1.10 21606371 SOCS1 is targeted by endogenous and pharmacologic glucocorticoids to limit TLR3/TLR4-mediated STAT1 activation which results in the suppression of inflammation. (Demonstrated in murine model) 11719364_a_at SPATS2L spermatogenesis associated, serine-rich 2-like unknown other up 0.03 1.03 0.14 ILMN_1683678 SPATS2L up 0.01 0.60 0.06 21757742 SOCS1 inhibits type I interferon (IFN) signaling through an interaction with the IFNAR1 associated kinase, TYK2, resulting in a reduced IFN response and reduced IFNAR1 surface expression. 11736293_a_at SPATS2L spermatogenesis associated, serine-rich 2-like unknown other up 0.01 0.90 0.44 11744190_a_at SPNS3 spinster homolog 3 (Drosophila) unknown other up 0.01 0.92 1.06 ILMN_1668984 SPNS3 up 0.04 0.40 0.82 11744191_x_at SPNS3 spinster homolog 3 (Drosophila) unknown other up 0.02 1.02 1.05 11746362_x_at SPNS3 spinster homolog 3 (Drosophila) unknown other up 0.01 0.98 1.08 15069060 TLR5 engagement with its ligand, flagellin, results in the activation of MAP kinases (ERK1/2, JNK, and p38) and degradation of NFKBIA (I-kappa-B-alpha). 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter up 0.05 0.70 0.73 ILMN_1759250 TAP2 up 0.04 0.33 1.01 17283206 Toll-like receptor 5 (TLR5) is the TLR activated by bacterial flagellin and TLR5 residue 268 is responsible for human and mouse discrimination between flagellin molecules. 11723525_at TBC1D8 TBC1 domain family, member 8 (with GRAM domain) Plasma Membrane other up 0.02 0.73 0.76 ILMN_1735495 TBC1D8 up 0.00 0.49 0.60 11323673 TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and its activation mobilizes the nuclear factor NF-kappaB and stimulates tumour necrosis factor-alpha (TNF) production. 11731200_a_at TLR5 toll-like receptor 5 Plasma Membrane transmembrane receptor up 0.05 0.91 0.62 ILMN_1722981 TLR5 up 0.00 0.89 0.69 TLR5 11489966 TLR5 expressed on the basolateral surface of intestinal epithelia mediates innate immune inflammatory responses to Salmonella by inducing epithelial pro-inflammatory gene expression. 11720217_a_at TMEM176A transmembrane protein 176A unknown other up 0.00 0.93 0.70 ILMN_1791511 TMEM176A up 0.00 0.87 0.08 12794153 TLR5 forms heteromeric complexes with TLR4 as well as homomeric complexes. Signaling via heteromeric TLR5/TLR4 complexes is involved in the induction of macrophage nitric oxide (NO) production by Gram-negative flagellin. 11719871_a_at TMEM176B transmembrane protein 176B unknown other up 0.01 0.79 0.39 ILMN_1847047 TMEM176B up 0.03 0.26 0.96 22434932 TLR5 forms a dimer upon binding to bacterial flagellin. 11736522_a_at TNNT1 troponin T type 1 (skeletal, slow) Cytoplasm other up 0.02 1.22 0.88 ILMN_1717297 TNNT1 up 0.00 0.52 0.56 22545147 TLR5 is highly expressed in mucosal dendritic cells and TLR5 signalling restricts regulatory T cell generation. (Demonstrated in mice) 11738247_a_at TNNT1 troponin T type 1 (skeletal, slow) Cytoplasm other up 0.01 1.20 0.98 22863420 TLR5 deficiency in mice leads to a transient inability to manage proteobacteria which promotes chronic gut inflammation. (Demonstrated in mouse) 11755284_s_at TSPAN13 tetraspanin 13 Plasma Membrane other down 0.05 -0.98 1.04 ILMN_1669881 TSPAN13 down 0.01 -0.66 1.07 11730785_a_at TTC21A tetratricopeptide repeat domain 21A Extracellular Space other up 0.04 0.60 1.05 ILMN_1715332 TTC21A up 0.03 0.27 1.05 11730895_at UBA6 ubiquitin-like modifier activating enzyme 6 Cytoplasm enzyme down 0.02 -0.79 1.04 ILMN_1675085 UBA6 down 0.04 -0.49 0.85 11726286_a_at WARS tryptophanyl-tRNA synthetase Cytoplasm enzyme up 0.05 0.85 1.07 ILMN_1727271 WARS up 0.03 0.91 1.10 11747666_a_at WARS tryptophanyl-tRNA synthetase Cytoplasm enzyme up 0.03 0.98 0.80 11732665_a_at VSTM1 V-set and transmembrane domain containing 1 unknown other up 0.02 0.99 1.07 ILMN_1763455 VSTM1 up 0.00 0.84 1.11 11721521_at ZDHHC17 zinc finger, DHHC-type containing 17 Cytoplasm enzyme down 0.04 -0.86 1.01 ILMN_1697153 ZDHHC17 down 0.00 -0.84 1.07 11728584_s_at ZMAT1 zinc finger, matrin-type 1 Nucleus other down 0.04 -1.13 1.02 ILMN_1661010 ZMAT1 down 0.03 -0.31 1.00 11728415_s_at ZP3 zona pellucida glycoprotein 3 (sperm receptor) Extracellular Space transporter up 0.00 1.22 0.95 ILMN_1805377 ZP3 up 0.00 0.50 0.57 11732223_x_at ZP3 zona pellucida glycoprotein 3 (sperm receptor) Extracellular Space transporter up 0.05 0.66 1.07 Page 75 of 111 Diabetes

Differentially regulated genes in seroconverted cases (first sheet) were analyzed with DAVID pathway analysis tool. Pathways (BBID, BioCarta, KEGG, Panther, Reactome) with FDR <20% are reported.

Up-regulation Category Term Count % PValue Genes List Total Pop Hits Pop Total Fold Enrichment Bonferroni Benjamini FDR KEGG_PATHWAY hsa04622:RIG-I-like receptor signaling pathway 4 5.63 0.004813827 DDX58, ISG15, IRF7, DHX58 26 71 5085 11.0184182 0.151313413 0.151313413 4.154758047

Down-regulation No significant findings

Up- or down-regulation Category Term Count % PValue Genes List Total Pop Hits Pop Total Fold Enrichment Bonferroni Benjamini FDR KEGG_PATHWAY hsa04622:RIG-I-like receptor signaling pathway 4 3.64 0.012402365 DDX58, ISG15, IRF7, DHX58 36 71 5085 7.957746479 0.464200808 0.464200808 11.32562991 KEGG_PATHWAY hsa04612:Antigen processing and presentation 4 3.64 0.018850861 TAP2, HLA-A, KLRD1, HLA-DQA1 36 83 5085 6.807228916 0.613854169 0.378593666 16.74763238 REACTOME_PATHWAY REACT_6900:Signaling in Immune system 5 4.55 0.02499627 HLA-A, CD160, TLR5, KLRD1, HLA-DQA1 15 286 3398 3.96037296 0.261967777 0.261967777 15.02914814 PANTHER_PATHWAY P00031:Inflammation mediated by chemokine and cytokine signaling pathway 5 4.55 0.031159972 C3AR1, ALOX15, CCR6, C21ORF7, CCL8 13 304 2857 3.614625506 0.378013293 0.378013293 19.75532044 Diabetes Page 76 of 111

Differentially regulated genes in seroconverted individuals (first sheet) were analyzed through MSig database for enriched transcription factor binding sites on their promoters ( ±±±2 kb around the transcription start site). Motifs with p value < 0.05 are reported.

Enriched motif Motif sequence Transcription factor # Genes annotated to motif (K) # Overlapping input genes (k) k/K p value Genes Up-regulated genes V$IRF_Q6 BNCRSTTTCANTTYY IRF1 242 8 0.0331 0.000033 BST2 ISG15 BATF2 MOV10 OSM SOCS1 IFI35 ADORA3 V$ISRE_01 CAGTTTCWCTTTYCC STAT1&STAT2 247 7 0.0283 0.000274 BST2 ISG15 BATF2 MOV10 OSM DDX58 PML V$IRF7_01 TNSGAAWNCGAAANTNNN IRF7 252 7 0.0278 0.000309 BST2 ISG15 BATF2 MOV10 OSM SOCS1 DDX58 STTTCRNTTT_V$IRF_Q6 STTTCRNTTT no match 188 6 0.0319 0.000410 BST2 ISG15 BATF2 MOV10 OSM DDX58 V$ICSBP_Q6 RAARTGAAACTG IRF8 248 6 0.0242 0.001730 BST2 ISG15 BATF2 MOV10 SOCS1 IFI35 V$IRF2_01 GAAAAGYGAAASY IRF2 125 3 0.0240 0.026800 BST2 OSM DDX58

Down-regulated genes V$FXR_IR1_Q6 GGGTBAATRACCY RXRA 112 2 0.0179 0.026500 SPATA20 RNASE4

Up- or down-regulated genes V$IRF_Q6 BNCRSTTTCANTTYY IRF1 242 8 0.0331 0.000536 BST2 ISG15 BATF2 MOV10 OSM SOCS1 IFI35 ADORA3 V$ISRE_01 CAGTTTCWCTTTYCC STAT1&STAT2 247 7 0.0283 0.002890 BST2 ISG15 BATF2 MOV10 OSM DDX58 PML STTTCRNTTT_V$IRF_Q6 STTTCRNTTT no match 188 6 0.0319 0.003220 BST2 ISG15 BATF2 MOV10 OSM DDX58 V$IRF7_01 TNSGAAWNCGAAANTNNN IRF7 252 7 0.0278 0.003220 BST2 ISG15 BATF2 MOV10 OSM SOCS1 DDX58 V$ICSBP_Q6 RAARTGAAACTG IRF8 248 6 0.0242 0.012000 BST2 ISG15 BATF2 MOV10 SOCS1 IFI35

No match = Motif does not match any known transcription factor Page 77 of 111 Diabetes

Differentially expressed genes in T1D progressors (FDR < 0.05) showing concordant changes in Affymetrix and Illumina arrays, and information regarding the innate immunity function of the genes (InnateDB)

AFFYMETRIX Case vs. control Control vs. case ILLUMINA Case vs. control Control vs. case InnateDB (www.innatedb.org) Innate Immunity Genes in human. P value for overlap is 0.0000013. Affymetrix ID Gene Symbol (IPA) Gene name (IPA) Location (IPA) Type (IPA) Drug (IPA) Change probeset FDR max FDR min SLR max SLR min FDR max FDR min Illumina ID Gene Symbol (IPA) Change probe FDR max FDR min SLR max SLR min FDR max FDR min Gene Symbol Pubmed(human) ID Annotation 11739503_at ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1 Plasma Membrane transporter down 0.03 -0.72 1.16 ILMN_1766054 ABCA1 down 0.00 -0.73 1.21 ABCA1 20650929 ABCA1 in macrophages dampens inflammation by reducing MYD88-dependent TLR trafficking to lipid rafts, thus selectively reducing free cholesterol content in lipid rafts. 11724634_s_at ABCB10 ATP-binding cassette, sub-family B (MDR/TAP), member 10 Cytoplasm transporter down 0.02 -0.49 1.00 ILMN_1665730 ABCB10 down 0.02 -0.42 0.20 22955730 ABCA1 deletion in the myeloid lineage enhances host immune response and clearance of Listeria monocytogenes. (Demonstrated in mice) 11730238_a_at ABHD10 abhydrolase domain containing 10 Cytoplasm enzyme down 0.00 -0.87 0.91 ILMN_1770031 ABHD10 down 0.05 -0.30 0.65 11720859_s_at ABHD3 abhydrolase domain containing 3 unknown enzyme down 0.00 -0.62 1.10 ILMN_1801767 ABHD3 down 0.00 -0.51 1.18 11746269_a_at ABHD3 abhydrolase domain containing 3 unknown enzyme down 0.01 -0.78 1.14 11726322_at ACOX1 acyl-CoA oxidase 1, palmitoyl Cytoplasm enzyme down 0.02 -0.58 1.09 ILMN_1750158 ACOX1 down 0.01 -0.39 1.21 11726323_a_at ACOX1 acyl-CoA oxidase 1, palmitoyl Cytoplasm enzyme down 0.01 -0.81 1.16 11750711_a_at ACOX1 acyl-CoA oxidase 1, palmitoyl Cytoplasm enzyme down 0.02 -0.81 1.17 11716710_a_at ADM adrenomedullin Extracellular Space other down 0.00 -0.87 0.86 ILMN_1708934 ADM down 0.00 -0.50 0.66 11756406_x_at ADM adrenomedullin Extracellular Space other down 0.00 -0.84 1.11 19158675 AIM2 recognizes cytosolic double stranded DNA and forms a caspase-1-activating inflammasome with PYCARD (ASC). 11754726_a_at AGGF1 angiogenic factor with G patch and FHA domains 1 Cytoplasm other down 0.04 -0.47 1.08 ILMN_2064917 AGGF1 down 0.02 -0.30 1.22 20351693 AIM2 has a critical role in host innate immunity to intracellular pathogens where it is a crucial sensor of F. tularensis infection. 11730253_a_at AHCTF1 AT hook containing transcription factor 1 Nucleus transcription regulator down 0.00 -0.63 1.16 ILMN_1809139 AHCTF1 down 0.00 -0.55 1.09 20351692 AIM2 inflammasome is essential for host defence against cytosolic bacteria and DNA viruses. 11730457_a_at AIM2 absent in melanoma 2 Cytoplasm other up 0.00 1.06 0.06 ILMN_1681301 AIM2 up 0.00 0.61 0.06 AIM2 20401524 AIM2 is a newly discovered pattern recognition receptor (PRR) involved in the sensing of dangerous cytosolic DNA produced by infection with DNA viruses. 11722671_at AKAP11 A kinase (PRKA) anchor protein 11 Cytoplasm other down 0.02 -0.72 0.88 ILMN_2293758 AKAP11 down 0.04 -0.46 0.59 20457908 AIM2 is required for innate immune recognition of Francisella tularensis where AIM2-deficient mice display an increased susceptibility to F. tularensis infection compared with wild-type mice. 11741283_a_at AKAP7 A kinase (PRKA) anchor protein 7 Plasma Membrane other down 0.04 -0.59 1.16 ILMN_1733690 AKAP7 down 0.00 -0.56 0.11 21562230 AIM2-containing inflammasomes are activated in response to cytosolic DNA, Â this response is augmented in keratinocytes from psoriatic lesions and contributes to the auto-inflammatory disease. 11735362_s_at AKTIP AKT interacting protein Cytoplasm other down 0.04 -0.38 1.09 ILMN_2377240 AKTIP down 0.00 -0.41 0.97 11716182_s_at ALCAM activated leukocyte cell adhesion molecule Plasma Membrane other down 0.00 -0.71 1.16 ILMN_1670870 ALCAM down 0.00 -0.54 1.20 11716184_s_at ALCAM activated leukocyte cell adhesion molecule Plasma Membrane other down 0.00 -0.89 1.13 11716186_s_at ALCAM activated leukocyte cell adhesion molecule Plasma Membrane other down 0.00 -0.64 1.15 11743044_a_at ALDH1A1 aldehyde dehydrogenase 1 family, member A1 Cytoplasm enzyme disulfiram, chlorpropamideup 0.03 0.70 0.50 ILMN_2096372 ALDH1A1 up 0.03 0.28 0.09 11752548_a_at ALDH1A1 aldehyde dehydrogenase 1 family, member A1 Cytoplasm enzyme disulfiram, chlorpropamideup 0.01 0.67 0.68 ILMN_1709348 ALDH1A1 up 0.00 0.46 0.42 11752549_x_at ALDH1A1 aldehyde dehydrogenase 1 family, member A1 Cytoplasm enzyme disulfiram, chlorpropamideup 0.02 0.68 0.59 11737650_at ANKFY1 ankyrin repeat and FYVE domain containing 1 Nucleus transcription regulator up 0.01 0.91 0.90 ILMN_1801464 ANKFY1 up 0.02 0.33 1.18 11721746_x_at ANKRD12 ankyrin repeat domain 12 Nucleus other down 0.01 -0.70 1.15 ILMN_1661833 ANKRD12 down 0.00 -0.45 1.22 11721747_a_at ANKRD12 ankyrin repeat domain 12 Nucleus other down 0.00 -0.72 1.01 11757991_s_at ANKRD12 ankyrin repeat domain 12 Nucleus other down 0.00 -0.66 1.14 11757989_s_at ANKRD46 ankyrin repeat domain 46 Nucleus transcription regulator down 0.02 -0.76 1.09 ILMN_1712298 ANKRD46 down 0.01 -0.55 0.24 11724283_a_at ANXA3 annexin A3 Cytoplasm enzyme down 0.00 -1.72 1.16 ILMN_1694548 ANXA3 down 0.04 -0.46 1.16 11756334_x_at ANXA3 annexin A3 Cytoplasm enzyme down 0.00 -1.69 1.17 11727629_at APBA2 amyloid beta (A4) precursor protein-binding, family A, member 2 Cytoplasm transporter up 0.01 0.66 1.17 ILMN_1723626 APBA2 up 0.00 0.47 1.01 11727630_s_at APBA2 amyloid beta (A4) precursor protein-binding, family A, member 2 Cytoplasm transporter up 0.01 0.53 1.16 11727631_s_at APBA2 amyloid beta (A4) precursor protein-binding, family A, member 2 Cytoplasm transporter up 0.01 0.49 1.09 11725701_a_at AQP9 aquaporin 9 Plasma Membrane transporter down 0.00 -1.06 1.16 ILMN_1715068 AQP9 down 0.00 -0.63 0.61 11749906_a_at AQP9 aquaporin 9 Plasma Membrane transporter down 0.00 -1.00 1.06 11730207_at ARAP2 ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2 Cytoplasm other down 0.05 -0.47 1.15 ILMN_1709360 ARAP2 down 0.02 -0.43 0.52 11718702_a_at ARFIP1 ADP-ribosylation factor interacting protein 1 Cytoplasm other down 0.00 -0.55 1.07 ILMN_2403906 ARFIP1 down 0.00 -0.33 1.20 11736113_at ARHGAP18 Rho GTPase activating protein 18 Cytoplasm other down 0.04 -0.57 1.04 ILMN_1791186 ARHGAP18 down 0.00 -0.35 1.04 11749323_a_at ARHGAP25 Rho GTPase activating protein 25 Cytoplasm other down 0.05 -0.55 1.12 ILMN_1777998 ARHGAP25 down 0.01 -0.44 0.38 11740704_a_at ARID4A AT rich interactive domain 4A (RBP1-like) Nucleus transcription regulator down 0.02 -0.53 1.17 ILMN_1810229 ARID4A down 0.00 -0.42 1.19 11743712_a_at ARID4A AT rich interactive domain 4A (RBP1-like) Nucleus transcription regulator down 0.00 -0.68 1.17 11743713_x_at ARID4A AT rich interactive domain 4A (RBP1-like) Nucleus transcription regulator down 0.00 -0.61 1.15 11743714_a_at ARID4A AT rich interactive domain 4A (RBP1-like) Nucleus transcription regulator down 0.00 -0.58 1.07 11758442_s_at ARID4A AT rich interactive domain 4A (RBP1-like) Nucleus transcription regulator down 0.00 -0.66 1.17 11742838_at ARRB1 arrestin, beta 1 Cytoplasm other down 0.03 -0.63 1.16 ILMN_2325168 ARRB1 down 0.01 -0.38 1.12 ILMN_1730620 ARRB1 down 0.02 -0.42 1.18 11729871_a_at ASGR2 asialoglycoprotein receptor 2 Plasma Membrane transmembrane receptor up 0.02 0.66 0.71 ILMN_1694966 ASGR2 up 0.01 0.44 1.07 11729306_s_at ATAD1 ATPase family, AAA domain containing 1 Cytoplasm enzyme down 0.05 -0.60 0.60 ILMN_1654497 ATAD1 down 0.03 -0.39 0.70 11754241_a_at ATAD1 ATPase family, AAA domain containing 1 Cytoplasm enzyme down 0.00 -0.66 1.16 11717800_a_at ATF5 activating transcription factor 5 Nucleus transcription regulator up 0.00 0.94 1.10 ILMN_1669113 ATF5 up 0.00 0.43 0.79 11717801_a_at ATF5 activating transcription factor 5 Nucleus transcription regulator up 0.00 0.71 1.13 11754592_x_at ATF5 activating transcription factor 5 Nucleus transcription regulator up 0.02 0.55 1.12 11715890_x_at ATP5I ATP synthase, H+ transporting, mitochondrial Fo complex, subunit E Cytoplasm transporter up 0.03 0.61 1.16 ILMN_1726603 ATP5I up 0.00 0.47 0.69 11728909_s_at B3GALTL beta 1,3-galactosyltransferase-like unknown other down 0.00 -0.49 0.56 ILMN_1764813 B3GALTL down 0.00 -0.37 0.06 11746692_a_at BAZ1A bromodomain adjacent to zinc finger domain, 1A Nucleus other down 0.01 -0.74 1.16 ILMN_1742230 BAZ1A down 0.00 -0.44 1.21 ILMN_1658327 BAZ1A updown 0.05 0.01 0.40 -0.48 0.41 0.46 11726097_a_at BAZ2B bromodomain adjacent to zinc finger domain, 2B Extracellular Space other down 0.01 -0.66 1.13 ILMN_1720850 BAZ2B down 0.00 -0.56 1.22 11758040_s_at BAZ2B bromodomain adjacent to zinc finger domain, 2B Extracellular Space other down 0.00 -0.69 1.14 11728217_a_at BCLAF1 BCL2-associated transcription factor 1 Nucleus transcription regulator down 0.00 -0.61 1.14 ILMN_2357272 BCLAF1 down 0.00 -0.33 0.15 11728218_a_at BCLAF1 BCL2-associated transcription factor 1 Nucleus transcription regulator down 0.01 -0.57 1.16 11745967_x_at BCLAF1 BCL2-associated transcription factor 1 Nucleus transcription regulator down 0.02 -0.54 1.02 18697935 BIRC2 regulates TNF-alpha(TNF)-mediated NF-kappaB activation by binding to TNFRSF1A (TNF receptor 1). 11758404_s_at BCLAF1 BCL2-associated transcription factor 1 Nucleus transcription regulator down 0.01 -0.55 1.13 17220297 BIRC2 is the ubiquitin protein ligase for ASK1 ubiquitination, a protein that plays an essential role in tumour necrosis factor alpha (TNF-alpha)-induced mitogen-activated protein kinase signalling. BIRC2 is also responsible for regulating the duration of TNF signalling in primary cells expressing TNFR2. 11717627_a_at BIRC2 baculoviral IAP repeat containing 2 Cytoplasm enzyme down 0.02 -0.63 1.09 ILMN_2182704 BIRC2 down 0.00 -0.62 0.79 BIRC2 19464198 BIRC2 and BIRC3 are required for innate immunity signalling by the pattern recognition receptors NOD1 and NOD2. 11744694_a_at BIRC2 baculoviral IAP repeat containing 2 Cytoplasm enzyme down 0.00 -0.68 1.12 20458734 BIRC2 plays a role in lipopolysaccharide (LPS)-induced autophagy in vascular endothelial cells (VECs). 11750887_a_at BIRC2 baculoviral IAP repeat containing 2 Cytoplasm enzyme down 0.00 -0.62 0.98 21447281 BIRC2 facilitates ubiquitin-dependent signalling activated by pattern recognition receptors, such as TLR and NOD, to mediate the activation of NFKB transcription. 11757937_s_at BIRC2 baculoviral IAP repeat containing 2 Cytoplasm enzyme down 0.00 -0.67 1.16 11723670_a_at BNIP2 BCL2/adenovirus E1B 19kDa interacting protein 2 Cytoplasm other down 0.02 -0.48 1.14 ILMN_1770803 BNIP2 down 0.00 -0.46 0.25 11748298_a_at BNIP2 BCL2/adenovirus E1B 19kDa interacting protein 2 Cytoplasm other down 0.02 -0.59 1.04 11728439_at BRWD1 bromodomain and WD repeat domain containing 1 Nucleus transcription regulator down 0.03 -0.63 0.51 ILMN_1805111 BRWD1 down 0.03 -0.49 1.11 11734978_at BTNL3 butyrophilin-like 3 unknown other down 0.00 -1.81 0.09 ILMN_1783795 BTNL3 down 0.00 -0.82 0.28 11736057_s_at C10orf32 chromosome 10 open reading frame 32 unknown other down 0.00 -0.80 1.11 ILMN_2151056 C10orf32 down 0.00 -0.75 0.84 11736058_s_at C10orf32 chromosome 10 open reading frame 32 unknown other down 0.00 -0.92 0.89 11724320_x_at C11orf54 chromosome 11 open reading frame 54 Nucleus other down 0.04 -0.53 1.05 ILMN_2213297 C11orf54 down 0.04 -0.39 1.16 ILMN_1664738 C11orf54 down 0.00 -0.45 1.16 11744178_a_at C19orf66 chromosome 19 open reading frame 66 unknown other up 0.00 0.65 0.71 ILMN_1750400 C19orf66 up 0.00 0.57 0.50 11751202_a_at C19orf66 chromosome 19 open reading frame 66 unknown other up 0.00 0.50 1.12 12791093 C2 is part of the classical and lectin complement pathways 11717045_a_at C2 complement component 2 Extracellular Space peptidase up 0.00 1.08 0.41 ILMN_1710740 C2 up 0.00 0.50 0.68 C2 11044372 C2 molecule binds to C4B and is cleaved by C1S protease into C2A and C2B fragments and the resulting C4B2A complex (C3 convertase) is the active protease which cleaves C3 11738455_a_at C20orf197 chromosome 20 open reading frame 197 unknown other down 0.00 -1.07 1.14 ILMN_1691228 C20orf197 down 0.00 -0.46 1.11 11738456_s_at C20orf197 chromosome 20 open reading frame 197 unknown other down 0.00 -0.91 1.12 11757208_s_at C22orf34 chromosome 22 open reading frame 34 unknown other up 0.02 0.75 1.05 ILMN_1717371 C22orf34 up 0.00 0.58 1.15 ILMN_1911927 C22orf34 up 0.00 0.54 1.16 11734747_a_at C4B (includes others) complement component 4B (Chido blood group) Extracellular Space other down 0.04 -0.54 1.11 ILMN_2179533 C4B (includes others) down 0.04 -0.52 0.34 20159852 C5AR1 engage in crosstalk with TLR2 and Porphyromonas gingivalis, a major oral and systemic pathogen with complement C5 convertase-like activity, synergizes with C5a (fragment of complement protein C5) to increase cyclic adenosine monophosphate (cAMP) concentrations, resulting in suppression of macrophage immune function and enhanced pathogen survival. 11733356_at C5AR1 complement component 5a receptor 1 Plasma Membrane G-protein coupled receptor down 0.00 -0.77 1.17 ILMN_1689836 C5AR1 down 0.00 -0.52 1.03 C5AR1 20457757 C5AR1 is a receptor for C5a, a chief component of complement activation produced via all three complement pathways (i.e., lectin, classical, and alternative), stimulated tissue-resident macrophages, but not dendritic cells, to produce inflammatory cytokines including IL-6, in synergy with Toll-like receptor signalling or, notably, granulocyte/macrophage colony-stimulating factor (GM-CSF). 11730513_a_at C7orf53 chromosome 7 open reading frame 53 unknown other down 0.03 -0.73 1.12 ILMN_1804895 C7orf53 down 0.01 -0.51 1.22 23479227 Increasing circulating C5AR1 serum concentration, coupled with decreased C5AR1 expression on neutrophils is correlated with lethality from septic shock. 11758682_s_at C9orf123 chromosome 9 open reading frame 123 unknown other down 0.01 -0.70 0.79 ILMN_1769409 C9orf123 down 0.01 -0.52 0.27 11720531_at C9orf72 chromosome 9 open reading frame 72 unknown other down 0.01 -0.66 1.17 ILMN_1741881 C9orf72 down 0.00 -0.58 1.04 11720532_s_at C9orf72 chromosome 9 open reading frame 72 unknown other down 0.01 -0.58 1.14 11758239_s_at C9orf72 chromosome 9 open reading frame 72 unknown other down 0.01 -0.84 1.04 11745552_a_at CAB39 calcium binding protein 39 Cytoplasm enzyme down 0.04 -0.51 1.17 ILMN_1765858 CAB39 down 0.00 -0.43 1.13 11731967_a_at CACNA1I calcium channel, voltage-dependent, T type, alpha 1I subunit Plasma Membrane ion channel mibefradil up 0.04 0.43 1.17 ILMN_2300664 CACNA1I up 0.00 0.48 0.45 11723011_s_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.00 -0.78 1.06 ILMN_1768870 CAPZA2 down 0.00 -0.56 0.90 11723012_a_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.00 -0.95 1.16 11723013_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.00 -1.00 1.11 11747046_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.00 -0.93 1.10 11750192_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.00 -0.88 1.16 11727338_a_at CARNS1 carnosine synthase 1 unknown enzyme up 0.00 0.71 1.11 ILMN_1725746 CARNS1 up 0.03 0.39 1.17 11748369_a_at CARNS1 carnosine synthase 1 unknown enzyme up 0.02 0.60 1.10 11717805_a_at CASP3 caspase 3, apoptosis-related cysteine peptidase Cytoplasm peptidase IDN-6556 down 0.00 -1.03 1.17 ILMN_2388155 CASP3 down 0.01 -0.62 1.10 11719838_a_at CASP3 caspase 3, apoptosis-related cysteine peptidase Cytoplasm peptidase IDN-6556 down 0.01 -0.68 1.11 11719839_a_at CASP3 caspase 3, apoptosis-related cysteine peptidase Cytoplasm peptidase IDN-6556 down 0.00 -0.85 1.14 11754530_a_at CCDC14 coiled-coil domain containing 14 Cytoplasm other down 0.01 -0.55 0.92 ILMN_1677239 CCDC14 down 0.04 -0.40 1.13 11728027_x_at CCDC58 coiled-coil domain containing 58 Cytoplasm other up 0.00 0.90 1.07 ILMN_1686920 CCDC58 up 0.00 0.48 1.10 11736416_s_at CCDC82 coiled-coil domain containing 82 unknown other down 0.00 -0.96 1.10 ILMN_1791933 CCDC82 updown 0.02 0.00 0.56 -0.58 0.73 0.93 11744442_at CCDC82 coiled-coil domain containing 82 unknown other down 0.00 -1.04 0.80 19776284 CD14 co-receptor participates with toll-like receptors (TLRs) in the response of microglial cells to fibrillar forms of beta-amyloid, contributing to microglial activation. 11744443_x_at CCDC82 coiled-coil domain containing 82 unknown other down 0.00 -1.05 1.04 19840871 CD14 recognizes necrotic cells in addition to LPS, PG, apoptotic cells, and lipids, suggesting that it might be a universal adaptor for damage-associated molecular pattern (DAMP) and pathogen-associated molecular patterns (PAMP). 11741519_s_at CD14 CD14 molecule Plasma Membrane transmembrane receptor down 0.02 -0.68 1.05 ILMN_2396444 CD14 down 0.00 -0.56 1.07 CD14 10652232 CD14 is a molecule that binds to lipopolysaccharide (LPS) and facilitates its signalling by helping TLR4-LY96 to sense and signal the presence of LPS. 11741520_x_at CD14 CD14 molecule Plasma Membrane transmembrane receptor down 0.03 -0.58 0.94 ILMN_1740015 CD14 down 0.01 -0.60 0.48 21078886 CD14 contributes to nucleic acid uptake in macrophages and acts as a co-receptor for endosomal TLR7/TLR9 activation. 11742099_x_at CD164 CD164 molecule, sialomucin Plasma Membrane other down 0.04 -0.53 1.17 ILMN_1783852 CD164 down 0.03 -0.40 1.21 20087059 CD46 is a cell surface pathogen receptor that induces autophagy upon pathogen recognition and this CD46-dependent autophagy is critical for early control of the infection. 11718971_x_at CD46 CD46 molecule, complement regulatory protein Plasma Membrane other down 0.01 -0.54 1.06 ILMN_2307740 CD46 down 0.00 -0.47 0.36 CD46 15919905 CD46 is a ubiquitously expressed membrane protein that regulates complement activation, as a cellular attachment receptor of several pathogens, including measles virus, Neisseria gonorrhea, adenovirus and human herpesvirus 6. 11720595_a_at CD46 CD46 molecule, complement regulatory protein Plasma Membrane other down 0.01 -0.67 1.17 18573902 CD46 enhances bacterial survival and represents a novel pathogenic mechanism that contributes to the severity of group A streptococcal disease. 11735060_a_at CD46 CD46 molecule, complement regulatory protein Plasma Membrane other down 0.00 -0.72 1.10 16888016 CD46 acts as a human epithelial cell receptor for internalization of opsonized uropathogenic Escherichia coli. 11735681_x_at CD46 CD46 molecule, complement regulatory protein Plasma Membrane other down 0.02 -0.51 1.09 16087667 CD46 plays a key role in tailoring innate immune recognition of apoptotic and necrotic cells, whereby the complement innate immune system is using two synergistic strategies with the recognition of altered self-nucleic acids (NA) and missing self-CD46 signals to instruct and tailor the efficient removal of apoptotic and necrotic cells in immunoprivileged sites. 11743903_a_at CD46 CD46 molecule, complement regulatory protein Plasma Membrane other down 0.00 -0.59 1.10 21488871 CD46 is expressed ubiquitously and functions as a co-factor in the factor I-mediated proteolytic cleavage of C3b and C4b. CD46 has a vital role in preventing complement deposition on host tissue, and the resulting auto-immunity. 11751549_a_at CD46 CD46 molecule, complement regulatory protein Plasma Membrane other down 0.02 -0.71 1.17 11755715_x_at CD46 CD46 molecule, complement regulatory protein Plasma Membrane other down 0.04 -0.64 1.14 11729741_x_at CD68 CD68 molecule Plasma Membrane other up 0.00 0.57 0.22 ILMN_1714861 CD68 up 0.00 0.27 0.25 11750359_x_at CD68 CD68 molecule Plasma Membrane other up 0.00 0.48 0.25 ILMN_2359907 CD68 up 0.00 0.66 0.14 11725576_s_at CDC14A CDC14 cell division cycle 14 homolog A (S. cerevisiae) Nucleus phosphatase down 0.01 -0.71 0.80 ILMN_1774930 CDC14A down 0.01 -0.47 1.17 11717137_s_at CDC42EP4 CDC42 effector protein (Rho GTPase binding) 4 Cytoplasm other down 0.03 -0.67 1.17 ILMN_1745223 CDC42EP4 down 0.00 -0.58 1.22 11734425_a_at CDH23 cadherin-related 23 Plasma Membrane transporter up 0.01 0.54 1.16 ILMN_1783149 CDH23 up 0.01 0.36 0.26 11729676_s_at CDK17 cyclin-dependent kinase 17 Cytoplasm kinase down 0.01 -0.58 0.95 ILMN_1780824 CDK17 down 0.02 -0.47 0.13 11722022_s_at CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35) Nucleus kinase down 0.03 -0.51 1.09 ILMN_1730928 CDK5R1 down 0.01 -0.46 0.21 11751094_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.04 -1.08 1.11 ILMN_1716815 CEACAM1 down 0.01 -0.59 1.21 CEACAM1 18836450 CEACAM1 inhibits TLR2 induced pro-inflammatory immune responses by inducing PTPN6-(SHP-1)-mediated inhibition of the PI3K-NF-kappaB signal transduction pathway in pulmonary epithelial cells. 11762911_x_at CEACAM3 carcinoembryonic antigen-related cell adhesion molecule 3 unknown other down 0.04 -0.67 1.08 ILMN_1743570 CEACAM3 down 0.01 -0.72 0.84 11732601_at CEP135 centrosomal protein 135kDa Cytoplasm other down 0.03 -0.59 0.76 ILMN_1693766 CEP135 down 0.00 -0.34 0.31 11732602_at CEP135 centrosomal protein 135kDa Cytoplasm other down 0.03 -0.56 1.17 11728857_at CEP19 centrosomal protein 19kDa unknown other down 0.00 -0.86 1.13 ILMN_1873107 CEP19 down 0.00 -0.50 1.14 11728858_at CEP19 centrosomal protein 19kDa unknown other down 0.01 -0.58 1.04 11758085_s_at CEP44 centrosomal protein 44kDa Cytoplasm other down 0.02 -0.57 1.11 ILMN_2213199 CEP44 down 0.01 -0.41 0.15 11759323_at CEP85L centrosomal protein 85kDa-like Cytoplasm other down 0.00 -0.80 0.71 ILMN_1855286 CEP85L down 0.00 -0.66 0.52 11759324_s_at CEP85L centrosomal protein 85kDa-like Cytoplasm other down 0.01 -0.70 1.12 11742900_a_at CGGBP1 CGG triplet repeat binding protein 1 Nucleus other down 0.01 -0.50 1.05 ILMN_1752631 CGGBP1 down 0.00 -0.46 0.74 11733638_at CHM choroideremia (Rab escort protein 1) Cytoplasm enzyme down 0.00 -0.95 1.10 ILMN_1771238 CHM down 0.01 -0.42 0.51 11724746_at CHMP2B charged multivesicular body protein 2B Cytoplasm other down 0.01 -0.50 1.09 ILMN_1741176 CHMP2B down 0.01 -0.38 1.17 11724748_at CHMP2B charged multivesicular body protein 2B Cytoplasm other down 0.02 -0.44 1.15 12351658 CHUK is part of the inhibitor kappaB kinase (IKK) complex that phosphorylates IRS1 at Ser(312) and this contributes to the insulin resistance mediated by activation of inflammatory pathways. 11730536_at CHST13 carbohydrate (chondroitin 4) sulfotransferase 13 Cytoplasm enzyme down 0.02 -0.80 0.84 ILMN_1734707 CHST13 down 0.02 -0.44 0.13 9891086 CHUK (IKK-alpha) is part of the IKK signalosome that phosphorylates NFKBIA and NFKBIB, leading to activation of NF-kappaB. 11759834_a_at CHST15 carbohydrate (N-acetylgalactosamine 4-sulfate 6-O) sulfotransferase 15 Plasma Membrane enzyme down 0.00 -0.84 1.10 ILMN_1670926 CHST15 down 0.04 -0.36 0.71 17434128 CHUK (IKKalpha) phosphorylates CREBBP (CBP), regulating the CBP-mediated crosstalk between NF-kappaB and p53, a critical factor in the promotion of cell proliferation and tumor growth. 11754797_a_at CHUK conserved helix-loop-helix ubiquitous kinase Cytoplasm kinase methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oatedown 0.03 -0.46 1.12 ILMN_1677041 CHUK down 0.00 -0.38 1.13 CHUK 20200270 CHUK is a unique molecule involved in TLR7/9-MyD88-dependent type I IFN production through dendritic cell subset-specific mechanisms. 11723678_at CKAP2 cytoskeleton associated protein 2 Cytoplasm other down 0.01 -0.62 0.67 ILMN_1674411 CKAP2 down 0.04 -0.40 0.42 21765415 CHUK has a key role in the negative feedback of NF-kB canonical signalling by orchestrating the assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation in response to proinflammatory stimuli such as TNF and IL1. (Demonstrated in mouse) 11728603_a_at CLDN23 claudin 23 Plasma Membrane other up 0.00 0.93 1.17 ILMN_1725338 CLDN23 up 0.00 0.68 0.42 23422957 CHUK is required in dendritic cells to prime adaptive immunity to Listeria monocytogenes. 11730119_at CLDND2 claudin domain containing 2 unknown other up 0.02 0.44 0.88 ILMN_2077680 CLDND2 up 0.00 0.63 0.43 11729479_a_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other down 0.00 -0.70 0.23 ILMN_2292178 CLEC12A down 0.00 -0.57 0.14 11753241_s_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other down 0.02 -0.77 0.33 11762101_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other down 0.02 -0.74 0.26 11724885_at CLIC3 chloride intracellular channel 3 Nucleus ion channel up 0.00 0.93 0.71 ILMN_1796423 CLIC3 up 0.00 0.54 0.42 11726514_a_at CLK4 CDC-like kinase 4 Nucleus kinase down 0.00 -0.72 0.90 ILMN_1695853 CLK4 down 0.00 -0.60 0.80 11726515_a_at CLK4 CDC-like kinase 4 Nucleus kinase down 0.01 -0.75 1.04 11726516_s_at CLK4 CDC-like kinase 4 Nucleus kinase down 0.02 -0.62 0.64 11728036_a_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.00 0.77 0.90 ILMN_1775373 CMTM5 up 0.00 0.40 1.04 11728037_x_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.00 0.67 0.79 11753119_x_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.03 0.54 0.91 11753465_a_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.01 0.67 0.79 11724049_a_at COG6 component of oligomeric golgi complex 6 Cytoplasm transporter down 0.04 -0.55 0.78 ILMN_1779530 COG6 down 0.00 -0.40 1.17 11716281_a_at COL18A1 collagen, type XVIII, alpha 1 Extracellular Space other collagenase clostridiumdown histolyticum 0.02 -0.55 1.14 ILMN_1806733 COL18A1 down 0.00 -0.50 1.15 11755399_a_at COL18A1 collagen, type XVIII, alpha 1 Extracellular Space other collagenase clostridiumdown histolyticum 0.05 -0.48 1.15 11731849_a_at COLQ collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesteraseExtracellular Space other up 0.04 0.62 1.12 ILMN_1695991 COLQ up 0.01 0.48 1.15 11733495_a_at COMMD6 COMM domain containing 6 unknown other up 0.02 1.31 0.84 ILMN_1777378 COMMD6 up 0.02 0.34 0.66 11733496_x_at COMMD6 COMM domain containing 6 unknown other up 0.01 1.27 0.78 11733497_a_at COMMD6 COMM domain containing 6 unknown other up 0.03 0.84 1.17 11753841_x_at COMMD6 COMM domain containing 6 unknown other up 0.02 1.28 0.87 11756875_x_at COMMD6 COMM domain containing 6 unknown other up 0.02 1.25 0.81 11717634_a_at COX6C cytochrome c oxidase subunit VIc Cytoplasm enzyme up 0.00 1.13 0.75 ILMN_1654151 COX6C up 0.02 0.40 1.16 11754444_x_at COX6C cytochrome c oxidase subunit VIc Cytoplasm enzyme up 0.01 1.21 0.80 11715694_at COX7B cytochrome c oxidase subunit VIIb Cytoplasm enzyme updown 0.03 0.03 1.42 -1.28 1.11 1.00 ILMN_2184049 COX7B updown 0.05 0.03 0.54 -0.56 0.53 1.22 11715695_x_at COX7B cytochrome c oxidase subunit VIIb Cytoplasm enzyme updown 0.02 0.03 1.41 -1.36 1.11 0.93 11735847_a_at CPA5 carboxypeptidase A5 Extracellular Space peptidase up 0.00 0.42 0.54 ILMN_1791530 CPA5 up 0.00 0.17 0.82 11724951_s_at CPEB2 cytoplasmic polyadenylation element binding protein 2 Cytoplasm other down 0.00 -0.80 1.16 ILMN_1774948 CPEB2 down 0.04 -0.48 0.24 ILMN_2375484 CPEB2 down 0.02 -0.50 1.21 11726485_at CPED1 cadherin-like and PC-esterase domain containing 1 Cytoplasm other down 0.00 -1.02 0.52 ILMN_1677038 CPED1 down 0.03 -0.55 1.21 11722970_a_at CREB5 cAMP responsive element binding protein 5 Nucleus transcription regulator down 0.04 -0.53 1.02 ILMN_1731714 CREB5 down 0.01 -0.45 0.28 11739552_a_at CREB5 cAMP responsive element binding protein 5 Nucleus transcription regulator down 0.02 -0.91 0.81 11750879_a_at CREB5 cAMP responsive element binding protein 5 Nucleus transcription regulator down 0.03 -0.87 0.95 11727223_a_at CSGALNACT1 chondroitin sulfate N-acetylgalactosaminyltransferase 1 Cytoplasm enzyme down 0.01 -0.64 0.06 ILMN_2055523 CSGALNACT1 down 0.01 -0.17 0.14 11732526_s_at CSGALNACT1 chondroitin sulfate N-acetylgalactosaminyltransferase 1 Cytoplasm enzyme down 0.01 -0.46 0.10 11732701_a_at CSGALNACT2 chondroitin sulfate N-acetylgalactosaminyltransferase 2 Cytoplasm enzyme down 0.00 -0.60 1.09 ILMN_1799208 CSGALNACT2 down 0.05 -0.42 0.39 11757500_a_at CTDSPL CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase-likeNucleus other up 0.01 0.88 0.61 ILMN_2392189 CTDSPL up 0.04 0.35 0.48 11749005_a_at CTNNA1 catenin (cadherin-associated protein), alpha 1, 102kDa Plasma Membrane other down 0.03 -0.65 1.06 ILMN_1804854 CTNNA1 down 0.02 -0.43 0.93 ILMN_2230902 CTNNA1 down 0.00 -0.52 0.68 11725332_a_at CTSL1 cathepsin L1 Cytoplasm peptidase up 0.01 0.62 0.74 ILMN_1812995 CTSL1 up 0.01 0.38 0.42 CTSL1 20926012 CTSL1 enhances angiogenesis by increasing extracellular matrix degradation and remodelling. ILMN_2374036 CTSL1 up 0.00 0.43 1.13 11746740_a_at CTTN cortactin Plasma Membrane other up 0.04 0.85 0.84 ILMN_1744912 CTTN up 0.00 0.48 1.09 11722477_at CUL5 cullin 5 Nucleus ion channel down 0.00 -0.65 0.92 ILMN_2176955 CUL5 down 0.00 -0.33 0.52 11722479_a_at CUL5 cullin 5 Nucleus ion channel down 0.02 -0.60 1.16 11719366_s_at CXCL1 chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)Extracellular Space cytokine down 0.00 -0.97 1.06 ILMN_1787897 CXCL1 down 0.01 -0.49 0.81 11754114_a_at CXCL1 chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)Extracellular Space cytokine down 0.01 -0.72 1.14 11733296_s_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.01 -0.80 0.88 ILMN_1736190 CYP4F3 down 0.00 -0.57 0.97 11733297_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.00 -0.90 0.65 11749604_s_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.00 -0.77 1.07 11749605_x_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.00 -0.88 1.01 11749758_s_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.00 -0.77 0.88 11750945_x_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.01 -0.61 1.08 11759103_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.01 -0.70 0.98 11760318_at CYP4V2 cytochrome P450, family 4, subfamily V, polypeptide 2 Cytoplasm enzyme down 0.00 -0.50 1.10 ILMN_2054607 CYP4V2 down 0.00 -0.49 0.55 11720934_a_at DAGLB diacylglycerol lipase, beta Plasma Membrane enzyme up 0.00 0.61 1.17 ILMN_1658885 DAGLB up 0.04 0.33 1.05 11741500_a_at DAGLB diacylglycerol lipase, beta Plasma Membrane enzyme up 0.00 0.75 1.12 11719738_at DCP2 DCP2 decapping enzyme homolog (S. cerevisiae) Nucleus enzyme down 0.04 -0.48 1.15 ILMN_1669905 DCP2 down 0.05 -0.41 0.67 11720951_a_at DCUN1D4 DCN1, defective in cullin neddylation 1, domain containing 4 (S. cerevisiae)Nucleus other down 0.01 -0.77 0.47 ILMN_1801403 DCUN1D4 down 0.00 -0.56 0.22 11743972_a_at DDIT4 DNA-damage-inducible transcript 4 Cytoplasm other up 0.00 0.76 1.13 ILMN_1661599 DDIT4 up 0.00 0.79 1.14 18583960 DDX3X is a critical component of the TANK-binding kinase 1 (TBK1)-dependent innate immune response. 11750750_a_at DDX3X DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked Nucleus enzyme down 0.00 -0.70 1.16 ILMN_1794392 DDX3X down 0.00 -0.50 0.90 DDX3X 20127681 DDX3X is an antiviral MAVS (IPS-1) enhancer, where it can bind viral RNA to join it in the MAVS complex and this augments virus-mediated IFN-beta induction and host cell protection against virus infection. 11750751_x_at DDX3X DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked Nucleus enzyme down 0.00 -0.57 1.16 20657822 DDX3X RNA helicase can augment TBK1/IKKepsilon activity and hepatitis B virus (HBV) polymerase (HBV Pol) inhibits this TBK1/IKBKE activity by disrupting the interaction between IKBKE and DDX3X, providing an explanation for how HBV evades innate immune response in the early phase of the infection. 11743650_s_at DEK DEK oncogene Nucleus transcription regulator down 0.01 -0.58 1.14 ILMN_1747630 DEK down 0.00 -0.61 0.99 11743651_a_at DEK DEK oncogene Nucleus transcription regulator down 0.00 -0.66 1.15 11757280_s_at DEK DEK oncogene Nucleus transcription regulator down 0.02 -0.56 1.14 11723899_a_at DHRS9 dehydrogenase/reductase (SDR family) member 9 Cytoplasm enzyme updown 0.01 0.00 0.83 -0.87 0.24 0.72 ILMN_1733998 DHRS9 updown 0.00 0.00 0.79 -0.74 0.08 0.56 11754494_a_at DNHD1 dynein heavy chain domain 1 unknown other up 0.03 0.63 1.09 ILMN_1810267 DNHD1 up 0.00 0.41 1.16 11719154_a_at DRAM1 DNA-damage regulated autophagy modulator 1 Cytoplasm other down 0.01 -0.68 1.17 ILMN_1669376 DRAM1 down 0.00 -0.41 1.16 11717863_a_at DUSP5 dual specificity phosphatase 5 Nucleus phosphatase up 0.00 0.72 0.81 ILMN_1656501 DUSP5 up 0.00 0.45 0.08 11719373_at DYNLT3 dynein, light chain, Tctex-type 3 Cytoplasm other down 0.02 -0.67 1.14 ILMN_1681890 DYNLT3 down 0.02 -0.51 1.16 11739116_s_at EFR3A EFR3 homolog A (S. cerevisiae) Plasma Membrane other down 0.03 -0.45 1.14 ILMN_1664776 EFR3A down 0.00 -0.37 0.39 11722089_a_at EML3 echinoderm microtubule associated protein like 3 unknown other up 0.02 0.49 1.15 ILMN_1772644 EML3 up 0.00 0.72 0.22 11735192_a_at EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 Plasma Membrane G-protein coupled receptor down 0.02 -0.55 0.93 ILMN_2353633 EMR2 down 0.03 -0.46 0.65 11735193_x_at EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 Plasma Membrane G-protein coupled receptor down 0.03 -0.70 0.98 11745114_a_at EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 Plasma Membrane G-protein coupled receptor down 0.04 -0.50 0.86 11750377_a_at EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 Plasma Membrane G-protein coupled receptor down 0.01 -0.77 1.15 11752837_x_at EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 Plasma Membrane G-protein coupled receptor down 0.02 -0.67 1.12 11750862_a_at EMR3 egf-like module containing, mucin-like, hormone receptor-like 3 Plasma Membrane G-protein coupled receptor down 0.00 -0.98 1.17 ILMN_2348487 EMR3 down 0.01 -0.58 0.23 ILMN_1755873 EMR3 down 0.00 -0.49 0.52 11729574_at ENC1 ectodermal-neural cortex 1 (with BTB-like domain) Nucleus peptidase down 0.01 -0.42 0.64 ILMN_1779147 ENC1 down 0.03 -0.35 0.71 11727141_s_at EPB41L3 erythrocyte membrane protein band 4.1-like 3 Plasma Membrane other up 0.02 0.56 0.75 ILMN_2109197 EPB41L3 up 0.04 0.31 0.54 11727143_x_at EPB41L3 erythrocyte membrane protein band 4.1-like 3 Plasma Membrane other up 0.00 0.67 0.52 11745192_a_at EPB41L3 erythrocyte membrane protein band 4.1-like 3 Plasma Membrane other up 0.01 0.84 0.37 11722573_a_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase up 0.03 0.57 0.25 ILMN_1743145 ERAP2 up 0.00 0.42 0.42 Diabetes Page 78 of 111

11762512_a_at ERICH1 glutamate-rich 1 unknown other up 0.00 0.54 1.16 ILMN_1904238 ERICH1 up 0.00 0.59 1.16 ILMN_2104696 ERICH1 down 0.04 -0.32 1.21 11745025_a_at ERLIN2 ER lipid raft associated 2 Plasma Membrane other down 0.04 -0.57 0.65 ILMN_1700549 ERLIN2 down 0.00 -0.38 1.21 11726320_at ERO1L ERO1-like (S. cerevisiae) Cytoplasm enzyme down 0.03 -0.51 1.13 ILMN_1744963 ERO1L down 0.02 -0.44 1.22 11726321_a_at ERO1L ERO1-like (S. cerevisiae) Cytoplasm enzyme down 0.01 -0.66 1.07 11750454_a_at ETV7 ets variant 7 Nucleus transcription regulator up 0.00 1.93 0.06 ILMN_1700671 ETV7 up 0.01 0.27 0.36 11733841_a_at EVI2A ecotropic viral integration site 2A Plasma Membrane transmembrane receptor down 0.00 -0.99 1.09 ILMN_2369018 EVI2A down 0.00 -0.90 1.10 ILMN_1733579 EVI2A down 0.00 -0.69 1.22 11719662_s_at FAM188A family with sequence similarity 188, member A Nucleus other down 0.04 -0.52 0.92 ILMN_1725594 FAM188A down 0.00 -0.43 0.29 11739379_a_at FAM198B family with sequence similarity 198, member B Cytoplasm other down 0.02 -0.57 1.11 ILMN_1761941 FAM198B down 0.02 -0.59 0.78 11757534_s_at FAM198B family with sequence similarity 198, member B Cytoplasm other down 0.03 -0.67 1.12 11729673_s_at FAM200B family with sequence similarity 200, member B unknown other down 0.01 -0.75 1.16 ILMN_1675803 FAM200B down 0.00 -0.37 1.10 11742763_a_at FAM214A family with sequence similarity 214, member A unknown other down 0.00 -0.70 1.10 ILMN_1700733 FAM214A down 0.00 -0.53 0.42 11723025_at FAM26F family with sequence similarity 26, member F unknown other up 0.00 0.96 1.08 ILMN_2066849 FAM26F up 0.00 0.33 0.41 11723026_at FAM26F family with sequence similarity 26, member F unknown other up 0.00 0.69 1.11 11723685_a_at FAM46A family with sequence similarity 46, member A unknown other up 0.01 0.49 0.71 ILMN_1740466 FAM46A up 0.00 0.39 0.26 11723686_s_at FAM46A family with sequence similarity 46, member A unknown other up 0.01 0.48 0.89 11758890_at FAM46A family with sequence similarity 46, member A unknown other down 0.02 -0.72 1.01 11758153_x_at FAM83H family with sequence similarity 83, member H unknown other up 0.02 0.59 1.02 ILMN_1751328 FAM83H up 0.00 0.45 1.03 11734734_s_at FAR1 fatty acyl CoA reductase 1 Cytoplasm enzyme down 0.00 -0.66 1.11 ILMN_2143250 FAR1 down 0.00 -0.60 1.18 11734735_a_at FAR1 fatty acyl CoA reductase 1 Cytoplasm enzyme down 0.00 -0.73 1.11 11734736_a_at FAR1 fatty acyl CoA reductase 1 Cytoplasm enzyme down 0.00 -0.90 1.10 11734737_a_at FAR1 fatty acyl CoA reductase 1 Cytoplasm enzyme down 0.00 -0.80 1.14 11750639_s_at FBXO11 F-box protein 11 Cytoplasm enzyme down 0.01 -0.48 1.16 ILMN_1713682 FBXO11 down 0.00 -0.46 0.69 11742889_at FBXO6 F-box protein 6 Cytoplasm enzyme up 0.00 0.81 0.07 ILMN_1701455 FBXO6 up 0.00 0.53 0.10 11716486_at FCGBP Fc fragment of IgG binding protein Extracellular Space other up 0.00 0.73 0.84 ILMN_2302757 FCGBP up 0.00 0.48 0.09 11724171_a_at FCHO2 FCH domain only 2 Cytoplasm other down 0.00 -0.97 1.13 ILMN_1670322 FCHO2 down 0.00 -0.63 1.19 11724172_s_at FCHO2 FCH domain only 2 Cytoplasm other down 0.00 -0.94 1.12 11752619_a_at FCRL2 Fc receptor-like 2 unknown other down 0.04 -0.69 0.65 ILMN_1791329 FCRL2 down 0.03 -0.57 0.14 11727533_a_at FEZ2 fasciculation and elongation protein zeta 2 (zygin II) Cytoplasm other down 0.04 -0.41 1.01 ILMN_1739586 FEZ2 down 0.00 -0.41 1.22 11736116_a_at FGFR1OP2 FGFR1 oncogene partner 2 Cytoplasm other down 0.00 -0.87 1.12 ILMN_1657436 FGFR1OP2 down 0.02 -0.26 0.41 11763278_s_at FGFR1OP2 FGFR1 oncogene partner 2 Cytoplasm other down 0.00 -0.95 1.04 11733701_a_at FKBP11 FK506 binding protein 11, 19 kDa Cytoplasm enzyme up 0.03 0.49 0.30 ILMN_1787345 FKBP11 up 0.01 0.33 0.16 11731054_s_at FNIP1 folliculin interacting protein 1 Cytoplasm other down 0.00 -0.74 1.07 ILMN_1737343 FNIP1 down 0.01 -0.66 0.27 11744140_a_at FOLR3 folate receptor 3 (gamma) Extracellular Space other down 0.00 -1.12 0.46 ILMN_1730454 FOLR3 down 0.00 -0.60 0.84 11744141_x_at FOLR3 folate receptor 3 (gamma) Extracellular Space other down 0.00 -1.28 0.37 11723169_s_at FOXN2 forkhead box N2 Nucleus transcription regulator down 0.01 -0.45 1.10 ILMN_1736510 FOXN2 down 0.00 -0.42 1.22 11734034_a_at FPR2 formyl peptide receptor 2 Plasma Membrane G-protein coupled receptor down 0.00 -0.93 1.17 ILMN_2392569 FPR2 down 0.05 -0.39 1.21 11739140_a_at FPR2 formyl peptide receptor 2 Plasma Membrane G-protein coupled receptor down 0.01 -0.71 1.16 11745309_a_at FRMD3 FERM domain containing 3 unknown other up 0.02 0.94 0.97 ILMN_1698725 FRMD3 up 0.00 0.79 0.40 11750746_a_at FRMD3 FERM domain containing 3 unknown other up 0.00 0.95 1.03 11736092_at GCA grancalcin, EF-hand calcium binding protein Cytoplasm other down 0.00 -0.93 1.14 ILMN_1800602 GCA down 0.02 -0.61 0.86 11721733_a_at GCH1 GTP cyclohydrolase 1 Cytoplasm enzyme up 0.04 0.52 1.00 ILMN_1812759 GCH1 up 0.01 0.34 1.06 ILMN_1788802 GCH1 down 0.04 -0.48 1.21 11721010_a_at GDPD5 glycerophosphodiester phosphodiesterase domain containing 5 unknown other up 0.00 0.75 1.17 ILMN_1701643 GDPD5 up 0.00 0.51 1.13 11722945_a_at GLT1D1 glycosyltransferase 1 domain containing 1 Extracellular Space enzyme down 0.01 -0.83 1.16 ILMN_1656327 GLT1D1 down 0.00 -0.62 0.75 11749165_a_at GLT1D1 glycosyltransferase 1 domain containing 1 Extracellular Space enzyme down 0.02 -0.89 1.03 11737747_a_at GMFB glia maturation factor, beta Cytoplasm growth factor down 0.03 -0.67 1.17 ILMN_2093674 GMFB down 0.00 -0.55 0.95 11737748_a_at GMFB glia maturation factor, beta Cytoplasm growth factor down 0.01 -1.00 0.53 11755222_a_at GNA13 guanine nucleotide binding protein (G protein), alpha 13 Plasma Membrane enzyme down 0.00 -0.63 1.10 ILMN_1758906 GNA13 down 0.03 -0.37 1.21 GNAI3 21209316 GNAI3 is a G protein involved in autophagy signalling pathways and is tightly regulated through its interaction with its GEF activator (CCDC88A) and GDI inhibitor (GPSM1). During starving conditions, GPSM1 binds to GNAI3 in MAP1LC3A-positive membranes to promote autophagy. When stimulated by growth factors, CCDC88A promotes the dissociation of GPSM1::GNAI3 complex to initiate anti-autophagy signalling pathways. 11727776_at GNAI3 guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptideCytoplasm 3 enzyme down 0.03 -0.58 1.06 ILMN_1696003 GNAI3 down 0.00 -0.43 1.13 11718843_s_at GNG10 guanine nucleotide binding protein (G protein), gamma 10 Plasma Membrane enzyme down 0.04 -0.68 1.08 ILMN_1757074 GNG10 down 0.00 -0.61 1.22 11756632_a_at GNLY granulysin Cytoplasm other up 0.04 0.52 0.15 ILMN_1708779 GNLY up 0.02 0.67 0.08 11763755_a_at GNLY granulysin Cytoplasm other up 0.01 0.48 0.40 11763756_x_at GNLY granulysin Cytoplasm other up 0.03 0.45 0.23 11721866_a_at GNPDA2 glucosamine-6-phosphate deaminase 2 unknown enzyme down 0.02 -0.79 0.51 ILMN_1691567 GNPDA2 down 0.04 -0.47 0.31 11755957_s_at GNRHR2 gonadotropin-releasing hormone (type 2) receptor 2 Plasma Membrane G-protein coupled receptor down 0.04 -0.44 1.04 ILMN_2224619 GNRHR2 down 0.00 -0.52 0.91 11737507_a_at GPBAR1 G protein-coupled bile acid receptor 1 Plasma Membrane G-protein coupled receptor up 0.01 0.72 1.14 ILMN_1727709 GPBAR1 up 0.01 0.44 0.45 ILMN_2316386 GPBAR1 updown 0.00 0.01 0.68 -0.43 0.55 0.41 11718503_a_at GPCPD1 glycerophosphocholine phosphodiesterase GDE1 homolog (S. cerevisiae) unknown other down 0.04 -0.55 1.17 ILMN_1701111 GPCPD1 down 0.01 -0.44 0.71 11716395_a_at GPR56 G protein-coupled receptor 56 Plasma Membrane G-protein coupled receptor up 0.02 0.88 0.34 ILMN_2352097 GPR56 up 0.00 0.68 0.11 ILMN_2384122 GPR56 up 0.00 0.78 0.08 11731669_at GPR65 G protein-coupled receptor 65 Plasma Membrane G-protein coupled receptor down 0.02 -0.77 1.16 ILMN_1734740 GPR65 down 0.02 -0.51 0.50 11716377_s_at GRN granulin Extracellular Space growth factor down 0.01 -0.65 1.15 ILMN_1811702 GRN down 0.02 -0.38 1.05 GRN 21497117 GRN is an essential secreted cofactor that potentiates TLR9-driven response to CpG olignonucletides by binding directly to CpG oligos and TLR9. GRN deficient murine macrophages showed impaired delivery of CpG oligos to endolysosomal compartments and reduced response to CpG. (Demonstrated in murine model) 11745725_a_at GRN granulin Extracellular Space growth factor down 0.01 -0.73 1.17 11745726_x_at GRN granulin Extracellular Space growth factor down 0.01 -0.70 1.17 11734159_a_at HACE1 HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 Cytoplasm enzyme down 0.01 -0.69 0.90 ILMN_1740217 HACE1 down 0.01 -0.37 1.20 11751231_a_at HAL histidine ammonia-lyase Cytoplasm enzyme down 0.03 -0.56 0.20 ILMN_2074748 HAL down 0.03 -0.53 0.94 11752202_a_at HAL histidine ammonia-lyase Cytoplasm enzyme down 0.01 -0.64 0.28 11724781_a_at HERC4 HECT and RLD domain containing E3 ubiquitin protein ligase 4 Cytoplasm enzyme down 0.00 -0.60 1.09 ILMN_1678922 HERC4 down 0.00 -0.51 0.71 11724782_x_at HERC4 HECT and RLD domain containing E3 ubiquitin protein ligase 4 Cytoplasm enzyme down 0.01 -0.48 1.17 11751957_a_at HERC4 HECT and RLD domain containing E3 ubiquitin protein ligase 4 Cytoplasm enzyme down 0.00 -0.68 1.15 11758560_s_at HERC4 HECT and RLD domain containing E3 ubiquitin protein ligase 4 Cytoplasm enzyme down 0.03 -0.48 1.14 11724021_at HIST1H2BD histone cluster 1, H2bd Nucleus other down 0.01 -0.63 1.16 ILMN_1651496 HIST1H2BD down 0.00 -0.59 1.08 11728152_a_at HIST1H2BD histone cluster 1, H2bd Nucleus other down 0.01 -0.71 1.04 ILMN_1758623 HIST1H2BD down 0.00 -0.55 0.85 11728153_x_at HIST1H2BD histone cluster 1, H2bd Nucleus other down 0.04 -0.65 1.15 19890330 HMGB1 functions as universal sentinel for nucleic-acid-mediated innate immune responses. 11728049_s_at HIST1H4A (includes others)histone cluster 1, H4a Nucleus other down 0.02 -0.89 0.76 ILMN_2075334 HIST1H4A (includes others)up 0.01 0.51 0.14 19914413 HMGB1 activates innate immunity mechanisms as a complex with DNA, lipids and/or pro-inflammatory cytokines. ILMN_1853899 HIST1H4A (includes others)down 0.05 -0.41 1.14 20419158 HMGB1 is an alarmin and a key mediator of natural killer (NK)-dendritic cell (DC) cross-talk and plays a pivotal role in the escape of Human Immunodeficiency Virus (HIV)-infected dendritic cells from TRAIL-mediated NK cell cytotoxicity during NK-DC cross-talk by upregulating c-FLIP and c-IAP2 expression. 11739025_a_at HMGB1 high mobility group box 1 Nucleus transcription regulator down 0.04 -0.61 1.12 ILMN_1791466 HMGB1 updown 0.00 0.03 0.62 -0.54 0.40 0.89 HMGB1 21372296 HMGB1 is an endogenous TLR4 ligand in macrophages and its release in wounds initiates TLR4-dependent responses that contribute to neovascularization. (Demonstrated in murine model) 11739026_x_at HMGB1 high mobility group box 1 Nucleus transcription regulator down 0.00 -0.66 1.14 21389264 HMGB1 is found in high concentrations within neutrophil extracellular traps (NETs). HMGB1 is a neutrophil protein that facilitates the uptake and recognition of mammalian DNA by plasmacytoid dendritic cells, and may play a role in Systemic Lupus Erthermatosus autoimmunity. 11729119_a_at HSPA1A/HSPA1B heat shock 70kDa protein 1A Cytoplasm other down 0.04 -0.70 0.53 ILMN_1789074 HSPA1A/HSPA1B down 0.00 -0.89 0.62 21860212 HMGB1 plays a key regulatory role in polymorphonuclear neutrophil (PMN) recruitment to inflammatory tissues. Low concentrations of HMGB1 (50-100 ng/ml) reduce baseline PMN migration as well as formyl-methionyl-leucyl-phenylalanine- and IL8-induced PMN chemotaxis, whereas higher HMGB1 concentrations (5000 ng/ml) have a chemoattractant effect on PMN through IL8 production. 11729120_x_at HSPA1A/HSPA1B heat shock 70kDa protein 1A Cytoplasm other down 0.02 -0.73 0.98 ILMN_1660436 HSPA1A/HSPA1B down 0.01 -0.52 0.32 21871094 HMGB1 has a pathogenic role in arthritis, where in complex with lipopolysaccharide, IL1A or IL1B, HMGB1 boosts the production of proinflammatory cytokines and MMP3 as demonstrated in synovial fibroblasts from rheumatoid arthritis and osteoarthritis patients. 11744413_x_at HSPA1A/HSPA1B heat shock 70kDa protein 1A Cytoplasm other down 0.01 -0.75 1.15 11723050_a_at HSPA6 heat shock 70kDa protein 6 (HSP70B) unknown other down 0.01 -0.75 1.16 ILMN_1806165 HSPA6 down 0.00 -0.83 0.40 11748629_a_at IFRD1 interferon-related developmental regulator 1 Nucleus other down 0.00 -0.69 1.17 ILMN_1667561 IFRD1 down 0.00 -0.45 0.76 11716129_at IGF2R insulin-like growth factor 2 receptor Plasma Membrane transmembrane receptor down 0.05 -0.79 1.11 ILMN_1807662 IGF2R down 0.00 -0.54 0.40 11763122_x_at IGLL1/IGLL5 immunoglobulin lambda-like polypeptide 1 Plasma Membrane other up 0.03 0.80 0.18 ILMN_2393765 IGLL1/IGLL5 up 0.00 0.74 0.38 11728427_at IKBIP IKBKB interacting protein Cytoplasm other down 0.02 -0.76 1.17 ILMN_1701402 IKBIP down 0.02 -0.39 1.19 20026737 IL15 is a pluripotent anti-apoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. IL15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. 11758567_s_at IKBIP IKBKB interacting protein Cytoplasm other down 0.00 -0.79 1.13 22084435 IL15 regulates homeostasis and terminal maturation of NKT cells. (Demonstrated in mice) 11725255_a_at IL15 interleukin 15 Extracellular Space cytokine up 0.04 0.64 0.50 ILMN_1724181 IL15 up 0.00 0.51 0.16 IL15 22940097 IL15 secreted by inflammatory monocytes is critical for the differentiation of memory CD8(+) T and NK lymphocytes into antimicrobial effector cells. (Demonstrated in mice) 11740881_x_at IL15 interleukin 15 Extracellular Space cytokine up 0.04 0.79 0.68 11718841_s_at IL8 interleukin 8 Extracellular Space cytokine down 0.00 -1.19 1.16 ILMN_2184373 IL8 down 0.00 -1.03 0.68 IL8 17220369 IL8 is produced by airway epithelial cells in response to invading bacteria and mediates airway epithelial defence against bacterial infection via the DUOX1-TACE-TGF-alpha-EGFR signalling pathway. 11754026_a_at IL8 interleukin 8 Extracellular Space cytokine down 0.02 -0.66 1.14 11719141_a_at INSIG2 insulin induced gene 2 Cytoplasm other down 0.00 -0.56 1.17 ILMN_1676629 INSIG2 down 0.00 -0.46 1.22 11719142_a_at INSIG2 insulin induced gene 2 Cytoplasm other down 0.00 -0.61 1.09 11719143_x_at INSIG2 insulin induced gene 2 Cytoplasm other down 0.00 -0.55 1.16 11731746_at IPMK inositol polyphosphate multikinase Nucleus kinase down 0.02 -0.77 1.13 ILMN_1724346 IPMK down 0.03 -0.42 0.41 11718012_at IRS2 insulin receptor substrate 2 Cytoplasm enzyme down 0.00 -0.65 1.01 ILMN_2083469 IRS2 down 0.00 -0.68 1.13 11756806_a_at ISG20 interferon stimulated exonuclease gene 20kDa Nucleus enzyme up 0.00 0.68 0.46 ILMN_1659913 ISG20 up 0.00 0.67 0.39 ISG20 15064795 ISG20 is an IFN-induced 3'-5' exonuclease that is strongly induced by viral double stranded RNA and is activated by RELA/NFKB1. 11719292_a_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other down 0.00 -0.56 0.63 ILMN_1690099 ITGB1BP1 up 0.03 0.34 1.03 11719293_s_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other down 0.00 -0.64 0.88 11754810_a_at ITGB5 integrin, beta 5 Plasma Membrane other EMD121974 up 0.00 0.66 1.17 ILMN_1668374 ITGB5 updown 0.00 0.01 0.60 -0.55 1.03 0.08 11718828_s_at ITM2C integral membrane protein 2C Cytoplasm other up 0.01 0.53 0.53 ILMN_2366041 ITM2C up 0.00 0.51 0.22 11753667_s_at ITM2C integral membrane protein 2C Cytoplasm other up 0.03 0.55 0.63 11763275_x_at ITSN2 intersectin 2 Cytoplasm other down 0.01 -0.58 1.16 ILMN_1714372 ITSN2 down 0.02 -0.52 0.78 11718637_s_at JMJD1C jumonji domain containing 1C Nucleus other down 0.00 -0.76 1.17 ILMN_1764970 JMJD1C down 0.00 -0.64 0.84 11746223_a_at JMJD1C jumonji domain containing 1C Nucleus other down 0.00 -0.73 1.16 ILMN_2410742 JMJD1C down 0.02 -0.41 1.21 11751878_a_at JMJD1C jumonji domain containing 1C Nucleus other down 0.00 -0.67 1.16 11732454_at KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 Plasma Membrane ion channel down 0.00 -1.08 1.11 ILMN_1675756 KCNJ15 down 0.00 -0.58 1.21 11732455_at KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 Plasma Membrane ion channel down 0.00 -0.84 1.14 11722626_at KIAA1033 KIAA1033 Cytoplasm other down 0.00 -0.70 1.05 ILMN_1782222 KIAA1033 down 0.00 -0.50 0.53 11722627_at KIAA1033 KIAA1033 Cytoplasm other down 0.00 -0.77 0.99 11720780_a_at KIAA1324 KIAA1324 Plasma Membrane other down 0.00 -0.98 0.37 ILMN_1771482 KIAA1324 down 0.01 -0.51 0.06 11760258_x_at KIAA1324 KIAA1324 Plasma Membrane other down 0.00 -0.76 0.29 11722881_at KIAA1468 KIAA1468 unknown other down 0.00 -0.71 1.01 ILMN_1798346 KIAA1468 down 0.02 -0.39 1.20 11758265_s_at KIAA1468 KIAA1468 unknown other down 0.00 -0.67 1.10 11743553_a_at KIN KIN, antigenic determinant of recA protein homolog (mouse) Nucleus other down 0.01 -0.61 1.10 ILMN_1670298 KIN down 0.03 -0.32 1.12 11743554_x_at KIN KIN, antigenic determinant of recA protein homolog (mouse) Nucleus other down 0.01 -0.59 1.16 11724676_a_at KLHL2 kelch-like 2, Mayven (Drosophila) Cytoplasm transporter down 0.01 -0.69 1.14 ILMN_1701837 KLHL2 down 0.02 -0.47 1.12 11740668_a_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor up 0.00 1.01 0.98 ILMN_2055781 KLRF1 up 0.01 0.65 0.13 11740669_x_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor up 0.01 1.02 0.75 11745699_a_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor up 0.00 0.99 1.01 11753219_a_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor up 0.01 0.94 1.06 11740592_a_at KRT72 keratin 72 unknown other up 0.00 0.68 1.07 ILMN_1695812 KRT72 up 0.00 0.68 0.47 11726965_a_at L3MBTL3 l(3)mbt-like 3 (Drosophila) Nucleus other down 0.01 -0.49 1.17 ILMN_1727495 L3MBTL3 down 0.01 -0.43 1.01 11733718_x_at LAIR2 leukocyte-associated immunoglobulin-like receptor 2 Plasma Membrane other up 0.01 0.72 0.49 ILMN_1807491 LAIR2 up 0.05 0.28 0.30 11740754_a_at LAIR2 leukocyte-associated immunoglobulin-like receptor 2 Plasma Membrane other up 0.00 0.67 0.36 ILMN_2323933 LAIR2 up 0.00 0.34 0.08 11753776_x_at LAIR2 leukocyte-associated immunoglobulin-like receptor 2 Plasma Membrane other up 0.00 0.80 0.34 11742685_a_at LAMP2 lysosomal-associated membrane protein 2 Plasma Membrane enzyme down 0.01 -0.65 1.17 ILMN_1917290 LAMP2 down 0.01 -0.33 1.21 11749876_a_at LAMP2 lysosomal-associated membrane protein 2 Plasma Membrane enzyme down 0.01 -0.94 1.15 ILMN_2279961 LAMP2 down 0.00 -0.63 1.12 ILMN_1673282 LAMP2 down 0.00 -0.68 1.03 ILMN_1659753 LAMP2 down 0.01 -0.42 1.22 ILMN_2243687 LAMP2 down 0.00 -0.50 1.21 11718768_a_at LAMTOR3 late endosomal/lysosomal adaptor, MAPK and MTOR activator 3 Cytoplasm other down 0.00 -0.79 1.16 ILMN_1659415 LAMTOR3 down 0.00 -0.48 1.19 11718769_a_at LAMTOR3 late endosomal/lysosomal adaptor, MAPK and MTOR activator 3 Cytoplasm other down 0.02 -0.79 1.03 11721243_a_at LAP3 leucine aminopeptidase 3 Cytoplasm peptidase up 0.00 1.37 0.20 ILMN_1683792 LAP3 up 0.00 0.68 0.24 11754408_s_at LDB2 LIM domain binding 2 Nucleus transcription regulator down 0.02 -0.56 0.32 ILMN_1800697 LDB2 down 0.01 -0.36 1.22 11746636_a_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.04 0.61 1.12 ILMN_1904481 LEF1 up 0.01 0.57 1.04 11747931_a_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.03 0.64 1.06 ILMN_2213136 LEF1 down 0.00 -0.64 0.26 11721228_s_at LEMD3 LEM domain containing 3 Nucleus other down 0.00 -0.57 1.12 ILMN_1727361 LEMD3 down 0.00 -0.52 0.51 11731798_a_at LGALS2 lectin, galactoside-binding, soluble, 2 Cytoplasm other updown 0.03 0.01 0.65 -0.44 0.15 0.09 ILMN_1687306 LGALS2 down 0.05 -0.42 0.11 LGALS2 15356130 LGASL2 binds to T cells in a beta-galactoside-specific manner and acts as pro-apoptotic effector for activated T cells. 11715370_s_at LGALS3BP lectin, galactoside-binding, soluble, 3 binding protein Plasma Membrane transmembrane receptor up 0.00 0.82 1.15 ILMN_1659688 LGALS3BP up 0.01 0.37 1.18 11736462_a_at LILRA2 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 2 Membrane other down 0.01 -0.73 1.17 ILMN_1716983 LILRA2 down 0.00 -0.59 0.93 LILRA2 22479404 LILRA2-activation of monocytes is distinct from LPS activation, as assessed by the secreted cytokine profile. LILRA2 cross-linking also results in inhibition of FCGR1A-dependent phagocytosis in monocytes. 11736463_x_at LILRA2 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 2 Membrane other down 0.01 -0.66 1.17 11749617_a_at LILRA2 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 2 Membrane other down 0.00 -0.68 1.16 11749618_x_at LILRA2 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 2 Membrane other down 0.00 -0.69 1.17 11752892_x_at LILRA2 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 2 Membrane other down 0.03 -0.61 1.17 11730656_a_at LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain),Extracellular member 3 Space other down 0.00 -0.83 0.57 ILMN_1661631 LILRA3 down 0.00 -0.77 1.16 11732265_at LILRB1 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains),Plasma Membranemember 1 transmembrane receptor up 0.01 0.72 0.62 ILMN_2316974 LILRB1 up 0.00 0.46 0.34 11732266_x_at LILRB1 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains),Plasma Membranemember 1 transmembrane receptor up 0.01 0.66 0.68 11752420_x_at LOC100507607 (includes others)nuclear pore complex interacting protein-like 2 unknown other up 0.03 0.64 0.17 ILMN_2147105 LOC100507607 (includes others)up 0.02 0.39 0.24 11731076_a_at LONRF1 LON peptidase N-terminal domain and ring finger 1 unknown other down 0.02 -0.60 1.03 ILMN_1705953 LONRF1 down 0.00 -0.35 1.01 11731077_a_at LONRF1 LON peptidase N-terminal domain and ring finger 1 unknown other down 0.03 -0.58 1.12 11757558_s_at LONRF1 LON peptidase N-terminal domain and ring finger 1 unknown other down 0.03 -0.59 1.17 11729750_a_at LPAR1 lysophosphatidic acid receptor 1 Plasma Membrane G-protein coupled receptor down 0.00 -0.76 0.76 ILMN_1701441 LPAR1 down 0.04 -0.38 0.48 11743071_a_at LPAR6 lysophosphatidic acid receptor 6 Plasma Membrane G-protein coupled receptor down 0.03 -0.88 0.96 ILMN_1786429 LPAR6 updown 0.00 0.00 0.61 -0.73 0.95 1.02 11740275_a_at LRRC25 leucine rich repeat containing 25 unknown other down 0.03 -0.69 1.14 ILMN_1766487 LRRC25 down 0.04 -0.42 1.00 11756933_x_at LRRC25 leucine rich repeat containing 25 unknown other down 0.04 -0.60 1.13 11734144_s_at LRRC37A3 (includes others)leucine rich repeat containing 37, member A3 unknown other up 0.02 0.40 0.42 ILMN_1783673 LRRC37A3 (includes others)up 0.05 0.36 0.68 11716311_x_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other up 0.01 1.16 0.89 ILMN_1719032 LSM3 up 0.04 0.36 0.75 11753808_s_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other up 0.01 1.18 0.76 11753809_x_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other up 0.00 1.13 0.86 11757092_s_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other up 0.00 1.11 0.90 11739090_at LUC7L3 LUC7-like 3 (S. cerevisiae) Nucleus other down 0.00 -0.76 1.02 ILMN_1728180 LUC7L3 down 0.02 -0.40 1.11 11749811_a_at LUC7L3 LUC7-like 3 (S. cerevisiae) Nucleus other down 0.00 -1.08 1.10 ILMN_2299072 LUC7L3 down 0.04 -0.58 0.53 11723474_a_at LYPLAL1 lysophospholipase-like 1 Cytoplasm enzyme down 0.01 -0.74 0.99 ILMN_2142117 LYPLAL1 down 0.04 -0.35 0.96 11724410_x_at MARCH2 membrane-associated ring finger (C3HC4) 2, E3 ubiquitin protein ligase Cytoplasm enzyme up 0.04 0.51 1.17 ILMN_1669592 MARCH2 up 0.02 0.33 1.05 ILMN_1703142 MARCH2 down 0.05 -0.28 0.85 11719890_a_at MARCH7 membrane-associated ring finger (C3HC4) 7, E3 ubiquitin protein ligase Extracellular Space other down 0.01 -0.57 1.15 ILMN_1717337 MARCH7 down 0.00 -0.55 0.42 11746613_a_at MARCH7 membrane-associated ring finger (C3HC4) 7, E3 ubiquitin protein ligase Extracellular Space other down 0.01 -0.59 1.06 20472936 ABCA1 promotes the efflux of bacterial lipopolysaccharide (LPS) from macrophages and accelerates recovery from LPS-induced tolerance. 11721629_a_at MAFB v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) Nucleus other up 0.00 0.78 1.15 ILMN_1764709 MAFB up 0.00 0.66 0.12 MAFB 20581830 MAFB binds to IRF3, impairing the recruitment of co-activators to IRF3 and antagonizing antiviral responses. 11721630_at MAFB v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) Nucleus other up 0.01 0.97 0.29 11757798_s_at MAFB v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) Nucleus other up 0.00 1.14 0.38 11746248_x_at MANSC1 MANSC domain containing 1 unknown other down 0.00 -1.12 1.17 ILMN_2142752 MANSC1 down 0.00 -0.86 0.24 11754973_x_at MANSC1 MANSC domain containing 1 unknown other down 0.00 -0.87 1.16 11723771_a_at MASTL microtubule associated serine/threonine kinase-like Cytoplasm kinase down 0.00 -0.64 1.04 ILMN_1682336 MASTL down 0.00 -0.44 1.22 11741648_s_at MBNL1 muscleblind-like splicing regulator 1 Nucleus other down 0.02 -0.52 1.17 ILMN_2313158 MBNL1 up 0.01 0.23 0.58 11743661_a_at MBNL1 muscleblind-like splicing regulator 1 Nucleus other down 0.00 -0.76 1.13 ILMN_1807304 MBNL1 down 0.01 -0.33 1.13 11734952_a_at MBNL3 muscleblind-like splicing regulator 3 Nucleus other up 0.05 0.82 1.17 ILMN_2303166 MBNL3 up 0.00 0.55 0.82 11763736_a_at MBNL3 muscleblind-like splicing regulator 3 Nucleus other up 0.04 0.84 1.17 11763737_x_at MBNL3 muscleblind-like splicing regulator 3 Nucleus other up 0.04 0.76 1.17 11737839_a_at MBOAT7 membrane bound O-acyltransferase domain containing 7 Plasma Membrane other down 0.03 -0.65 1.10 ILMN_1722218 MBOAT7 down 0.05 -0.59 0.42 11732568_at MBP myelin basic protein Extracellular Space other down 0.05 -0.45 0.54 ILMN_2398939 MBP down 0.00 -0.66 0.29 11757273_s_at MBP myelin basic protein Extracellular Space other down 0.02 -0.66 0.93 ILMN_2331544 MBP down 0.02 -0.53 0.25 11725166_s_at MED23 mediator complex subunit 23 Nucleus transcription regulator down 0.04 -0.43 1.13 ILMN_1690999 MED23 down 0.02 -0.49 0.49 11720022_a_at MME membrane metallo-endopeptidase Plasma Membrane peptidase down 0.01 -0.81 0.82 ILMN_1678170 MME down 0.01 -0.65 0.08 11741562_a_at MME membrane metallo-endopeptidase Plasma Membrane peptidase down 0.02 -0.69 1.00 11719226_at MOB1B MOB kinase activator 1B Cytoplasm other down 0.00 -0.64 0.62 ILMN_1793349 MOB1B down 0.00 -0.40 0.75 11719073_a_at MOB4 MOB family member 4, phocein Cytoplasm other down 0.04 -0.81 1.15 ILMN_1733356 MOB4 down 0.00 -0.48 0.19 11739834_s_at MOB4 MOB family member 4, phocein Cytoplasm other down 0.01 -0.71 1.16 11732209_a_at MON2 MON2 homolog (S. cerevisiae) Cytoplasm other down 0.02 -0.59 0.91 ILMN_1697200 MON2 down 0.02 -0.39 0.80 11759511_at MOSPD2 motile sperm domain containing 2 unknown other down 0.02 -0.56 1.12 ILMN_1766094 MOSPD2 down 0.02 -0.34 0.88 11764146_s_at MOSPD2 motile sperm domain containing 2 unknown other down 0.00 -0.61 1.08 11718659_x_at MOV10 Mov10, Moloney leukemia virus 10, homolog (mouse) Nucleus enzyme up 0.00 0.59 0.77 ILMN_1725700 MOV10 up 0.00 0.54 0.26 MOV10 23093941 MOV10 associates with LINE1 ribonucleoprotein particles and restricts endogenous retrovirus transposition. 11749660_a_at MOV10 Mov10, Moloney leukemia virus 10, homolog (mouse) Nucleus enzyme up 0.00 0.66 0.57 11976320 MYD88 is a Toll/IL-1R homology (TIR) domain containing adaptor which recruits IRAK1 possibly through IRAK4. 11754705_a_at MRPL43 mitochondrial ribosomal protein L43 Cytoplasm translation regulator down 0.00 -0.51 0.13 ILMN_1652147 MRPL43 updown 0.00 0.02 0.53 -0.39 0.70 0.08 18327267 MYD88 can interact with bacterial TIR domain containing-proteins (Tcps) identified in Escherichia coli CFT073 (TcpC) and Brucella melitensis (TcpB) and interfere with MYD88-dependent pathway, thus suppressing innate immunity and increasing virulence. 11753900_x_at MT2A metallothionein 2A Cytoplasm other up 0.00 0.76 0.37 ILMN_1686664 MT2A up 0.00 1.00 0.08 16354686 MYD88 binding with interleukin-1 (IL-1) receptor (IL1R1) is required for inducing endocytosis of IL1R1 following ligand binding. 11758729_x_at MT2A metallothionein 2A Cytoplasm other up 0.00 0.60 0.82 9734363 MYD88 is a key adaptor/regulator molecule for the Toll/IL-1R family of receptors for innate immunity. 11730235_a_at MYADM myeloid-associated differentiation marker Nucleus other down 0.01 -0.69 1.17 ILMN_2308849 MYADM down 0.00 -0.63 0.30 9430229 MYD88 interacts with the IL-1 receptor and blocks NF-kappaB activation induced by IL-1, but not by TNF. 11747538_a_at MYD88 myeloid differentiation primary response gene (88) Plasma Membrane other down 0.02 -0.62 1.12 ILMN_1738523 MYD88 down 0.00 -0.51 1.09 MYD88 20167866 TLR-2/MyD88/PI3K/Rac1/Akt pathway mediates LTA-induced MAPKs activation, which in turn initiates the activation of NF-kappaB, and ultimately induces cPLA2/COX-2-dependent PGE2 and IL-6 generation. 11729192_a_at MYNN myoneurin Nucleus transcription regulator down 0.00 -1.00 1.02 ILMN_1672287 MYNN down 0.02 -0.45 1.01 20519121 MYD88 plays a critical role in reverse cholesterol transport in vitro and in vivo, in part through promoting ATP-binding cassette A1 transporter upregulation, coupling cholesterol trafficking to inflammation through MYD88 and identifying innate immunity as a physiologic signal in cholesterol homeostasis. 11729193_s_at MYNN myoneurin Nucleus transcription regulator down 0.02 -0.76 1.10 21057262 MYD88 and IRAK1 autosomal recessive deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity and predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation. 11719186_a_at N4BP2L2 NEDD4 binding protein 2-like 2 Nucleus other down 0.01 -0.68 0.24 ILMN_1797893 N4BP2L2 down 0.00 -0.41 0.48 21248248 MYD88 is essential in restricting TLR3 signalling and the host protection from unwanted immunopathologies associated with excessive production of IFNB1. MYD88 inhibits TLR3 signalling by impairing IKBKE-mediated induction of IRF3, and consequently the expression IFNB1 and CCL5. 11739475_s_at NAB1 NGFI-A binding protein 1 (EGR1 binding protein 1) Nucleus transcription regulator down 0.00 -0.68 1.17 ILMN_1774617 NAB1 down 0.00 -0.57 1.21 21283748 MYD88 is activated by MHC class II in response to staphylococcal enterotoxins and is crucial for the induction of pro-inflammatory cytokines. 11743110_at NAMPT nicotinamide phosphoribosyltransferase Extracellular Space cytokine down 0.01 -0.80 1.15 ILMN_1653871 NAMPT down 0.00 -0.65 1.09 NAMPT 21325272 MYD88 is a key signalling adapter in TLR signalling. MYD88 aggregates in the cell as distinct foci and co-localizes with IRAK4 in these Myddosomes - the formation of which is required for MYD88 function. 11743111_s_at NAMPT nicotinamide phosphoribosyltransferase Extracellular Space cytokine down 0.02 -0.72 1.17 ILMN_1753111 NAMPT down 0.01 -0.76 0.23 21353603 MYD88 is required in dendritic cells stimulated with TLR9 ligand for the enhancement of T cell-dependent antibody response. In addition, MYD88 is required in B cells to facilitate strong anti-viral antibody responses. (Demonstrated in murine model) 11732206_a_at NAP1L1 nucleosome assembly protein 1-like 1 Nucleus other down 0.03 -0.61 0.34 ILMN_1699208 NAP1L1 down 0.00 -0.43 1.02 21422180 MYD88 deficient macrophages displayed impaired interaction with fungal yeast cells and produced low levels of pro-inflammatory cytokines. MYD88 signalling is important in the activation of fungicidal mechanisms and the induction of protective innate immune responses against P. brasiliensis. (Demonstrated in murine model) 11730771_at NAPG N-ethylmaleimide-sensitive factor attachment protein, gamma Cytoplasm transporter down 0.00 -0.67 1.07 ILMN_1788268 NAPG down 0.03 -0.49 0.43 22028692 MYD88 mediates cytoskeletal remodelling and late spreading of lipopolysaccharide (LPS)-stimulated macrophages. (Demonstrated in mice) 11718026_a_at NCOA7 nuclear receptor coactivator 7 Nucleus transcription regulator up 0.04 0.60 0.21 ILMN_1687768 NCOA7 up 0.00 0.38 0.29 22025508 MYD88-dependent recruitment of inflammatory monocytes and dendritic cells to the lungs are key initial cellular responses required for early protection from Burkholderia mallei infection. (Demonstrated in mice) 11755471_a_at NECAB2 N-terminal EF-hand calcium binding protein 2 Cytoplasm other down 0.00 -1.08 0.87 ILMN_1663437 NECAB2 down 0.00 -0.70 0.65 22386951 MYD88 deficiency results in delayed recruitment of phagocytes and defective production of proinflammatory cytokines in response to Salmonella infection. (Demonstrated in mice) 11726796_a_at NEXN nexilin (F actin binding protein) Plasma Membrane other up 0.00 0.84 0.19 ILMN_1783276 NEXN up 0.00 0.54 0.55 22491177 MYD88 signalling in intestinal epithelial cells is crucial for the maintenance of gut microbiota homeostasis. (Demonstrated in mice) 11726797_x_at NEXN nexilin (F actin binding protein) Plasma Membrane other up 0.00 0.81 0.12 22536449 MYD88 mediated production of reactive oxygen species (ROS) is essential for the induction of IL12 by lactic acid bacteria. (Demonstrated in mice) 11726798_a_at NEXN nexilin (F actin binding protein) Plasma Membrane other up 0.00 1.04 0.92 22377803 NAMPT secretion is enhanced by extracellular ATP in LPS-primed monocytes. 11746008_x_at NEXN nexilin (F actin binding protein) Plasma Membrane other up 0.00 0.89 0.89 11749172_x_at NEXN nexilin (F actin binding protein) Plasma Membrane other up 0.00 0.89 0.25 11754911_x_at NEXN nexilin (F actin binding protein) Plasma Membrane other up 0.00 0.90 0.80 11725210_s_at NFXL1 nuclear transcription factor, X-box binding-like 1 Nucleus transcription regulator up 0.00 0.78 0.69 ILMN_1682197 NFXL1 up 0.00 0.37 1.12 11756155_a_at NHS Nance-Horan syndrome (congenital cataracts and dental anomalies) Nucleus other down 0.01 -0.73 1.09 ILMN_1715864 NHS down 0.00 -0.62 1.19 11724497_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0.02 0.97 1.17 ILMN_1733581 NPRL3 up 0.00 0.72 0.97 11748257_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0.00 1.05 1.17 11753912_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0.00 1.02 1.17 11763176_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0.01 1.00 1.17 21750107 The Glucocorticoid receptor, NR3C1, exerts anti-inflammatory action in part by antagonizing pro-inflammatory transcription factors such as RELA of the NFkB complex. 11735194_a_at NR3C1 nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) Nucleus ligand-dependent nuclear receptorrimexolone, medrysone,down clocortolone pivalate, diflorasone diacetate,0.03 fluorometholone,-0.42 dexamethasone phosphate,1.08 cortisone ILMN_2389347 acetate, halcinonide,NR3C1 flurandrenolide,down desoximetasone, desonide, prednisolone,0.00 clobetasol propionate, fluocinolone-0.33 acetonide, prednisone,1.14 NR3C1 hydrocortisone,21940629 triamcinolone, NR3C1, dexamethasone the glucocorticoid 21-acetate, receptor, 11beta is necessary hydrocortisone for glucocorticoid-mediated acetate, betamethasone, induction dexamethasone, of NLRP3 and budesonide, the subsequent fluticasone, formation beclomethasone of inflammasomes, dipropionate, demonstrating acetic acid/hydrocortisone,a novel role for glucocorticoids betamethasone in sensitizing acetate/betamethasone the initial inflammatory phosphate, response betamethasone by the innate acetate, immune triamcinolone system. (Demonstrated acetonide, ciprofloxacin/hydrocortisone, in mice) dexamethasone/neomycin/polymyxin B, ciprofloxacin/dexamethasone, ORG 34517, ciclesonide, betamethasone dipropionate/calcipotriene, fluticasone furoate, budesonide/formoterol, difluprednate, formoterol/mometasone furoate, azelastine/fluticasone propionate, beclomethasone 17-monopropionate, clotrimazole/betamethasone dipropionate, fluticasone/salmeterol, dexamethasone/tobramycin, clotrimazole/betamethasone, miconazole, prednisolone acetat 11742425_a_at NR3C1 nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) Nucleus ligand-dependent nuclear receptorrimexolone, medrysone,down clocortolone pivalate, diflorasone diacetate,0.01 fluorometholone,-0.47 dexamethasone phosphate,1.03 cortisone acetate, halcinonide, flurandrenolide, desoximetasone, desonide, prednisolone, clobetasol propionate, fluocinolone acetonide, prednisone, hydrocortisone, triamcinolone, dexamethasone 21-acetate, 11beta hydrocortisone acetate, betamethasone, dexamethasone, budesonide, fluticasone, beclomethasone dipropionate, acetic acid/hydrocortisone, betamethasone acetate/betamethasone phosphate, betamethasone acetate, triamcinolone acetonide, ciprofloxacin/hydrocortisone, dexamethasone/neomycin/polymyxin B, ciprofloxacin/dexamethasone, ORG 34517, ciclesonide, betamethasone dipropionate/calcipotriene, fluticasone furoate, budesonide/formoterol, difluprednate, formoterol/mometasone furoate, azelastine/fluticasone propionate, beclomethasone 17-monopropionate, clotrimazole/betamethasone dipropionate, fluticasone/salmeterol, dexamethasone/tobramycin, clotrimazole/betamethasone, miconazole, prednisolone acetat 11718787_at NRGN neurogranin (protein kinase C substrate, RC3) Cytoplasm other up 0.00 0.93 1.11 ILMN_1705686 NRGN up 0.00 0.67 0.47 Page 79 of 111 Diabetes

11732365_a_at NT5C3 5-nucleotidase, cytosolic III Cytoplasm phosphatase up 0.02 0.42 0.24 ILMN_2352121 NT5C3 up 0.00 0.40 0.17 ILMN_1769734 NT5C3 up 0.00 0.36 0.68 11756899_a_at NUDT21 nudix (nucleoside diphosphate linked moiety X)-type motif 21 Nucleus other down 0.00 -0.65 1.15 ILMN_1798886 NUDT21 down 0.02 -0.44 0.36 11732403_a_at OGFRL1 opioid growth factor receptor-like 1 unknown other down 0.01 -0.61 1.10 ILMN_1715809 OGFRL1 down 0.00 -0.43 1.12 11760590_x_at OGFRL1 opioid growth factor receptor-like 1 unknown other down 0.01 -0.62 1.13 11757614_s_at OPA1 optic atrophy 1 (autosomal dominant) Cytoplasm enzyme down 0.03 -0.54 1.13 ILMN_1729775 OPA1 down 0.00 -0.44 1.20 11736300_a_at ORMDL1 ORM1-like 1 (S. cerevisiae) Cytoplasm other down 0.01 -0.52 0.13 ILMN_2045975 ORMDL1 down 0.03 -0.31 1.08 11735165_s_at OSBPL5 oxysterol binding protein-like 5 Cytoplasm other up 0.02 0.63 0.93 ILMN_1802151 OSBPL5 up 0.00 0.47 0.94 11735166_x_at OSBPL5 oxysterol binding protein-like 5 Cytoplasm other up 0.02 0.58 1.08 ILMN_2307032 OSBPL5 up 0.00 0.52 1.18 11743412_at OTUD1 OTU domain containing 1 unknown other down 0.03 -0.45 1.17 ILMN_1752008 OTUD1 down 0.00 -0.44 1.17 ILMN_1723141 OTUD1 down 0.00 -0.34 1.11 11723734_s_at OTUD6B OTU domain containing 6B unknown other down 0.01 -0.72 0.88 ILMN_2215631 OTUD6B down 0.00 -0.50 0.83 11723341_x_at OXR1 oxidation resistance 1 Cytoplasm other down 0.00 -0.69 1.13 ILMN_1737462 OXR1 down 0.00 -0.74 0.43 11730955_a_at P2RX1 purinergic receptor P2X, ligand-gated ion channel, 1 Plasma Membrane ion channel down 0.01 -0.49 1.13 ILMN_1758529 P2RX1 down 0.02 -0.38 1.19 11730956_a_at P2RX1 purinergic receptor P2X, ligand-gated ion channel, 1 Plasma Membrane ion channel down 0.00 -0.66 1.16 11727596_a_at PADI2 peptidyl arginine deiminase, type II Cytoplasm enzyme down 0.03 -0.74 0.91 ILMN_1771223 PADI2 down 0.03 -0.50 0.40 11727597_at PADI2 peptidyl arginine deiminase, type II Cytoplasm enzyme down 0.00 -0.83 0.89 11745141_a_at PADI2 peptidyl arginine deiminase, type II Cytoplasm enzyme down 0.01 -0.75 0.98 11752300_a_at PADI2 peptidyl arginine deiminase, type II Cytoplasm enzyme down 0.01 -0.98 0.59 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme down 0.01 -0.52 1.07 ILMN_2313901 PAM down 0.01 -0.45 0.26 11743829_a_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme down 0.03 -0.48 1.04 11743830_a_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme down 0.03 -0.59 1.10 11746357_s_at PARG poly (ADP-ribose) glycohydrolase Cytoplasm enzyme down 0.04 -0.60 1.16 ILMN_1694752 PARG down 0.04 -0.43 1.14 11724188_x_at PARP10 poly (ADP-ribose) polymerase family, member 10 Nucleus other up 0.00 0.67 0.71 ILMN_2262044 PARP10 up 0.00 0.77 0.09 11747910_a_at PARP10 poly (ADP-ribose) polymerase family, member 10 Nucleus other up 0.04 0.51 1.04 ILMN_1710844 PARP10 up 0.03 0.39 1.18 11757624_s_at PARP12 poly (ADP-ribose) polymerase family, member 12 Nucleus other up 0.01 0.53 0.22 ILMN_1718558 PARP12 up 0.00 0.42 0.21 11759895_at PCDH9 protocadherin 9 Plasma Membrane other down 0.03 -0.62 0.19 ILMN_1752294 PCDH9 down 0.03 -0.49 1.10 11722295_at PCF11 PCF11, cleavage and polyadenylation factor subunit, homolog (S. cerevisiae)Nucleus other down 0.01 -0.63 1.08 ILMN_1798602 PCF11 down 0.00 -0.46 1.20 11718735_at PCMTD1 protein-L-isoaspartate (D-aspartate) O-methyltransferase domain containingCytoplasm 1 enzyme down 0.00 -0.70 1.13 ILMN_1737426 PCMTD1 down 0.02 -0.48 0.99 11742046_a_at PCMTD2 protein-L-isoaspartate (D-aspartate) O-methyltransferase domain containingCytoplasm 2 enzyme down 0.01 -0.64 1.08 ILMN_1767848 PCMTD2 down 0.00 -0.64 0.11 11734957_a_at PCNXL4 pecanex-like 4 (Drosophila) unknown other down 0.02 -0.57 0.79 ILMN_2111918 PCNXL4 down 0.00 -0.48 0.71 11734958_s_at PCNXL4 pecanex-like 4 (Drosophila) unknown other down 0.04 -0.58 1.00 ILMN_1680781 PCNXL4 down 0.01 -0.45 0.17 11756695_x_at PCNXL4 pecanex-like 4 (Drosophila) unknown other down 0.02 -0.54 1.12 11722231_at PDP1 pyruvate dehyrogenase phosphatase catalytic subunit 1 Cytoplasm phosphatase down 0.00 -0.65 1.14 ILMN_2218780 PDP1 down 0.00 -0.47 1.16 19734906 PELI1 is a ubiquitin ligase that facilitates TRIF-dependent Toll-like receptor signalling and pro-inflammatory cytokine production. 11730906_at PDS5B PDS5, regulator of cohesion maintenance, homolog B (S. cerevisiae) Nucleus other down 0.02 -0.58 1.16 ILMN_1746696 PDS5B down 0.01 -0.47 0.33 17997719 PELI1 (pellino) isoforms are E3 ubiquitin ligases that mediate the IL-1-stimulated formation of K63-pUb-IRAK1 in cells, contributing to the activation of IKBKB and NF-kappaB, as well as other signalling pathways dependent on IRAK1 and IRAK4. 11745912_a_at PELI1 pellino E3 ubiquitin protein ligase 1 Cytoplasm enzyme down 0.04 -0.80 1.10 ILMN_1679268 PELI1 down 0.01 -0.53 0.87 PELI1 20171181 Discrete regions of PELI1 are bound by SMAD6 and SMAD7 via their MH2 domains to mediate TGF-beta1-induced negative regulation of IL-1R/TLR signalling. 11722405_at PFKFB4 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 Cytoplasm kinase down 0.05 -0.64 1.12 ILMN_1653292 PFKFB4 down 0.00 -0.61 1.15 21120624 PELI1 is an adaptor protein involved in IL1R/TLR signaling. PELI1 is sumoylated by SUMO1at 5 lysine residues, and binds to the SUMO-conjugating enzyme UBE2I. 11731074_at PGGT1B protein geranylgeranyltransferase type I, beta subunit Cytoplasm enzyme down 0.00 -0.45 1.16 ILMN_1913336 PGGT1B down 0.05 -0.39 1.02 11729607_at PGM2 phosphoglucomutase 2 Cytoplasm enzyme down 0.01 -0.55 1.06 ILMN_1673543 PGM2 down 0.00 -0.42 1.21 11752696_a_at PGM2 phosphoglucomutase 2 Cytoplasm enzyme down 0.03 -0.52 1.02 11758556_s_at PGM2 phosphoglucomutase 2 Cytoplasm enzyme down 0.00 -0.68 1.10 11755359_x_at PHACTR4 phosphatase and actin regulator 4 Plasma Membrane other up 0.00 0.53 1.02 ILMN_1736548 PHACTR4 up 0.04 0.39 1.01 11751640_a_at PHF11 PHD finger protein 11 unknown other up 0.00 0.50 0.37 ILMN_1776723 PHF11 up 0.00 0.45 0.38 11751641_x_at PHF11 PHD finger protein 11 unknown other up 0.04 0.47 0.42 11727529_at PHF20L1 PHD finger protein 20-like 1 unknown other down 0.00 -0.63 1.11 ILMN_1732985 PHF20L1 down 0.00 -0.43 1.18 11727531_at PHF20L1 PHD finger protein 20-like 1 unknown other down 0.01 -0.63 1.07 11733293_at PHF20L1 PHD finger protein 20-like 1 unknown other down 0.05 -0.57 1.12 11733294_at PHF20L1 PHD finger protein 20-like 1 unknown other down 0.05 -0.68 0.64 11720359_at PHIP pleckstrin homology domain interacting protein Nucleus other down 0.03 -0.56 0.87 ILMN_1898682 PHIP updown 0.04 0.02 0.51 -0.49 0.69 0.98 11720361_at PHIP pleckstrin homology domain interacting protein Nucleus other down 0.02 -0.54 1.12 11720362_at PHIP pleckstrin homology domain interacting protein Nucleus other down 0.04 -0.52 1.15 11725271_a_at PIGA phosphatidylinositol glycan anchor biosynthesis, class A Cytoplasm enzyme down 0.00 -0.61 1.16 ILMN_1705985 PIGA down 0.00 -0.65 0.64 ILMN_1802390 PIGA down 0.01 -0.46 0.65 17827709 PIK3R1 (p85-alpha) is a subunit of phosphoinositide 3-kinase (PI3K) and PI3K is activated upon Toll-like receptor (TLR) ligation. 11739540_a_at PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) Cytoplasm kinase down 0.00 -0.71 0.86 ILMN_1691433 PIK3R1 down 0.02 -0.54 0.52 PIK3R1 16921024 PIK3R1 interacts with SYK during Fc-gamma receptor phagocytosis and endocytosis. 11728424_x_at PILRA paired immunoglobin-like type 2 receptor alpha Plasma Membrane other down 0.03 -0.57 1.05 ILMN_2362858 PILRA down 0.00 -0.55 1.22 ILMN_1729915 PILRA down 0.01 -0.52 1.17 ILMN_2241953 PILRA down 0.01 -0.59 0.60 11749074_a_at PISD phosphatidylserine decarboxylase Cytoplasm enzyme down 0.04 -0.59 1.16 ILMN_1793934 PISD down 0.00 -0.45 0.19 11719113_a_at PJA2 praja ring finger 2, E3 ubiquitin protein ligase Cytoplasm enzyme down 0.04 -0.55 1.11 ILMN_1688702 PJA2 down 0.04 -0.50 0.22 11719114_a_at PJA2 praja ring finger 2, E3 ubiquitin protein ligase Cytoplasm enzyme down 0.03 -0.55 1.07 11738053_x_at PLAUR plasminogen activator, urokinase receptor Plasma Membrane transmembrane receptor down 0.02 -0.69 1.10 ILMN_2374340 PLAUR down 0.01 -0.40 1.15 PLAUR 21998707 PLAUR is required for optimal TLR2-induced neutrophil activation. (Demonstrated in mice) 11742818_a_at PLAUR plasminogen activator, urokinase receptor Plasma Membrane transmembrane receptor down 0.03 -0.70 1.17 11743062_a_at PLAUR plasminogen activator, urokinase receptor Plasma Membrane transmembrane receptor down 0.03 -0.81 1.13 11743063_x_at PLAUR plasminogen activator, urokinase receptor Plasma Membrane transmembrane receptor down 0.02 -0.66 1.14 11728571_a_at PLCL1 phospholipase C-like 1 Cytoplasm enzyme down 0.03 -0.48 0.27 ILMN_2206953 PLCL1 down 0.02 -0.52 1.19 11745090_a_at PLXDC2 plexin domain containing 2 Extracellular Space other down 0.02 -0.69 1.13 ILMN_1753312 PLXDC2 down 0.00 -0.69 1.13 11724509_a_at PMAIP1 phorbol-12-myristate-13-acetate-induced protein 1 Cytoplasm other down 0.00 -0.93 1.15 ILMN_2098446 PMAIP1 down 0.02 -0.47 1.11 PMAIP1 21698224 PMAIP1 is induced by the RIG-I/MDA5 axis during viral infection and activates apoptosis in macrophages, dendritic cells and primary lymphocytes. 11724510_at PMAIP1 phorbol-12-myristate-13-acetate-induced protein 1 Cytoplasm other down 0.00 -0.96 1.17 11726875_a_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.01 0.51 1.02 ILMN_1728019 PML up 0.03 0.33 1.12 PML 21131187 PML, a member of the TRIM protein family, is upregulated by Type I and Type II interferons and have been found to restrict viral replication by modulating the RIG-I pathway. 11726876_a_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.00 0.74 0.22 21779477 Pml(-/-) mice are resistant to LPS-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-kB pathway. Pml(-/-) mice also exhibit impaired function of macrophages and are thus unable to clear pathogenic microorganisms. (Demonstrated in murine model) 11728557_s_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.00 0.88 0.13 11729443_a_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.00 0.71 0.63 11741878_a_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.00 0.88 0.76 11741879_x_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.00 0.67 0.73 11751251_a_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.00 0.73 0.28 11720672_a_at PPM1A protein phosphatase, Mg2+/Mn2+ dependent, 1A Cytoplasm phosphatase down 0.02 -0.51 1.09 ILMN_1903159 PPM1A down 0.04 -0.33 1.18 11726945_at PPM1A protein phosphatase, Mg2+/Mn2+ dependent, 1A Cytoplasm phosphatase down 0.00 -0.64 1.17 11719712_at PPM1B protein phosphatase, Mg2+/Mn2+ dependent, 1B Cytoplasm phosphatase down 0.00 -0.53 1.16 ILMN_1734991 PPM1B up 0.00 0.48 1.18 11725259_s_at PPM1B protein phosphatase, Mg2+/Mn2+ dependent, 1B Cytoplasm phosphatase down 0.00 -0.57 1.13 ILMN_1716862 PPM1B down 0.00 -0.48 0.90 11746099_a_at PPP4R1 protein phosphatase 4, regulatory subunit 1 unknown phosphatase down 0.02 -0.58 1.02 ILMN_1724544 PPP4R1 down 0.04 -0.41 1.21 ILMN_2345512 PPP4R1 down 0.00 -0.45 1.14 11746892_a_at PPWD1 peptidylprolyl isomerase domain and WD repeat containing 1 Nucleus enzyme down 0.04 -0.64 1.00 ILMN_2223380 PPWD1 down 0.01 -0.48 1.03 11718391_a_at PREPL prolyl endopeptidase-like unknown peptidase down 0.03 -0.62 1.06 ILMN_1666615 PREPL down 0.02 -0.41 0.62 11718393_s_at PREPL prolyl endopeptidase-like unknown peptidase down 0.01 -0.62 1.13 ILMN_2345319 PREPL down 0.04 -0.36 1.11 11730261_a_at PRKAR2B protein kinase, cAMP-dependent, regulatory, type II, beta Cytoplasm kinase up 0.04 0.62 0.81 ILMN_1684850 PRKAR2B up 0.04 0.41 0.21 11735731_a_at PRKRIR protein-kinase, interferon-inducible double stranded RNA dependent inhibitor,Nucleus repressor of (P58 otherrepressor) down 0.02 -0.68 1.17 ILMN_1655622 PRKRIR down 0.03 -0.52 0.26 11732808_a_at PROK2 prokineticin 2 Extracellular Space other down 0.00 -1.58 1.09 ILMN_1775257 PROK2 down 0.00 -1.05 1.21 11732809_a_at PROK2 prokineticin 2 Extracellular Space other down 0.00 -1.24 1.15 11763818_x_at PRR5 proline rich 5 (renal) unknown other up 0.03 0.66 1.16 ILMN_2409754 PRR5 up 0.00 0.61 1.03 11755296_a_at PSAP prosaposin Extracellular Space other down 0.02 -0.61 1.16 ILMN_1749109 PSAP down 0.02 -0.43 1.07 11761869_at PSIP1 PC4 and SFRS1 interacting protein 1 Nucleus other up 0.00 0.83 1.12 ILMN_1788701 PSIP1 up 0.02 0.52 0.15 11720983_s_at PSMC6 proteasome (prosome, macropain) 26S subunit, ATPase, 6 Nucleus peptidase down 0.05 -0.75 1.03 ILMN_1655316 PSMC6 down 0.04 -0.43 1.05 11732180_a_at PTAFR platelet-activating factor receptor Plasma Membrane G-protein coupled receptor lexipafant down 0.01 -0.73 1.14 ILMN_1746836 PTAFR down 0.00 -0.48 0.93 PTAFR 11309383 PTAFR is involved in G-protein-independent activation of TYK2. 11722804_x_at PTBP2 polypyrimidine tract binding protein 2 Nucleus other down 0.00 -0.78 0.88 ILMN_2142979 PTBP2 down 0.00 -0.51 1.05 11758115_s_at PTBP2 polypyrimidine tract binding protein 2 Nucleus other down 0.00 -0.72 0.78 ILMN_1707240 PTBP2 down 0.00 -0.48 1.10 11731884_x_at PTCRA pre T-cell antigen receptor alpha Cytoplasm other up 0.00 0.69 1.02 ILMN_2091920 PTCRA up 0.04 0.33 1.16 11735589_at PTGDR prostaglandin D2 receptor (DP) Plasma Membrane G-protein coupled receptor down 0.01 -0.48 0.51 ILMN_1706268 PTGDR down 0.02 -0.34 0.86 11724037_at PTGS2 prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)Cytoplasm enzyme acetaminophen/pentazocine,down acetaminophen/clemastine/pseudoephedrine,0.01 aspirin/butalbital/caffeine,-0.78 acetaminophen/caffeine/dihydrocodeine,1.17 ILMN_2054297 PTGS2 aspirin/hydrocodone,down aspirin/oxycodone, acetaminophen/aspirin/caffeine,0.00 aspirin/pravastatin,-0.64 acetaminophen/dexbrompheniramine/pseudoephedrine,0.85 PTGS2 18955820 PTGS2 (COX-2) aspirin/meprobamate, is suppressed through aspirin/caffeine/propoxyphene, inhibiting the NF-kappaB activationaspirin/butalbital/caffeine/codeine, by LPS and this may be associated aspirin/caffeine/dihydrocodeine, with the anti-inflammatory chlorpheniramine/ibuprofen/pseudoephedrine, effects of L. casei on Raw264.7 cells. licofelone, menatetrenone, suprofen, tiaprofenic acid, tenoxicam, naproxen/sumatriptan, ibuprofen/phenylephrine/chlorpheniramine, diclofenac/misoprostol, acetaminophen/butalbital/caffeine, hydrocodone/ibuprofen, acetaminophen/hydrocodone, acetaminophen/tramadol, acetaminophen/codeine, acetaminophen/oxycodone, acetaminophen/propoxyphene, nitroaspirin, ketoprofen, diclofenac, naproxen, meclofenamic acid, meloxicam, celecoxib, dipyrone, acetaminophen, mefenamic acid, diflunisal, ibuprofen, GW406381X, indomethacin, sulfasalazine, piroxicam, valdecoxib, aspirin, zomepirac, rof ILMN_1677511 PTGS2 down 0.02 -0.40 1.09 11725685_a_at PTPRO protein tyrosine phosphatase, receptor type, O Plasma Membrane phosphatase down 0.03 -0.72 1.01 ILMN_1720113 PTPRO down 0.01 -0.51 1.18 11719302_a_at PYGL phosphorylase, glycogen, liver Cytoplasm enzyme down 0.03 -0.82 1.17 ILMN_1696187 PYGL down 0.04 -0.46 0.62 11719827_a_at QPCT glutaminyl-peptide cyclotransferase Cytoplasm enzyme down 0.01 -0.76 1.14 ILMN_1741727 QPCT down 0.00 -0.89 1.22 11719828_x_at QPCT glutaminyl-peptide cyclotransferase Cytoplasm enzyme down 0.02 -0.78 1.14 11718030_at RAB11A RAB11A, member RAS oncogene family Cytoplasm enzyme down 0.02 -0.48 1.02 ILMN_1712312 RAB11A down 0.00 -0.56 0.32 RAB11A 20933442 RAB11A is an important regulator of Toll-like receptor 4 (TLR4) and TRAM transport to E. coli phagosomes thereby controlling IRF3 activation from this compartment. 11751326_a_at RAB11A RAB11A, member RAS oncogene family Cytoplasm enzyme down 0.00 -0.67 1.06 11724141_a_at RAB11FIP2 RAB11 family interacting protein 2 (class I) Cytoplasm other down 0.01 -0.63 0.96 ILMN_2072541 RAB11FIP2 down 0.00 -0.45 1.22 11724142_s_at RAB11FIP2 RAB11 family interacting protein 2 (class I) Cytoplasm other down 0.00 -0.56 1.11 ILMN_1741175 RAB11FIP2 down 0.00 -0.45 0.72 11724143_s_at RAB11FIP2 RAB11 family interacting protein 2 (class I) Cytoplasm other down 0.00 -0.59 0.94 11725426_a_at RAB27A RAB27A, member RAS oncogene family Cytoplasm enzyme down 0.04 -0.57 1.05 ILMN_2329773 RAB27A down 0.04 -0.36 0.57 ILMN_1665859 RAB27A down 0.00 -0.47 0.39 11721421_s_at RAP1GAP2 RAP1 GTPase activating protein 2 Cytoplasm other down 0.02 -0.19 0.08 ILMN_2041236 RAP1GAP2 down 0.00 -0.51 0.53 11749458_a_at RAP1GAP2 RAP1 GTPase activating protein 2 Cytoplasm other down 0.01 -0.49 0.13 11719402_a_at RAP2A RAP2A, member of RAS oncogene family Plasma Membrane enzyme down 0.03 -0.63 1.13 ILMN_1677404 RAP2A down 0.02 -0.39 0.28 11743480_s_at RB1CC1 RB1-inducible coiled-coil 1 Nucleus other down 0.00 -0.64 1.12 ILMN_1736796 RB1CC1 down 0.00 -0.58 0.41 11743481_at RB1CC1 RB1-inducible coiled-coil 1 Nucleus other down 0.00 -0.69 1.15 11735723_s_at RBCK1 RanBP-type and C3HC4-type zinc finger containing 1 Cytoplasm transcription regulator up 0.04 0.50 1.15 ILMN_1751330 RBCK1 up 0.01 0.53 0.49 RBCK1 19136968 RBCK1 (LUBAC) complexes with RNF31 and is involved in the physiological regulation of the canonical NF-kappaB activation pathway through linear polyubiquitylation of IKBKG. 11756449_x_at RBCK1 RanBP-type and C3HC4-type zinc finger containing 1 Cytoplasm transcription regulator up 0.01 0.63 1.03 ILMN_2406313 RBCK1 up 0.03 0.49 0.14 11740390_a_at RBM47 RNA binding motif protein 47 unknown other down 0.01 -0.81 1.16 ILMN_1689046 RBM47 down 0.00 -0.51 1.09 11755523_a_at RBM47 RNA binding motif protein 47 unknown other down 0.00 -0.86 1.08 11757532_s_at RBM47 RNA binding motif protein 47 unknown other down 0.02 -0.69 1.17 11725237_a_at RBPMS2 RNA binding protein with multiple splicing 2 unknown other up 0.00 1.15 0.84 ILMN_1808238 RBPMS2 up 0.00 0.85 1.17 11719334_a_at RCBTB1 regulator of chromosome condensation (RCC1) and BTB (POZ) domain containingNucleus protein 1 other down 0.00 -0.72 0.58 ILMN_1695317 RCBTB1 down 0.00 -0.46 0.63 11756563_a_at RCBTB2 regulator of chromosome condensation (RCC1) and BTB (POZ) domain containingunknown protein 2 other down 0.02 -0.63 1.07 ILMN_2148668 RCBTB2 down 0.02 -0.48 1.15 11729123_a_at RCN2 reticulocalbin 2, EF-hand calcium binding domain Cytoplasm other down 0.05 -0.96 0.67 ILMN_1662129 RCN2 down 0.00 -0.60 0.98 11732251_s_at RCOR3 REST corepressor 3 Nucleus other down 0.04 -0.46 1.17 ILMN_1682095 RCOR3 down 0.00 -0.39 0.20 11732252_x_at RCOR3 REST corepressor 3 Nucleus other down 0.00 -0.63 1.13 11757795_s_at RCOR3 REST corepressor 3 Nucleus other down 0.03 -0.49 1.17 11717525_s_at RDX radixin Cytoplasm other down 0.01 -0.56 1.09 ILMN_1708611 RDX down 0.03 -0.35 0.93 11727910_a_at RELT RELT tumor necrosis factor receptor Plasma Membrane transmembrane receptor down 0.03 -0.52 1.02 ILMN_1748614 RELT down 0.00 -0.68 1.11 11722347_a_at REPS2 RALBP1 associated Eps domain containing 2 Cytoplasm other down 0.03 -0.80 1.12 ILMN_1766425 REPS2 down 0.03 -0.40 1.21 11722348_a_at REPS2 RALBP1 associated Eps domain containing 2 Cytoplasm other down 0.02 -0.73 1.01 ILMN_2405797 REPS2 down 0.00 -0.61 0.33 ILMN_1656934 REPS2 down 0.03 -0.54 0.46 11739797_a_at RFX2 regulatory factor X, 2 (influences HLA class II expression) Nucleus transcription regulator down 0.02 -1.01 1.17 ILMN_1706357 RFX2 down 0.00 -0.64 1.17 11755653_a_at RFX2 regulatory factor X, 2 (influences HLA class II expression) Nucleus transcription regulator down 0.02 -1.01 1.17 11743189_a_at RGL1 ral guanine nucleotide dissociation stimulator-like 1 Cytoplasm other up 0.00 0.47 0.65 ILMN_1654398 RGL1 up 0.00 0.50 0.64 11757824_s_at RGL1 ral guanine nucleotide dissociation stimulator-like 1 Cytoplasm other up 0.00 0.54 0.66 11729758_at RGS18 regulator of G-protein signaling 18 Cytoplasm other down 0.00 -0.86 1.09 ILMN_2101278 RGS18 down 0.00 -0.66 1.21 11729759_at RGS18 regulator of G-protein signaling 18 Cytoplasm other down 0.00 -0.70 1.09 11717688_a_at RNF19A ring finger protein 19A, E3 ubiquitin protein ligase Nucleus enzyme down 0.01 -0.50 1.14 ILMN_2381197 RNF19A down 0.00 -0.48 1.07 11717689_a_at RNF19A ring finger protein 19A, E3 ubiquitin protein ligase Nucleus enzyme down 0.01 -0.64 1.02 11724595_at RP2 retinitis pigmentosa 2 (X-linked recessive) Cytoplasm enzyme down 0.00 -0.76 1.07 ILMN_1659255 RP2 down 0.00 -0.59 0.61 11726119_at RPGR retinitis pigmentosa GTPase regulator Cytoplasm other down 0.00 -0.85 1.11 ILMN_2336803 RPGR down 0.03 -0.37 1.14 11757329_s_at RPL26 ribosomal protein L26 Cytoplasm other up 0.01 1.17 0.84 ILMN_1731546 RPL26 up 0.00 1.08 0.38 11715238_x_at RPL9 ribosomal protein L9 Cytoplasm other down 0.02 -0.72 0.74 ILMN_2408415 RPL9 up 0.00 0.97 0.12 11758357_x_at RPL9 ribosomal protein L9 Cytoplasm other down 0.04 -0.97 0.62 ILMN_1750507 RPL9 down 0.01 -0.74 0.10 ILMN_1729033 RPL9 down 0.04 -0.57 1.11 11723251_at RPS15A ribosomal protein S15a Cytoplasm other up 0.03 0.93 1.03 ILMN_2337241 RPS15A up 0.00 0.74 0.21 ILMN_2255310 RPS15A up 0.00 0.98 0.17 ILMN_1787949 RPS15A updown 0.01 0.02 0.87 -0.96 0.50 0.48 11719784_x_at RPS23 ribosomal protein S23 Cytoplasm translation regulator down 0.00 -0.57 0.61 ILMN_1772459 RPS23 down 0.00 -0.56 0.07 11757021_x_at RPS24 ribosomal protein S24 Cytoplasm other up 0.03 0.99 0.68 ILMN_1656625 RPS24 up 0.01 0.80 0.09 200061_PM_s_at RPS24 ribosomal protein S24 Cytoplasm other up 0.04 0.96 0.74 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other down 0.00 -0.89 1.14 ILMN_2209027 RPS26 down 0.00 -0.92 0.96 11744350_a_at RPS27L ribosomal protein S27-like Nucleus other up 0.01 1.10 0.83 ILMN_1712678 RPS27L up 0.00 0.62 0.61 11716320_x_at RPS3A ribosomal protein S3A Cytoplasm other down 0.03 -0.70 0.56 ILMN_1673638 RPS3A up 0.00 1.00 0.18 200099_PM_s_at RPS3A ribosomal protein S3A Cytoplasm other down 0.02 -0.68 0.45 ILMN_2139943 RPS3A updown 0.01 0.01 1.01 -1.08 0.59 0.17 ILMN_1657722 RPS3A updown 0.00 0.04 0.97 -0.84 0.22 0.64 11744411_s_at RSL24D1 ribosomal L24 domain containing 1 Nucleus other down 0.01 -1.08 0.91 ILMN_2175465 RSL24D1 down 0.02 -0.65 0.35 11738035_s_at RTN4 reticulon 4 Cytoplasm other down 0.00 -0.73 0.53 ILMN_2352036 RTN4 down 0.04 -0.44 1.21 11743428_a_at RUNX3 runt-related transcription factor 3 Nucleus transcription regulator up 0.01 0.57 1.13 ILMN_1787461 RUNX3 up 0.00 0.48 1.18 RUNX3 16164020 RUNX3 is capable of activating the CD11a gene promoter that directs CD11a/CD18 integrin expression as well as trans-activating the CD49d gene promoter. The leukocyte integrins CD11a/CD18 (LFA-1, alphaLbeta2) and CD49d (VLA-4, alpha4beta1, alpha4beta7) mediate leukocyte transendothelial migration during immune and inflammatory responses and provide co-stimulatory signals for the activation of T lymphocytes. 11755054_x_at RUNX3 runt-related transcription factor 3 Nucleus transcription regulator up 0.03 0.54 1.16 11718347_a_at S100P S100 calcium binding protein P Cytoplasm other down 0.00 -1.14 1.08 ILMN_1801216 S100P down 0.00 -0.86 0.69 11734863_a_at SARNP SAP domain containing ribonucleoprotein Nucleus other up 0.02 0.76 1.11 ILMN_1680967 SARNP up 0.00 0.64 0.88 11733051_a_at SCAMP1 secretory carrier membrane protein 1 Cytoplasm transporter down 0.05 -0.50 1.17 ILMN_1728907 SCAMP1 down 0.00 -0.48 0.83 11715895_at SCARB2 scavenger receptor class B, member 2 Plasma Membrane other up 0.03 0.52 0.65 ILMN_1814726 SCARB2 up 0.00 0.49 0.46 11715896_s_at SCARB2 scavenger receptor class B, member 2 Plasma Membrane other up 0.04 0.70 0.73 11715897_at SCARB2 scavenger receptor class B, member 2 Plasma Membrane other up 0.03 0.50 0.90 11749579_a_at SCARB2 scavenger receptor class B, member 2 Plasma Membrane other up 0.00 0.68 0.24 11732435_at SCIMP SLP adaptor and CSK interacting membrane protein Plasma Membrane other up 0.03 0.45 0.67 ILMN_1682761 SCIMP up 0.00 0.35 1.01 11759298_s_at SCYL2 SCY1-like 2 (S. cerevisiae) Cytoplasm other down 0.01 -0.60 1.11 ILMN_1711919 SCYL2 down 0.01 -0.31 0.50 11718591_at SDF2L1 stromal cell-derived factor 2-like 1 Cytoplasm other up 0.04 0.50 1.08 ILMN_1749213 SDF2L1 up 0.00 0.50 0.50 11732749_at SEC14L5 SEC14-like 5 (S. cerevisiae) unknown other up 0.01 0.85 1.14 ILMN_1687268 SEC14L5 up 0.00 0.60 0.95 11716027_at SELT selenoprotein T Cytoplasm other down 0.00 -0.93 1.07 ILMN_1746368 SELT down 0.01 -0.44 1.15 11716028_x_at SELT selenoprotein T Cytoplasm other down 0.00 -0.90 1.08 11758712_s_at SELT selenoprotein T Cytoplasm other down 0.00 -0.92 1.12 11719102_at SENP6 SUMO1/sentrin specific peptidase 6 Cytoplasm peptidase down 0.00 -0.71 1.13 ILMN_2054233 SENP6 down 0.01 -0.48 0.50 11725849_s_at SENP7 SUMO1/sentrin specific peptidase 7 Nucleus peptidase down 0.00 -0.72 1.15 ILMN_1778294 SENP7 down 0.00 -0.58 0.30 ILMN_2382354 SENP7 down 0.00 -0.52 1.02 11721457_a_at SERPINA1 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), memberExtracellular 1 Space other down 0.00 -0.78 1.17 ILMN_2338452 SERPINA1 down 0.04 -0.51 0.95 ILMN_2404154 SERPINA1 down 0.03 -0.50 1.10 11715931_s_at SGK1 serum/glucocorticoid regulated kinase 1 Cytoplasm kinase down 0.00 -0.61 1.12 ILMN_1702487 SGK1 down 0.00 -0.55 1.01 11733698_s_at SGK1 serum/glucocorticoid regulated kinase 1 Cytoplasm kinase down 0.00 -0.65 1.09 11737749_a_at SGK1 serum/glucocorticoid regulated kinase 1 Cytoplasm kinase down 0.00 -0.80 1.16 11737750_s_at SGK1 serum/glucocorticoid regulated kinase 1 Cytoplasm kinase down 0.00 -0.61 1.08 11718445_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0.01 0.83 0.93 ILMN_1762764 SH3BGRL2 up 0.01 0.34 1.17 11718446_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0.00 0.98 1.03 11718447_s_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0.01 0.93 1.12 11718448_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0.00 0.68 1.17 11744928_x_at SIAH1 siah E3 ubiquitin protein ligase 1 Nucleus enzyme down 0.00 -0.58 1.11 ILMN_1711627 SIAH1 down 0.00 -0.49 0.15 SIAH1 11742346 SIAH1 is a ubiquitin ligase structurally related to TRAF and modulates TNF-alpha signalling. ILMN_2380566 SIAH1 down 0.00 -0.63 1.22 11729739_at SIGLEC5 sialic acid binding Ig-like lectin 5 Plasma Membrane other down 0.00 -0.84 1.17 ILMN_1740298 SIGLEC5 down 0.00 -0.66 0.73 SIGLEC5 19596804 SIGLEC5 is bound by group B Streptococcus (GBS) beta protein and this functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. 11727843_a_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma Membrane1 transporter down 0.01 -0.91 1.15 ILMN_1741165 SLC11A1 down 0.00 -0.80 1.22 21208791 SIGLEC5 is a member of the SIGLEC protein family that recognize sialoside-based patterns and plays a role in the attenuation of innate immunity to avoid autoimmune destruction. 11747774_a_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma Membrane1 transporter down 0.00 -0.95 1.16 11748920_x_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma Membrane1 transporter down 0.00 -1.03 1.07 11724454_at SLC22A4 solute carrier family 22 (organic cation/ergothioneine transporter), memberPlasma 4 Membrane transporter down 0.02 -0.75 1.15 ILMN_2050911 SLC22A4 down 0.00 -0.60 1.19 11759084_a_at SLC30A5 solute carrier family 30 (zinc transporter), member 5 Plasma Membrane transporter down 0.01 -0.69 1.03 ILMN_1664153 SLC30A5 down 0.04 -0.36 0.54 11762300_at SLC35A1 solute carrier family 35 (CMP-sialic acid transporter), member A1 Cytoplasm transporter down 0.00 -0.60 0.79 ILMN_1741440 SLC35A1 down 0.01 -0.37 0.52 11751286_a_at SLC35A5 solute carrier family 35, member A5 unknown transporter down 0.01 -0.56 1.17 ILMN_1709817 SLC35A5 down 0.05 -0.35 0.27 11738999_a_at SLC38A2 solute carrier family 38, member 2 Plasma Membrane transporter down 0.00 -0.62 1.13 ILMN_1651799 SLC38A2 down 0.01 -0.42 1.14 11739000_a_at SLC38A2 solute carrier family 38, member 2 Plasma Membrane transporter down 0.02 -0.43 1.14 11718456_at SLC43A2 solute carrier family 43, member 2 Plasma Membrane transporter down 0.03 -0.67 1.14 ILMN_1787127 SLC43A2 down 0.02 -0.45 1.10 11716270_a_at SLIRP SRA stem-loop interacting RNA binding protein Cytoplasm other up 0.01 0.79 0.78 ILMN_1661945 SLIRP up 0.00 0.68 0.34 11725219_a_at SLK STE20-like kinase Nucleus kinase down 0.01 -0.68 1.14 ILMN_2159322 SLK down 0.00 -0.53 1.18 ILMN_1700834 SLK down 0.00 -0.43 1.18 11739194_s_at SLMAP sarcolemma associated protein Plasma Membrane other down 0.01 -0.48 1.09 ILMN_1783120 SLMAP down 0.00 -0.33 1.13 11725361_s_at SMAD4 SMAD family member 4 Nucleus transcription regulator down 0.02 -0.51 1.15 ILMN_1741477 SMAD4 down 0.00 -0.32 0.43 11750827_a_at SMAD4 SMAD family member 4 Nucleus transcription regulator down 0.03 -0.52 1.16 11729717_a_at SMAD5 SMAD family member 5 Nucleus transcription regulator up 0.03 0.48 1.15 ILMN_1674551 SMAD5 down 0.01 -0.44 1.07 11741023_a_at SMAD5 SMAD family member 5 Nucleus transcription regulator down 0.03 -0.62 1.17 11756552_a_at SMARCAD1 SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin,Nucleus subfamily a, containingenzyme DEAD/H box 1 down 0.03 -0.79 0.92 ILMN_1741976 SMARCAD1 down 0.05 -0.34 1.03 11722657_x_at SMN1/SMN2 survival of motor neuron 1, telomeric Nucleus other down 0.02 -0.46 1.03 ILMN_2336393 SMN1/SMN2 down 0.01 -0.46 1.20 11762978_x_at SMN1/SMN2 survival of motor neuron 1, telomeric Nucleus other down 0.03 -0.51 1.15 11728396_a_at SNX14 sorting nexin 14 unknown transporter down 0.02 -0.53 1.17 ILMN_2361570 SNX14 down 0.00 -0.44 1.16 11730053_a_at SNX16 sorting nexin 16 unknown transporter down 0.00 -1.13 0.99 ILMN_1787415 SNX16 down 0.00 -0.64 0.59 16451196 SOCS1 is a potent and multifaceted regulator of cytokines and cell-mediated inflammation. 11730054_s_at SNX16 sorting nexin 16 unknown transporter down 0.00 -0.90 0.67 19017994 SOCS1 regulates the IFN but Not NF{kappa}B Pathway in TLR-Stimulated Human monocytes and macrophages. 11737146_a_at SOCS1 suppressor of cytokine signaling 1 Cytoplasm other up 0.01 0.57 0.10 ILMN_1774733 SOCS1 up 0.00 0.34 1.15 SOCS1 21263070 SOCS1 is a negative immunomodulator that is upregulated by Hepatitis C virus to deliver negative signalling to TLR-mediated pathways controlling expression of IL12, a key cytokine linking innate and adaptive immunity. 11725024_a_at SOD2 superoxide dismutase 2, mitochondrial Cytoplasm enzyme down 0.02 -0.58 1.17 ILMN_1792922 SOD2 up 0.00 0.35 1.07 21606371 SOCS1 is targeted by endogenous and pharmacologic glucocorticoids to limit TLR3/TLR4-mediated STAT1 activation which results in the suppression of inflammation. (Demonstrated in murine model) ILMN_2406501 SOD2 down 0.01 -0.70 0.15 21757742 SOCS1 inhibits type I interferon (IFN) signaling through an interaction with the IFNAR1 associated kinase, TYK2, resulting in a reduced IFN response and reduced IFNAR1 surface expression. ILMN_2336781 SOD2 down 0.00 -0.81 1.00 11759663_x_at SP100 SP100 nuclear antigen Nucleus transcription regulator up 0.03 0.58 0.61 ILMN_2390586 SP100 up 0.00 0.61 0.06 11728515_a_at SP140 SP140 nuclear body protein Nucleus transcription regulator up 0.03 0.43 0.83 ILMN_1778599 SP140 up 0.04 0.26 0.21 11740248_s_at SPAG1 sperm associated antigen 1 Cytoplasm other down 0.00 -0.51 1.17 ILMN_2367681 SPAG1 down 0.00 -0.48 1.17 11740420_s_at SPAG1 sperm associated antigen 1 Cytoplasm other down 0.00 -0.51 1.14 11725244_a_at SPAST spastin Nucleus enzyme down 0.02 -0.71 1.15 ILMN_2373556 SPAST down 0.01 -0.30 0.68 11736145_a_at SPATA20 spermatogenesis associated 20 unknown other up 0.01 0.58 0.81 ILMN_1687247 SPATA20 up 0.00 0.85 0.22 Diabetes Page 80 of 111

11721115_at SPCS3 signal peptidase complex subunit 3 homolog (S. cerevisiae) Cytoplasm peptidase down 0.02 -0.86 1.17 ILMN_1667707 SPCS3 down 0.01 -0.51 1.11 11741372_x_at SPDYE6 (includes others) speedy homolog E6 (Xenopus laevis) unknown other down 0.03 -0.48 1.17 ILMN_2144654 SPDYE6 (includes others) down 0.04 -0.46 0.32 11723165_a_at SPI1 spleen focus forming virus (SFFV) proviral integration oncogene spi1 Nucleus transcription regulator down 0.04 -0.69 1.11 ILMN_2392043 SPI1 down 0.01 -0.65 0.72 SPI1 20510871 SPI1 (PU.1) directly regulates FLT3 kinase in a concentration-dependent manner, and is a critical regulator of both conventional and plasmacytoid dendritic cell development. ILMN_1696463 SPI1 down 0.00 -0.54 1.12 11758521_s_at SPIRE1 spire homolog 1 (Drosophila) Cytoplasm other down 0.03 -0.58 1.17 ILMN_1757845 SPIRE1 down 0.04 -0.33 1.19 11716525_a_at SPON2 spondin 2, extracellular matrix protein Extracellular Space other up 0.01 0.73 0.53 ILMN_1676099 SPON2 up 0.00 0.59 0.87 SPON2 20205276 SPON2 expression is upregulated during intestinal inflammation and may induce NF-kappaB promoter activation in a TLR-9 mediated manner. 11716526_x_at SPON2 spondin 2, extracellular matrix protein Extracellular Space other up 0.00 0.90 0.60 11754601_s_at SPON2 spondin 2, extracellular matrix protein Extracellular Space other up 0.00 0.96 0.54 11734826_s_at SPRED1 sprouty-related, EVH1 domain containing 1 Plasma Membrane other down 0.00 -1.01 1.13 ILMN_1804277 SPRED1 down 0.00 -0.49 1.14 11722940_a_at SRGAP2 SLIT-ROBO Rho GTPase activating protein 2 Cytoplasm other up 0.00 0.80 0.99 ILMN_1759549 SRGAP2 up 0.04 0.38 1.00 11763263_at SRSF11 serine/arginine-rich splicing factor 11 Nucleus other down 0.01 -0.60 0.64 ILMN_1657790 SRSF11 down 0.00 -0.51 0.59 11743839_a_at ST3GAL6 ST3 beta-galactoside alpha-2,3-sialyltransferase 6 Cytoplasm enzyme down 0.00 -0.91 1.12 ILMN_1781560 ST3GAL6 down 0.00 -0.60 1.14 11731107_a_at STAG2 stromal antigen 2 Nucleus other down 0.00 -0.65 1.13 ILMN_1782609 STAG2 down 0.00 -0.50 0.16 11731108_s_at STAG2 stromal antigen 2 Nucleus other down 0.04 -0.46 1.09 8943351 STAT2 is part of STAT-containing transcription factor, the alpha-interferon-induced ISGF3, that is composed of a STAT1:2 heterodimer and a weak DNA-binding protein, IRF9. 11718652_a_at STAT2 signal transducer and activator of transcription 2, 113kDa Nucleus transcription regulator up 0.01 0.67 0.13 ILMN_1690921 STAT2 up 0.00 0.68 0.17 STAT2 16689942 STAT2 is a critical transactivator component of the interferon-stimulated gene factor 3 (ISGF3) complex that drives the expression of many interferon (IFN)-inducible genes. 11752794_a_at STAT2 signal transducer and activator of transcription 2, 113kDa Nucleus transcription regulator up 0.02 0.58 1.15 23391734 A loss-of-function mutation in STAT2 is associated with increased susceptibility to childhood viral diseases. 11752795_x_at STAT2 signal transducer and activator of transcription 2, 113kDa Nucleus transcription regulator up 0.00 0.78 0.98 17971840 STAT3 is a transcription factor that mediates interleukin-10 (IL-10) cytokine signalling. 11720755_at STAT3 signal transducer and activator of transcription 3 (acute-phase response factor)Nucleus transcription regulator down 0.02 -0.64 1.17 ILMN_2410986 STAT3 down 0.02 -0.54 1.06 STAT3 19667404 STAT3 and SRC have a role in the immunoregulation of dendritic cells (DCs) where apoptotic cells-induced inhibition of dendritic cells (DCs) requires MerTK-dependent activation of SRC and STAT3. ILMN_1663618 STAT3 down 0.03 -0.52 0.71 20040863 STAT3 mediates mucosa-protective and anti-inflammatory functions in epithelial and myeloid cells and promotes inflammation in T cells. ILMN_2401978 STAT3 down 0.03 -0.55 0.67 20493732 STAT3 binds to multiple genes involved in Th17 cell differentiation, cell activation, proliferation, and survival, regulating both expression, epigenetic modifications, and targets the T cell function in inflammation and homeostasis. 11726372_a_at STAU2 staufen, RNA binding protein, homolog 2 (Drosophila) Cytoplasm other down 0.03 -0.57 1.17 ILMN_1769720 STAU2 down 0.01 -0.39 0.30 20581311 STAT3 is an essential mediator of emergency granulopoiesis via its regulation of transcription factors CEBPA and CEBPB that direct granulocyte colony-stimulating factor (G-CSF)-responsive myeloid progenitor expansion. 11729664_s_at STK38L serine/threonine kinase 38 like Cytoplasm kinase down 0.00 -0.78 1.14 ILMN_1755792 STK38L down 0.00 -0.45 1.07 21810606 STAT3 is a negative regulator of type I IFN-mediated anti-viral responses. (Demonstrated in mouse) 11729666_at STK38L serine/threonine kinase 38 like Cytoplasm kinase down 0.00 -0.51 1.03 11737168_a_at STRN3 striatin, calmodulin binding protein 3 Nucleus transcription regulator down 0.00 -0.54 1.07 ILMN_1772946 STRN3 down 0.01 -0.47 0.96 11743882_a_at STRN3 striatin, calmodulin binding protein 3 Nucleus transcription regulator down 0.00 -0.63 1.15 11743633_a_at STX2 syntaxin 2 Cytoplasm transporter down 0.01 -0.60 1.13 ILMN_1747775 STX2 down 0.00 -0.61 0.11 ILMN_2344216 STX2 down 0.00 -0.50 1.22 11747878_a_at STX3 syntaxin 3 Plasma Membrane transporter down 0.04 -0.67 1.15 ILMN_1659544 STX3 down 0.01 -0.44 1.20 11720598_x_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator up 0.04 1.41 1.02 ILMN_1736054 SUB1 updown 0.01 0.01 0.56 -0.52 1.16 0.91 11758245_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator up 0.01 1.22 1.15 11720599_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.00 -0.77 0.86 11751297_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.00 -0.78 0.98 11756654_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.03 -0.70 1.06 11739486_at SUZ12 suppressor of zeste 12 homolog (Drosophila) Nucleus enzyme down 0.02 -0.59 1.11 ILMN_1797813 SUZ12 down 0.04 -0.41 0.12 17283140 TAX1BP1 is a nuclear receptor co-activator that forms a complex with the glucocorticoid receptor (NR3C1). TAX1BP1 can bind Tax, a human T-cell leukemia virus type 1 oncoprotein, directly and this induces the dissociation of TAX1BP1 from the glucocorticoid receptor-containing protein complex, and represses the co-activator function of TAX1BP1. 11718272_a_at TAX1BP1 Tax1 (human T-cell leukemia virus type I) binding protein 1 Cytoplasm other down 0.01 -0.76 1.17 ILMN_2374770 TAX1BP1 down 0.02 -0.45 1.17 TAX1BP1 20304918 TAX1BP1 and TNFAIP3 (A20) inhibit antiviral signalling by targeting TBK1/IKKi kinases and disrupting the TRAF3-TBK1-IKKi signalling complex. ILMN_1793118 TAX1BP1 down 0.00 -0.56 0.90 21765415 TAX1BP1 phosphorylation by CHUK is pivotal for the proinflammatory cytokine-dependent assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation. (Demonstrated in mouse) 11723206_at TCL1A T-cell leukemia/lymphoma 1A Nucleus other down 0.01 -0.67 0.46 ILMN_1788841 TCL1A down 0.00 -0.49 0.31 11754072_a_at TCL1A T-cell leukemia/lymphoma 1A Nucleus other down 0.01 -0.67 0.40 11754073_x_at TCL1A T-cell leukemia/lymphoma 1A Nucleus other down 0.01 -0.61 0.52 11725154_a_at TDRD9 tudor domain containing 9 Cytoplasm other down 0.00 -0.50 0.31 ILMN_2169490 TDRD9 down 0.01 -0.26 0.39 11743810_s_at TFAM transcription factor A, mitochondrial Cytoplasm transcription regulator down 0.03 -0.47 0.49 ILMN_1715661 TFAM down 0.01 -0.45 0.13 11736608_a_at TGM3 transglutaminase 3 (E polypeptide, protein-glutamine-gamma-glutamyltransferase)Cytoplasm enzyme down 0.01 -0.83 1.10 ILMN_1786847 TGM3 down 0.01 -0.50 1.16 11732857_a_at THAP1 THAP domain containing, apoptosis associated protein 1 Nucleus other down 0.02 -0.69 1.17 ILMN_1757272 THAP1 down 0.00 -0.46 0.84 11755219_a_at THBD thrombomodulin Plasma Membrane transmembrane receptor down 0.03 -0.96 1.11 ILMN_1759787 THBD down 0.04 -0.47 0.84 11753470_a_at TIA1 TIA1 cytotoxic granule-associated RNA binding protein Nucleus other down 0.04 -0.43 1.17 ILMN_1778691 TIA1 down 0.01 -0.43 0.57 11730229_a_at TIAL1 TIA1 cytotoxic granule-associated RNA binding protein-like 1 Nucleus transcription regulator down 0.02 -0.47 1.17 ILMN_2351309 TIAL1 down 0.00 -0.39 1.21 11737763_a_at TIAM2 T-cell lymphoma invasion and metastasis 2 Cytoplasm enzyme up 0.00 0.71 0.92 ILMN_2358560 TIAM2 up 0.01 0.30 1.16 11757359_x_at TMA7 translational machinery associated 7 homolog (S. cerevisiae) unknown other up 0.02 0.64 1.08 ILMN_1707783 TMA7 up 0.00 0.55 0.16 11731400_s_at TMCO1 transmembrane and coiled-coil domains 1 unknown other down 0.01 -0.89 1.17 ILMN_1793829 TMCO1 down 0.02 -0.58 0.34 11762892_at TMCO1 transmembrane and coiled-coil domains 1 unknown other down 0.04 -0.82 1.17 11725311_s_at TMED7 transmembrane emp24 protein transport domain containing 7 Cytoplasm transporter down 0.03 -0.65 1.17 ILMN_1672405 TMED7 down 0.05 -0.37 1.09 11725313_s_at TMED7 transmembrane emp24 protein transport domain containing 7 Cytoplasm transporter down 0.05 -0.55 1.10 11751628_a_at TMEM140 transmembrane protein 140 unknown other down 0.02 -0.80 1.09 ILMN_1736863 TMEM140 down 0.00 -0.60 1.22 11724275_s_at TMEM158 transmembrane protein 158 (gene/pseudogene) Plasma Membrane other up 0.00 1.18 0.90 ILMN_1792455 TMEM158 up 0.00 0.74 1.07 11751378_a_at TMEM161B transmembrane protein 161B unknown other down 0.02 -0.64 0.56 ILMN_1807580 TMEM161B down 0.02 -0.49 0.88 11758072_s_at TMEM161B transmembrane protein 161B unknown other down 0.04 -0.61 0.92 11720217_a_at TMEM176A transmembrane protein 176A unknown other down 0.00 -1.23 0.05 ILMN_1791511 TMEM176A down 0.00 -0.77 0.55 11719871_a_at TMEM176B transmembrane protein 176B unknown other down 0.00 -1.28 0.13 ILMN_2085012 TMEM176B down 0.00 -0.48 0.18 11739103_a_at TMEM33 transmembrane protein 33 Cytoplasm other down 0.03 -0.54 1.17 ILMN_1760620 TMEM33 down 0.01 -0.43 0.72 11739104_x_at TMEM33 transmembrane protein 33 Cytoplasm other down 0.00 -0.65 1.16 11756570_a_at TMEM50B transmembrane protein 50B Plasma Membrane other down 0.01 -0.76 1.17 ILMN_1757391 TMEM50B down 0.01 -0.48 0.20 11758779_at TMEM50B transmembrane protein 50B Plasma Membrane other down 0.04 -0.51 0.73 11727254_a_at TMEM51 transmembrane protein 51 unknown other up 0.00 0.90 1.12 ILMN_1674985 TMEM51 up 0.00 0.40 0.34 11724551_x_at TMEM55A transmembrane protein 55A unknown phosphatase down 0.00 -0.73 1.16 ILMN_1752117 TMEM55A down 0.00 -0.62 1.16 11721097_at TMX1 thioredoxin-related transmembrane protein 1 Cytoplasm enzyme down 0.00 -0.65 0.64 ILMN_1691181 TMX1 down 0.01 -0.58 0.75 11721098_x_at TMX1 thioredoxin-related transmembrane protein 1 Cytoplasm enzyme down 0.02 -0.72 1.17 11721730_at TMX3 thioredoxin-related transmembrane protein 3 Cytoplasm enzyme down 0.00 -0.67 0.97 ILMN_2047206 TMX3 down 0.00 -0.54 0.58 11721732_at TMX3 thioredoxin-related transmembrane protein 3 Cytoplasm enzyme down 0.00 -0.75 0.89 11738483_a_at TNFRSF13B tumor necrosis factor receptor superfamily, member 13B Plasma Membrane transmembrane receptor up 0.02 0.84 0.72 ILMN_1759075 TNFRSF13B up 0.00 0.58 0.61 TNFRSF13B 20676093 TNFRSF13B (TACI) triggers class-switch recombination (CSR) via the DNA-editing enzyme AID by activating NF-kappaB through a Toll-like receptor (TLR)-like MyD88-IRAK1-IRAK4-TRAF6-TAK1 pathway. 11738484_x_at TNFRSF13B tumor necrosis factor receptor superfamily, member 13B Plasma Membrane transmembrane receptor up 0.02 0.67 0.73 11751841_a_at TNFRSF17 tumor necrosis factor receptor superfamily, member 17 Plasma Membrane other up 0.00 0.99 0.14 ILMN_1768016 TNFRSF17 up 0.00 0.43 0.06 11723594_a_at TNK2 tyrosine kinase, non-receptor, 2 Cytoplasm kinase vemurafenib up 0.01 0.58 1.17 ILMN_1754708 TNK2 down 0.03 -0.38 1.04 ILMN_1669703 TNK2 updown 0.00 0.04 0.45 -0.35 0.85 0.41 11743578_x_at TOMM5 translocase of outer mitochondrial membrane 5 homolog (yeast) Cytoplasm other up 0.04 0.77 0.96 ILMN_1808661 TOMM5 up 0.02 0.50 0.25 11725032_a_at TPP1 tripeptidyl peptidase I Cytoplasm peptidase down 0.03 -0.59 1.16 ILMN_1729234 TPP1 down 0.05 -0.45 0.98 11752596_s_at TPP1 tripeptidyl peptidase I Cytoplasm peptidase down 0.00 -0.77 1.10 11752885_x_at TPP1 tripeptidyl peptidase I Cytoplasm peptidase down 0.01 -0.60 1.05 18849341 TRAFD1 deficiency reveals its negative regulatory role in the TLR and RIG-I-like helicases signalling pathway and was found to interact with TRIF, IPS-1, TRAF3 and TRAF6 in mice 11740997_a_at TRAFD1 TRAF-type zinc finger domain containing 1 unknown other up 0.04 0.40 0.13 ILMN_1758250 TRAFD1 up 0.00 0.45 0.08 TRAFD1 16221674 TRAFD1 is an interferon and LPS inducible gene acting as a negative regulator of Toll-like receptor signalling. 11736266_a_at TRAPPC8 trafficking protein particle complex 8 Cytoplasm transporter down 0.01 -0.51 1.11 ILMN_1796240 TRAPPC8 down 0.00 -0.36 1.22 11736267_at TRAPPC8 trafficking protein particle complex 8 Cytoplasm transporter down 0.04 -0.45 1.17 11745633_a_at TRAPPC8 trafficking protein particle complex 8 Cytoplasm transporter down 0.02 -0.53 0.94 11731742_a_at TRDMT1 tRNA aspartic acid methyltransferase 1 Nucleus enzyme down 0.00 -0.72 1.17 ILMN_1688104 TRDMT1 down 0.01 -0.31 1.17 11731743_a_at TRDMT1 tRNA aspartic acid methyltransferase 1 Nucleus enzyme down 0.04 -0.92 0.91 20797396 TREM1 is a superimmunoglobulin receptor present on neutrophils and monocytes, which plays an important role in the amplification of inflammation and its expression is inhibited by PGD(2) and PGJ(2) in macrophages. 11731744_a_at TRDMT1 tRNA aspartic acid methyltransferase 1 Nucleus enzyme down 0.03 -0.50 0.66 21393102 TREM1 is an activating receptor expressed on neutrophils and monocytes that amplifies inflammation induced by TLR4-signalling, specifically in the induction of TNFA production. 11746988_a_at TRDMT1 tRNA aspartic acid methyltransferase 1 Nucleus enzyme down 0.00 -0.67 0.58 21555403 TREM1 expression is upregulated following Pseudomonas aeruginosa infection in the cornea and the inhibition of TREM1 reduces the severity of corneal disease. TREM1 acts as an inflammatory amplifier in P. aeruginosa keratitis by modulating TLR signalling and Th1/Th2 responses. 11719862_a_at TREM1 triggering receptor expressed on myeloid cells 1 Plasma Membrane other down 0.01 -0.74 1.17 ILMN_1688231 TREM1 down 0.00 -0.51 0.93 TREM1 21690199 TREM1 expression is induced by vitamin D3 in human bronchial epithelial cells. Activation of TREM1 leads to the induction of human beta defensin 2 and TNF-alpha mRNA in the airway epithelium. 11746721_a_at TREM1 triggering receptor expressed on myeloid cells 1 Plasma Membrane other down 0.00 -0.94 1.16 22459945 TREM1 mediates endotoxin tolerance in monocytes through its ability to induce anti- or pro-inflammatory signals depending on its membrane-bound state. 11746560_a_at TREML1 triggering receptor expressed on myeloid cells-like 1 Plasma Membrane other up 0.00 0.81 0.90 ILMN_1690783 TREML1 up 0.05 0.31 0.78 23475790 TREM1 expression and shedding are regulated by CpG-mediated TLR9 activation in macrophages. 11722902_a_at TRMT13 tRNA methyltransferase 13 homolog (S. cerevisiae) unknown other down 0.00 -0.87 0.62 ILMN_1659786 TRMT13 down 0.01 -0.51 0.09 11745452_a_at TRMT13 tRNA methyltransferase 13 homolog (S. cerevisiae) unknown other down 0.01 -0.58 0.63 11722543_at TRPC1 transient receptor potential cation channel, subfamily C, member 1 Plasma Membrane ion channel down 0.00 -1.15 0.70 ILMN_1674380 TRPC1 down 0.03 -0.39 0.95 11755576_a_at TRPM6 transient receptor potential cation channel, subfamily M, member 6 Plasma Membrane kinase down 0.01 -0.77 1.16 ILMN_1814296 TRPM6 down 0.01 -0.53 0.15 11755284_s_at TSPAN13 tetraspanin 13 Plasma Membrane other down 0.03 -0.67 0.56 ILMN_1669881 TSPAN13 down 0.01 -0.61 0.06 11721184_at TSPAN33 tetraspanin 33 Plasma Membrane other up 0.00 0.55 1.14 ILMN_1749403 TSPAN33 up 0.00 0.51 1.13 11717082_a_at TSPAN9 tetraspanin 9 Plasma Membrane other up 0.00 0.60 1.12 ILMN_1729453 TSPAN9 up 0.00 0.39 0.79 11759347_x_at TXK TXK tyrosine kinase Cytoplasm kinase up 0.04 0.43 1.08 ILMN_1741143 TXK up 0.03 0.48 1.10 11731479_s_at TXNDC9 thioredoxin domain containing 9 unknown other down 0.04 -0.69 1.17 ILMN_1731137 TXNDC9 down 0.03 -0.42 0.63 11715650_a_at TXNRD1 thioredoxin reductase 1 Cytoplasm enzyme down 0.03 -0.53 1.17 ILMN_1717056 TXNRD1 down 0.00 -0.48 0.77 11739895_a_at USP1 ubiquitin specific peptidase 1 Cytoplasm peptidase down 0.01 -0.55 1.09 ILMN_1696975 USP1 down 0.01 -0.39 1.20 11717778_at USP15 ubiquitin specific peptidase 15 Cytoplasm peptidase down 0.02 -0.63 1.13 ILMN_1867588 USP15 down 0.00 -0.44 1.10 ILMN_1665557 USP15 down 0.02 -0.47 0.75 11739557_a_at VAMP5 vesicle-associated membrane protein 5 (myobrevin) Plasma Membrane transporter up 0.00 0.58 0.59 ILMN_1809467 VAMP5 up 0.00 0.53 0.73 11750328_s_at WAPAL wings apart-like homolog (Drosophila) Nucleus other down 0.01 -0.65 1.09 ILMN_1693668 WAPAL down 0.02 -0.45 1.14 11750329_x_at WAPAL wings apart-like homolog (Drosophila) Nucleus other down 0.00 -0.60 1.07 11726286_a_at WARS tryptophanyl-tRNA synthetase Cytoplasm enzyme up 0.00 0.92 0.44 ILMN_1727271 WARS updown 0.00 0.00 0.79 -0.50 0.68 0.14 11726287_a_at WARS tryptophanyl-tRNA synthetase Cytoplasm enzyme up 0.00 0.92 1.00 ILMN_2337655 WARS updown 0.00 0.01 0.83 -0.57 0.40 0.22 11747666_a_at WARS tryptophanyl-tRNA synthetase Cytoplasm enzyme up 0.00 0.90 0.08 11743605_s_at VBP1 von Hippel-Lindau binding protein 1 Cytoplasm other down 0.04 -0.62 1.12 ILMN_2223010 VBP1 down 0.02 -0.55 0.59 ILMN_1800612 VBP1 down 0.00 -0.58 0.51 11726292_s_at WDR44 WD repeat domain 44 Cytoplasm other down 0.02 -0.43 1.15 ILMN_2178618 WDR44 down 0.02 -0.32 1.11 11718760_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.00 -0.70 0.41 ILMN_1660549 WLS down 0.01 -0.30 0.06 11718761_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.00 -0.92 0.20 ILMN_2283325 WLS down 0.00 -0.93 0.08 11733513_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.00 -0.60 0.23 ILMN_2399769 WLS down 0.00 -0.48 0.89 11745018_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.00 -1.07 0.29 11729843_s_at VNN1 vanin 1 Plasma Membrane enzyme down 0.01 -0.91 1.17 ILMN_1674574 VNN1 down 0.00 -0.56 1.18 11729844_at VNN1 vanin 1 Plasma Membrane enzyme down 0.00 -0.88 1.17 11758233_s_at VNN1 vanin 1 Plasma Membrane enzyme down 0.01 -0.82 1.17 11732926_a_at VNN3 vanin 3 Extracellular Space enzyme down 0.01 -0.78 0.68 ILMN_2387680 VNN3 down 0.00 -0.47 1.14 11737877_a_at VNN3 vanin 3 Extracellular Space enzyme down 0.00 -0.86 0.68 ILMN_1804935 VNN3 down 0.00 -0.51 0.12 11746681_a_at VNN3 vanin 3 Extracellular Space enzyme down 0.02 -0.75 0.41 11763332_a_at VPS36 vacuolar protein sorting 36 homolog (S. cerevisiae) Cytoplasm other down 0.04 -0.50 1.16 ILMN_1802519 VPS36 down 0.03 -0.35 0.79 11739263_x_at VPS4B vacuolar protein sorting 4 homolog B (S. cerevisiae) Cytoplasm transporter down 0.03 -0.46 1.17 ILMN_1792587 VPS4B down 0.00 -0.34 0.82 11760162_at WSB1 WD repeat and SOCS box containing 1 unknown other down 0.01 -0.84 1.16 ILMN_1664802 WSB1 down 0.01 -0.48 1.21 11720038_at VTA1 Vps20-associated 1 homolog (S. cerevisiae) Cytoplasm other down 0.01 -0.51 1.17 ILMN_1813010 VTA1 down 0.00 -0.44 0.91 11751281_a_at VWCE von Willebrand factor C and EGF domains unknown other up 0.00 1.32 1.16 ILMN_1760315 VWCE up 0.00 0.66 1.14 11756497_a_at VWCE von Willebrand factor C and EGF domains unknown other up 0.00 1.30 1.14 11723140_at ZBTB11 zinc finger and BTB domain containing 11 Nucleus other down 0.01 -0.67 0.95 ILMN_1691395 ZBTB11 down 0.00 -0.49 0.45 11721520_at ZDHHC17 zinc finger, DHHC-type containing 17 Cytoplasm enzyme down 0.00 -0.73 1.02 ILMN_1697153 ZDHHC17 down 0.00 -0.64 0.54 11721521_at ZDHHC17 zinc finger, DHHC-type containing 17 Cytoplasm enzyme down 0.00 -0.70 1.00 11717075_a_at ZFAND6 zinc finger, AN1-type domain 6 unknown other down 0.02 -0.65 1.09 ILMN_2156953 ZFAND6 down 0.03 -0.45 1.17 11717077_x_at ZFAND6 zinc finger, AN1-type domain 6 unknown other down 0.04 -0.48 1.06 11754534_a_at ZFYVE16 zinc finger, FYVE domain containing 16 Nucleus transporter down 0.00 -0.78 1.17 ILMN_1651769 ZFYVE16 down 0.00 -0.64 0.95 11727886_a_at ZNF25 zinc finger protein 25 Nucleus other down 0.03 -0.46 0.84 ILMN_1808765 ZNF25 down 0.01 -0.36 1.20 11728481_a_at ZNF302 zinc finger protein 302 Nucleus other down 0.00 -1.02 0.53 ILMN_2307450 ZNF302 down 0.03 -0.63 0.30 11728482_a_at ZNF302 zinc finger protein 302 Nucleus other down 0.03 -0.83 0.49 11750396_x_at ZNF302 zinc finger protein 302 Nucleus other down 0.03 -0.78 0.71 11755529_s_at ZNF322 zinc finger protein 322 Cytoplasm other down 0.02 -0.57 1.17 ILMN_2171461 ZNF322 down 0.00 -0.53 1.21 11727704_a_at ZNF439 zinc finger protein 439 Nucleus other down 0.04 -0.73 0.09 ILMN_1792972 ZNF439 down 0.01 -0.49 0.52 11731362_a_at ZNF624 zinc finger protein 624 Nucleus other down 0.00 -0.79 1.11 ILMN_1670122 ZNF624 down 0.00 -0.46 0.57 11745146_a_at ZNF624 zinc finger protein 624 Nucleus other down 0.00 -0.88 1.17 11715211_s_at ZNF680 zinc finger protein 680 Nucleus other down 0.05 -0.91 0.46 ILMN_1730888 ZNF680 down 0.04 -0.37 0.87 11727200_s_at ZRANB2 zinc finger, RAN-binding domain containing 2 Nucleus transcription regulator down 0.04 -0.64 1.02 ILMN_1703015 ZRANB2 down 0.01 -0.40 0.76 11728652_x_at ZRANB2 zinc finger, RAN-binding domain containing 2 Nucleus transcription regulator down 0.01 -0.72 0.92 Page 81 of 111 Diabetes

Differentially regulated genes in T1D progressors (first sheet) were analyzed with DAVID pathway analysis tool. Pathways (BBID, BioCarta, KEGG, Panther, Reactome) with FDR <20% are reported.

Up-regulation Category Term Count % PValue Genes List Total Pop Hits Pop Total Fold Enrichment Bonferroni Benjamini FDR PANTHER_PATHWAY P05912:Dopamine receptor mediated signaling pathway 4 3.45 0.0185727 FRMD3, EPB41L3, PRKAR2B, CLIC3 20 87 2857 6.567816091954024 0.4907943020880374 0.4907943020880374 15.398020762998499

Down-regulation Category Term Count % PValue Genes List Total Pop Hits Pop Total Fold Enrichment Bonferroni Benjamini FDR BIOCARTA h_nthiPathway:NFkB activation by Nontypeable Hemophilus influenzae 5 1.50 0.0013950 MYD88, IL8, SMAD4, NR3C1, CHUK 32 24 1437 9.355468750000002 0.12907665990621053 0.12907665990621053 1.5346088998247742 KEGG_PATHWAY hsa00532:Chondroitin sulfate biosynthesis 4 1.20 0.0096480 CSGALNACT1, CSGALNACT2, CHST13, CHST15 105 22 5085 8.805194805194807 0.6315944201127621 0.6315944201127621 10.255667439655724 KEGG_PATHWAY hsa04610:Complement and coagulation cascades 6 1.80 0.0129656 C5AR1, THBD, C4B, CD46, SERPINA1, PLAUR 105 69 5085 4.211180124223603 0.739248243632284 0.4893614229538509 13.554521400904529 PANTHER_PATHWAY P04395:Vasopressin synthesis 3 0.90 0.0143613 PAM, SPCS3, PREPL 50 11 2857 15.583636363636364 0.6150799524554483 0.6150799524554483 13.748303106965675

Up- or down-regulation Category Term Count % PValue Genes List Total Pop Hits Pop Total Fold Enrichment Bonferroni Benjamini FDR BIOCARTA h_nthiPathway:NFkB activation by Nontypeable Hemophilus influenzae 6 1.19 0.0008040 MYD88, IL8, SMAD4, NR3C1, CHUK, MAP2K6 48 24 1437 7.484375000000001 0.0890807447768871 0.0890807447768871 0.9134364803351058 KEGG_PATHWAY hsa03010:Ribosome 10 1.99 0.0017220 RPS26, RPL36A, RPS3A, RPL9, RPL26, RPS15A, RPS27L, RSL24D1, RPS23, RPS24 164 87 5085 3.5639192598822538 0.19241925189338427 0.19241925189338427 1.9705111311904222 PANTHER_PATHWAY P05912:Dopamine receptor mediated signaling pathway 9 1.79 0.0023836 GNAZ, FRMD3, EPB41L3, PRKAR2B, STX3, GNAI3, CLIC3, CLIC4, FLNA 80 87 2857 3.694396551724138 0.17182258167086994 0.17182258167086994 2.4989720274932736 Diabetes Page 82 of 111

Differentially regulated genes in T1D progressors (first sheet) were analyzed through MSig database for enriched transcription factor binding sites on their promoters ( ±±±2 kb around the transcription start site). Motifs with p value < 0.05 are reported.

Enriched motif Motif sequence Transcription factor # Genes annotated to motif (K) # Overlapping input genes (k) k/K p value Genes Up-regulated genes STTTCRNTTT_V$IRF_Q6 STTTCRNTTT No match 188 7 0.0372 0.000956 MOV10 NT5C3 RBCK1 ALDH1A1 LGALS3BP PSIP1 VAMP5 V$ICSBP_Q6 RAARTGAAACTG IRF8 248 8 0.0323 0.001060 MOV10 NT5C3 RBCK1 ALDH1A1 SOCS1 PARP12 TNFRSF17 SP140 V$IRF7_01 TNSGAAWNCGAAANTNNN IRF7 252 6 0.0238 0.018400 MOV10 NT5C3 RBCK1 LGALS3BP SOCS1 PARP12

Down-regulated genes GCGSCMNTTT_UNKNOWN GCGSCMNTTT No match 69 5 0.0725 0.021200 STAG2 CDC14A ARID4A CEP135 BCLAF1 V$GATA1_03 ANGNDGATAANNGN GATA1 245 11 0.0449 0.026500 STAG2 FBXO11 ITSN2 MBNL1 PCDH9 ADM CREB5 CHMP2B TMEM161BPGGT1B RAB11A RYCACNNRNNRNCAG_UNKNOWN RYCACNNRNNRNCAG No match 76 5 0.0658 0.030600 FBXO11 ITSN2 LDB2 STAT3 CHST13 V$CHOP_01 NNRTGCAATMCCC DDIT3 238 11 0.0420 0.048900 FBXO11 MBNL1 PCDH9 ADM HIST1H2BDSLC38A2 JMJD1C SLC35A5 ZBTB11 HMGB1

Up- or down-regulated genes TMTCGCGANR_UNKNOWN TMTCGCGANR No match 160 12 0.0750 0.011400 DDX3X THAP1 CHUK WDR44 TMCO1 COX7B FGFR1OP2 MARCH7 RPS15A RPL26 CHURC1 ANKFY1

No match = Motif does not match any known transcription factor Page 83 of 111 Diabetes

Differentially expressed genes before seroconversion (FDR < 0.05) showing concordant changes in Affymetrix and Illumina arrays, and information regarding the innate immunity function of the genes (InnateDB)

AFFYMETRIX Case vs. control ILLUMINA Case vs. control InnateDB (www.innatedb.org) Innate Immunity Genes in human. P value for enrichment is 0.000114. Affymetrix ID Gene Symbol (IPA) Gene name (IPA) Location (IPA) Type (IPA) Drug (IPA) Change probeset FDR max FDR min SLR max SLR min Illumina ID Gene Symbol (IPA) Change probeFDR max FDR min SLR max SLR min Gene Symbol (human)Pubmed ID Annotation 11756406_x_at ADM adrenomedullin Extracellular Space other up 0.033 1.0831 ILMN_1708934 ADM updown 0.0089 0.0436 0.6765 -0.4954 11716710_a_at ADM adrenomedullin Extracellular Space other up 0.0497 1.1552 11754693_a_at AHI1 Abelson helper integration site 1 Cytoplasm other down 0.0343 -1.1419 ILMN_1791006 AHI1 down 0.0478 -0.1971 11729336_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase up 0 1.3086 ILMN_1701603 ALPL updown 0 0.011 1.4255 -0.2768 11748031_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase up 0 1.3119 11748032_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase up 0.0006 1.368 11729337_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase up 0.0009 1.2904 11750919_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase up 0.0028 1.544 11724283_a_at ANXA3 annexin A3 Cytoplasm enzyme updown 0.0036 0.0419 1.4408 -0.5676 ILMN_1694548 ANXA3 updown 0.013 0.0128 0.4852 -0.3626 11756334_x_at ANXA3 annexin A3 Cytoplasm enzyme up 0.0016 1.5299 11729871_a_at ASGR2 asialoglycoprotein receptor 2 Plasma Membrane transmembrane receptor up 0.0284 1.1679 ILMN_1694966 ASGR2 up 0.0053 0.7286 11759322_at BCL6 B-cell CLL/lymphoma 6 Nucleus transcription regulator up 0.0276 1.0112 ILMN_1737314 BCL6 up 0.0297 0.464 11755220_a_at C17orf97 chromosome 17 open reading frame 97 unknown other down 0.0387 -1.0877 ILMN_1707137 C17orf97 down 0.0098 -0.6564 11725888_at C19orf59 chromosome 19 open reading frame 59 unknown other up 0.0053 0.976 ILMN_1762713 C19orf59 updown 0.0017 0.0037 1.055 -0.368 11725889_at C19orf59 chromosome 19 open reading frame 59 unknown other up 0.0101 0.8855 11721099_at C3AR1 complement component 3a receptor 1 Plasma Membrane G-protein coupled receptor up 0.0175 1.0625 ILMN_1787529 C3AR1 up 0.0045 0.4812 11744719_x_at C4BPA complement component 4 binding protein, alpha Extracellular Space other up 0 2.9111 ILMN_1810752 C4BPA up 0.029 0.5613 C4BPA 21283780 C4BPA plays an inhibitory role in antimicrobial response by delaying the classical complement activation and attenuating the lectin pathway activation. The major inhibitory role of C4BPA is to facilitate the decay of C3 convertase. 11723949_a_at C4BPA complement component 4 binding protein, alpha Extracellular Space other up 0 2.5189 11755573_s_at C5orf4 chromosome 5 open reading frame 4 unknown other up 0.0007 1.4875 ILMN_1728742 C5orf4 up 0.0114 0.5506 11751501_a_at C5orf4 chromosome 5 open reading frame 4 unknown other up 0.0008 1.449 11748570_a_at C5orf4 chromosome 5 open reading frame 4 unknown other up 0.02 1.102 11716889_at C9orf123 chromosome 9 open reading frame 123 unknown other down 0.015 -1.0983 ILMN_1769409 C9orf123 down 0.0054 -0.6431 11742124_a_at CACNG6 calcium channel, voltage-dependent, gamma subunit 6 Plasma Membrane ion channel up 0.0289 1.032 ILMN_1779043 CACNG6 up 0.0118 0.6553 11731726_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase updown 0.0052 0.0074 1.1228 -1.1789 ILMN_1722158 CASP5 updown 0.0025 0.0159 0.4247 -0.2689 11731727_x_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase updown 0.0079 0.0292 1.2606 -0.675 11753343_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase updown 0.0064 0.0418 0.932 -0.542 11744286_s_at CBS cystathionine-beta-synthase Cytoplasm enzyme up 0.0224 1.256 ILMN_1804735 CBS up 0.0214 0.5413 11744660_s_at CCL4L1/CCL4L2 chemokine (C-C motif) ligand 4-like 1 Plasma Membrane other down 0.0494 -1.0329 ILMN_1716276 CCL4L1/CCL4L2 down 0.0445 -0.3133 11728039_s_at CCL8 chemokine (C-C motif) ligand 8 Extracellular Space cytokine up 0.008 0.4588 ILMN_1772964 CCL8 up 0.0007 0.6307 11756058_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other up 0.0185 0.9857 ILMN_1664330 CEACAM1 up 0.0067 0.4527 CEACAM1 18836450 CEACAM1 inhibits TLR2 induced pro-inflammatory immune responses by inducing PTPN6-(SHP-1)-mediated inhibition of the PI3K-NF-kappaB signal transduction pathway in pulmonary epithelial cells. 11751094_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other up 0.0186 1.13 ILMN_1716815 CEACAM1 up 0.0153 0.7294 11751217_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other up 0.0354 0.9541 11751095_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other up 0.0419 0.852 11723565_a_at CENPA centromere protein A Nucleus other down 0.0414 -0.9121 ILMN_1801257 CENPA down 0.0264 -0.425 11758261_s_at CEP55 centrosomal protein 55kDa Cytoplasm other down 0.0155 -0.8329 ILMN_1747016 CEP55 down 0 -0.6669 11720247_a_at CEP55 centrosomal protein 55kDa Cytoplasm other down 0.016 -1.2083 11727473_at CLC Charcot-Leyden crystal protein Cytoplasm enzyme up 0.0455 0.9848 ILMN_1654875 CLC up 0.0011 1.0952 11748403_x_at CNN2 calponin 2 Cytoplasm other up 0.0101 1.0779 ILMN_1770290 CNN2 up 0.0495 0.4174 11723416_x_at CNN2 calponin 2 Cytoplasm other up 0.0223 0.9302 11723414_a_at CNN2 calponin 2 Cytoplasm other up 0.0421 0.8495 11753841_x_at COMMD6 COMM domain containing 6 unknown other down 0.0057 -1.1631 ILMN_1777378 COMMD6 down 0.0019 -0.8383 11756875_x_at COMMD6 COMM domain containing 6 unknown other down 0.0067 -1.2137 11733495_a_at COMMD6 COMM domain containing 6 unknown other down 0.0103 -1.0989 11733496_x_at COMMD6 COMM domain containing 6 unknown other down 0.0167 -1.0294 11715694_at COX7B cytochrome c oxidase subunit VIIb Cytoplasm enzyme down 0.0056 -1.2678 ILMN_1794223 COX7B down 0.0002 -0.9838 11715695_x_at COX7B cytochrome c oxidase subunit VIIb Cytoplasm enzyme down 0.0081 -1.2494 11733803_x_at CPPED1 calcineurin-like phosphoesterase domain containing 1 unknown enzyme up 0.0367 1.0318 ILMN_1662865 CPPED1 up 0.0402 0.3933 11762865_a_at CREB5 cAMP responsive element binding protein 5 Nucleus transcription regulator up 0.0284 0.9864 ILMN_1731714 CREB5 up 0.0067 0.622 11750879_a_at CREB5 cAMP responsive element binding protein 5 Nucleus transcription regulator up 0.0313 0.9499 11748448_a_at CTTN cortactin Plasma Membrane other up 0.0255 1.09 ILMN_1744912 CTTN up 0.0134 0.5844 11733297_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.0061 -1.2068 ILMN_1736190 CYP4F3 down 0.0079 -0.7145 11716580_s_at CYSTM1 cysteine-rich transmembrane module containing 1 unknown other up 0.0169 1.0802 ILMN_1761566 CYSTM1 updown 0.0008 0.0047 0.9446 -0.2356 11716579_a_at CYSTM1 cysteine-rich transmembrane module containing 1 unknown other up 0.0195 1.1097 11718039_at DCAF12 DDB1 and CUL4 associated factor 12 Cytoplasm other up 0.0497 0.9613 ILMN_1786328 DCAF12 updown 0.0113 0.0414 0.604 -0.4545 11721438_s_at DEFA1 (includes others) defensin, alpha 1 Cytoplasm other up 0.0009 1.6995 ILMN_1679357 DEFA1 (includes others) updown 0.0004 0.0256 1.2318 -0.0658 ILMN_1725661 DEFA1 (includes others) updown 0.0024 0.0105 0.7138 -0.466 11725531_a_at DSC2 desmocollin 2 Plasma Membrane other up 0.0034 1.1286 ILMN_1782125 DSC2 up 0.0053 0.6795 11737096_a_at DSC2 desmocollin 2 Plasma Membrane other up 0.0077 1.0254 11757702_s_at DSC2 desmocollin 2 Plasma Membrane other up 0.0174 0.9113 11758499_s_at DTL denticleless E3 ubiquitin protein ligase homolog (Drosophila) Nucleus other down 0.0294 -0.9371 ILMN_1745251 DTL down 0.0442 -0.3987 11745836_x_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other up 0.0064 1.2095 ILMN_1810420 DYSF updown 0 0.0159 1.3796 -0.3604 11719223_a_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other up 0.0075 1.1719 11747936_a_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other up 0.0078 1.1165 11750862_a_at EMR3 egf-like module containing, mucin-like, hormone receptor-like 3 Plasma Membrane G-protein coupled receptor up 0.0307 1.0897 ILMN_1755873 EMR3 up 0.0263 0.5662 11725009_a_at EPB42 erythrocyte membrane protein band 4.2 Plasma Membrane transporter up 0.0036 1.4824 ILMN_1814397 EPB42 up 0.0003 0.9135 11741344_x_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0.0283 1.1064 ILMN_1671686 EPB49 up 0.0052 0.6201 11747661_x_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0.0422 0.9962 11747660_a_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0.0486 0.9409 11731181_a_at EPSTI1 epithelial stromal interaction 1 (breast) unknown other down 0.0194 -1.3186 ILMN_1688566 EPSTI1 updown 0.0154 0.0005 0.642 -1.022 11722573_a_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase down 0 -1.8009 ILMN_1743145 ERAP2 down 0 -1.051 11755895_a_at FAM129A family with sequence similarity 129, member A Cytoplasm other up 0.0316 0.9773 ILMN_1810725 FAM129A updown 0.0009 0.0457 0.8601 -0.3343 ILMN_1667966 FAM129A up 0.0024 0.5722 11739340_at FAM46C family with sequence similarity 46, member C Extracellular Space other up 0.0399 0.8777 ILMN_1713266 FAM46C up 0.017 0.7007 11744140_a_at FOLR3 folate receptor 3 (gamma) Extracellular Space other up 0.0044 1.0044 ILMN_1730454 FOLR3 updown 0.0007 0.0165 0.9121 -0.1887 11744141_x_at FOLR3 folate receptor 3 (gamma) Extracellular Space other up 0.0102 0.9414 11733439_a_at GBP5 guanylate binding protein 5 Plasma Membrane enzyme down 0.0414 -0.8959 ILMN_1779798 GBP5 down 0.0045 -0.6844 11724167_s_at GLT25D2 glycosyltransferase 25 domain containing 2 unknown other down 0.0242 -0.8592 ILMN_1736742 GLT25D2 down 0.0054 -0.5523 11724166_a_at GLT25D2 glycosyltransferase 25 domain containing 2 unknown other down 0.0293 -1.0964 11720202_at GMPR guanosine monophosphate reductase Cytoplasm enzyme up 0.0366 1.0272 ILMN_1729487 GMPR up 0.0028 0.5883 11763755_a_at GNLY granulysin Cytoplasm other down 0.0467 -0.6598 ILMN_1708779 GNLY down 0.0026 -0.7522 11737911_a_at GPR84 G protein-coupled receptor 84 Plasma Membrane G-protein coupled receptor up 0.0174 0.783 ILMN_1785345 GPR84 updown 0.0455 0.0446 0.2865 -0.1459 11725439_at HBD hemoglobin, delta Cytoplasm transporter up 0.0079 1.3343 ILMN_1815527 HBD updown 0.013 0.0092 0.63 -0.594 11725438_a_at HBD hemoglobin, delta Cytoplasm transporter up 0.0101 1.2355 11755374_a_at HERC5 HECT and RLD domain containing E3 ubiquitin protein ligase 5 Cytoplasm enzyme updown 0.0084 0.0137 1.2462 -1.2661 ILMN_1729749 HERC5 updown 0.01 0.0078 0.7281 -0.4577 HERC5 20308324 HERC5 positively regulates the innate antiviral responses by sustaining IRF3 activation via a novel post-translational modification, ISGylation. 11757222_at HINT1 histidine triad nucleotide binding protein 1 Nucleus enzyme down 0.0167 -1.2042 ILMN_1807710 HINT1 down 0 -1.0428 11726246_x_at HIST1H4A (includes others)histone cluster 1, H4a Nucleus other down 0.0423 -0.7575 ILMN_1698511 HIST1H4A (includes others)down 0.0231 -0.6004 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other up 0 1.6141 ILMN_1721113 HLA-C up 0.0006 1.1168 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor down 0 -5.4744 ILMN_1749070 HLA-DPB1 down 0.0227 -0.43 11760878_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor down 0.0041 -1.5095 11758089_s_at HMMR hyaluronan-mediated motility receptor (RHAMM) Plasma Membrane other down 0.0166 -1.2705 ILMN_1781942 HMMR down 0.0136 -0.4886 11724387_at HOXB2 homeobox B2 Nucleus transcription regulator down 0.0461 -0.9546 ILMN_1810274 HOXB2 down 0.0044 -0.5639 11715893_s_at IFI27 interferon, alpha-inducible protein 27 Cytoplasm other down 0 -2.3131 ILMN_1661581 IFI27 down 0 -1.2043 IFI27 20939681 IFI27 is a mitochondrial protein and its expression sensitizes cells to apoptotic stimuli via mitochondrial membrane destabilization. 11757480_x_at IFI27 interferon, alpha-inducible protein 27 Cytoplasm other down 0 -2.5554 11748003_a_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0217 0 0.8618 -1.6969 ILMN_1760062 IFI44 updown 0.0006 0 0.7346 -1.3958 11760254_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0079 0.0027 1.0596 -1.1562 11719886_a_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0496 0.0035 0.7283 -1.4978 11760252_at IFI44 interferon-induced protein 44 Cytoplasm other down 0.0007 -1.6058 11760253_x_at IFI44 interferon-induced protein 44 Cytoplasm other down 0.0024 -1.5596 11746088_a_at IFI44 interferon-induced protein 44 Cytoplasm other down 0.0196 -1.2524 11723236_at IFI44L interferon-induced protein 44-like unknown other updown 0.0068 0 0.9057 -2.1565 ILMN_1723912 IFI44L updown 0.0008 0 1.2214 -1.1906 11723234_at IFI44L interferon-induced protein 44-like unknown other updown 0.0024 0 1.4402 -1.9572 ILMN_1835092 IFI44L updown 0.0191 0.0081 0.3157 -0.6852 11723235_a_at IFI44L interferon-induced protein 44-like unknown other updown 0.0052 0.0004 1.2903 -1.8107 22065572 IFIT2 expression imparts anti-viral immunity to restrict West Nile virus infection and control viral pathogenesis. (Demonstrated in mice) 11721873_at IFIT2 interferon-induced protein with tetratricopeptide repeats 2 Cytoplasm other updown 0.0053 0.0352 1.2965 -1.0203 ILMN_1739428 IFIT2 updown 0.0014 0.0028 0.9445 -0.7592 IFIT2 19108715 IFIT2 belongs to type 1 interferon response genes and is highly induced after stimulation with LPS and selectively affects LPS induced protein expression by regulation at different post-transcriptional levels. 11731407_x_at IFIT3 interferon-induced protein with tetratricopeptide repeats 3 Cytoplasm other up 0.0077 1.1664 ILMN_1683865 IFIT3 up 0.0367 0.2545 IFIT3 21813773 IFIT3 triggers host antiviral responses by bridging TBK1 to MAVS, and IFIT3 plays an important role in the activation of IRF3. 11715239_x_at IFITM3 interferon induced transmembrane protein 3 Plasma Membrane other up 0.0125 0.9131 ILMN_1805750 IFITM3 updown 0 0 1.3853 -0.65 IFITM3 20601941 IFITM3 is post-translationally regulated by S-palmitoylation on membrane-proximal cysteines, which controls its clustering in membrane compartments and its antiviral activity against influenza virus. 11757763_s_at IGF2BP2 insulin-like growth factor 2 mRNA binding protein 2 Cytoplasm translation regulator up 0.0224 1.1153 ILMN_1702447 IGF2BP2 up 0.0015 0.8123 20064371 IFITM3 is an antiviral restriction factor that mediates cellular resistance to influenza A H1N1 virus, West Nile virus, and Dengue virus. 11749598_a_at IL18RAP interleukin 18 receptor accessory protein Plasma Membrane transmembrane receptor down 0.0193 -1.2093 ILMN_1721762 IL18RAP down 0.0037 -0.5118 18332133 IRF5 is activated by both TBK1 and MYD88 to form a homodimer that binds to and activates transcription of type I interferon and inflammatory cytokine genes. 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator up 0.0007 1.7251 ILMN_1670576 IRF5 up 0.0099 0.6453 IRF5 12600985 IRF5 can act as both an activator and a repressor of interferon (IFN) gene induction dependent on the IRF-interacting partner, and may be a part of the regulatory network that ensures timely expression of the immediate early inflammatory genes. 11719293_s_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other down 0.0264 -0.878 ILMN_1665107 ITGB1BP1 down 0.0136 -0.4482 22412986 Phosphorylation of IRF5 at ser451 and ser462 is the primary trigger of IRF5 function in nuclear accumulation, transcription and apoptosis. 11719292_a_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other down 0.0311 -0.7945 11720780_a_at KIAA1324 KIAA1324 Plasma Membrane other up 0.001 1.6057 ILMN_1771482 KIAA1324 up 0.0011 1.5675 11742216_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0294 -0.5566 ILMN_1799134 KLRD1 down 0.0048 -0.3185 11753534_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0377 -0.6094 11745699_a_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor down 0.0009 -1.2875 ILMN_1685521 KLRF1 down 0.0184 -0.4666 11740668_a_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor down 0.0399 -1.0736 11740669_x_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor down 0.0409 -0.9915 11753219_a_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor down 0.0494 -1.0346 11723952_at KRT1 keratin 1 Cytoplasm other up 0.001 1.3237 ILMN_1735712 KRT1 up 0.0004 0.86 11745488_s_at LILRB3 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains),Plasma member Membrane 3 transmembrane receptor up 0.0495 1.0673 ILMN_1784884 LILRB3 up 0.0122 0.7312 11751459_x_at LRG1 leucine-rich alpha-2-glycoprotein 1 Extracellular Space other up 0.0185 1.3207 ILMN_1805228 LRG1 up 0.0049 0.8396 11725368_at LRG1 leucine-rich alpha-2-glycoprotein 1 Extracellular Space other up 0.0466 1.1522 11757798_s_at MAFB v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) Nucleus other up 0.0422 0.9734 ILMN_1764709 MAFB up 0.0089 0.6611 MAFB 20581830 MAFB binds to IRF3, impairing the recruitment of co-activators to IRF3 and antagonizing antiviral responses. 11721630_at MAFB v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) Nucleus other up 0.0493 1.0082 11735581_a_at MBNL3 muscleblind-like splicing regulator 3 Nucleus other up 0.0224 0.9967 ILMN_1726088 MBNL3 updown 0.001 0.0475 0.9111 -0.2292 11763780_a_at MBNL3 muscleblind-like splicing regulator 3 Nucleus other up 0.0285 0.9596 11734952_a_at MBNL3 muscleblind-like splicing regulator 3 Nucleus other up 0.0302 1.0657 21873432 MMP9 and NEU1 cross-talk in alliance with TLR4 on the cell surface is a novel membrane sialidase-controlling mechanism that depends on ligand binding to its Toll-like receptor (TLR) to induce NEU1 activity, to influence receptor desialylation and subseque 11763736_a_at MBNL3 muscleblind-like splicing regulator 3 Nucleus other up 0.0444 1.1203 22496659 MMP9 inhibits influenza virus pathogenesis by mediating neutrophil migration to the respiratory tract. (Demonstrated in mice) 11719657_a_at MMP9 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)Extracellular Space peptidase up 0.0125 1.1517 ILMN_1796316 MMP9 updown 0.0012 0.0204 0.6868 -0.2642 MMP9 22860023 MMP9 cleaves the pulmonary collectin SFTPD (SP-D) leading to loss of its innate immune functions. (Demonstrated in mouse) 11716167_a_at MX1 myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse)Nucleus enzyme up 0.0087 1.4689 ILMN_1662358 MX1 updown 0.0024 0.0477 0.9337 -0.4284 MX1 18062906 MX1 is an interferon-induced member of the dynamin superfamily of large GTPases, which inhibit a wide range of viruses by blocking an early stage of the replication cycle. 11754928_x_at MYOF myoferlin Nucleus other up 0.0447 0.9564 ILMN_1810289 MYOF up 0.029 0.5677 22531919 MX1 expression is upregulated by alpha-defensins in gigival epithelial cell. 11749795_a_at NFIX nuclear factor I/X (CCAAT-binding transcription factor) Nucleus transcription regulator up 0.001 1.2769 ILMN_1694325 NFIX up 0.0177 0.7576 20538602 MX1 GTPase is a key mediator of cell-autonomous innate immunity against a broad range of viruses such as influenza and bunyaviruses. 11750902_x_at NFIX nuclear factor I/X (CCAAT-binding transcription factor) Nucleus transcription regulator up 0.0196 1.2174 11761655_at NPCDR1 nasopharyngeal carcinoma, down-regulated 1 unknown other up 0.0226 1.1716 ILMN_1780774 NPCDR1 up 0.05 0.3912 11724497_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0.0077 1.223 ILMN_1733581 NPRL3 up 0.0015 0.9058 11753912_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0.0076 1.1417 11748257_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0.0079 1.2912 11763176_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0.0101 1.2195 11724255_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme up 0.0168 1.1138 ILMN_1658247 OAS1 updown 0.001 0.0008 0.6911 -0.4712 OAS1 23319625 OAS1 is a cytoplasmic dsRNA sensor. 11740891_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme up 0.0293 0.9985 ILMN_1675640 OAS1 updown 0.002 0.0002 1.0031 -0.7556 21190483 OAS1 is a pathogen recognition receptor for the viral pathogen-associated molecular pattern, double-stranded RNA. Upon recognition of dsRNA, the OAS1 activates RNASEL to cleave ssRNA. The OAS/RNASEL pathway triggers the RIG-I pathway and induce IFNB produ 11723698_a_at OAS3 2-5-oligoadenylate synthetase 3, 100kDa Cytoplasm enzyme updown 0.0083 0.0051 1.2329 -1.274 ILMN_1745397 OAS3 updown 0.0027 0.0005 0.6614 -0.7563 OAS3 21190483 OAS3 is a pathogen recognition receptor for the viral pathogen-associated molecular pattern, double-stranded RNA. Upon recognition of dsRNA, the OAS3 activates RNASEL to cleave ssRNA. The OAS/RNASEL pathway triggers the RIG-I pathway and induce IFNB produ 11723699_s_at OAS3 2-5-oligoadenylate synthetase 3, 100kDa Cytoplasm enzyme updown 0.0185 0.0324 1.327 -0.9754 11736090_a_at OLIG2 oligodendrocyte lineage transcription factor 2 Nucleus transcription regulator up 0.0008 1.4158 ILMN_1727567 OLIG2 up 0.0005 0.9608 11736206_a_at OSBP2 oxysterol binding protein 2 Cytoplasm other up 0.0078 1.4157 ILMN_1781966 OSBP2 up 0.0053 0.7004 11750705_a_at OSBP2 oxysterol binding protein 2 Cytoplasm other up 0.0113 1.2107 11736205_a_at OSBP2 oxysterol binding protein 2 Cytoplasm other up 0.0232 1.1939 11740554_a_at PHOSPHO1 phosphatase, orphan 1 Extracellular Space enzyme up 0.022 1.0431 ILMN_1688240 PHOSPHO1 up 0.0498 0.496 11740244_a_at PHOSPHO1 phosphatase, orphan 1 Extracellular Space enzyme up 0.0239 1.0671 11721650_at PI3 peptidase inhibitor 3, skin-derived Extracellular Space other updown 0.0053 0.016 1.1827 -1.1363 ILMN_1693192 PI3 updown 0.0006 0 0.9369 -1.224 11715585_a_at PMP22 peripheral myelin protein 22 Plasma Membrane other up 0.0088 1.1726 ILMN_1785646 PMP22 up 0.0014 0.6886 11732808_a_at PROK2 prokineticin 2 Extracellular Space other up 0.0197 1.0085 ILMN_1775257 PROK2 up 0.014 0.4601 11718766_at PRSS23 protease, serine, 23 Extracellular Space peptidase down 0.0298 -1.0203 ILMN_1797776 PRSS23 down 0.0086 -0.5816 11731941_at PRSS33 protease, serine, 33 Extracellular Space peptidase up 0 1.983 ILMN_1736831 PRSS33 up 0.001 1.0798 11736667_a_at PTER phosphotriesterase related unknown enzyme down 0.0052 -1.5251 ILMN_1795336 PTER down 0.0354 -0.5041 11757833_a_at RAB31 RAB31, member RAS oncogene family Cytoplasm enzyme up 0.0118 1.1071 ILMN_1660691 RAB31 up 0.0279 0.4793 11716019_at RAB31 RAB31, member RAS oncogene family Cytoplasm enzyme up 0.0215 1.0834 11725237_a_at RBPMS2 RNA binding protein with multiple splicing 2 unknown other up 0.0025 1.2897 ILMN_1808238 RBPMS2 up 0.0008 0.7158 11739797_a_at RFX2 regulatory factor X, 2 (influences HLA class II expression) Nucleus transcription regulator up 0.0101 1.36 ILMN_1692159 RFX2 up 0.0016 0.8489 11755653_a_at RFX2 regulatory factor X, 2 (influences HLA class II expression) Nucleus transcription regulator up 0.0163 1.3223 11755743_a_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme up 0.0085 1.1517 ILMN_1730628 RNASE2 up 0.0025 0.7736 11729772_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme up 0.0275 1.0938 11720349_at ROPN1L rhophilin associated tail protein 1-like Cytoplasm kinase up 0.0168 1.108 ILMN_1696466 ROPN1L up 0.0289 0.4538 11757329_s_at RPL26 ribosomal protein L26 Cytoplasm other down 0.0413 -0.8105 ILMN_1731546 RPL26 updown 0.0153 0.0007 0.1976 -0.7511 11744350_a_at RPS27L ribosomal protein S27-like Nucleus other down 0.025 -1.0996 ILMN_1712678 RPS27L down 0.0002 -0.83 11754793_a_at RRP12 ribosomal RNA processing 12 homolog (S. cerevisiae) Nucleus other up 0.0283 0.9784 ILMN_1767253 RRP12 up 0.006 0.6258 11739217_a_at RSAD2 radical S-adenosyl methionine domain containing 2 Cytoplasm enzyme updown 0 0 1.5265 -2.3694 ILMN_1657871 RSAD2 updown 0.001 0 1.0826 -1.3622 RSAD2 20308629 RSAD2 (viperin) is an antiviral protein whose expression is highly upregulated during viral infections via IFN-dependent and/or IFN-independent pathways and an IRF1 mediated type I IFN independent mechanism of enhanced RSAD2 expression provides a redundan 11739216_x_at RSAD2 radical S-adenosyl methionine domain containing 2 Cytoplasm enzyme updown 0.002 0.0008 1.4061 -1.7188 11745760_x_at RSL24D1 ribosomal L24 domain containing 1 Nucleus other down 0.0033 -1.3171 ILMN_1803489 RSL24D1 down 0.0014 -0.7353 11724117_x_at SAMD9L sterile alpha motif domain containing 9-like Extracellular Space other down 0.0156 -1.1456 ILMN_1748256 SAMD9L down 0.0438 -0.4379 11755997_a_at SAMD9L sterile alpha motif domain containing 9-like Extracellular Space other down 0.0333 -0.9547 11757358_s_at SCOC short coiled-coil protein Cytoplasm other down 0.0359 -0.8973 ILMN_1768050 SCOC down 0.0011 -0.8622 11751213_s_at SCOC short coiled-coil protein Cytoplasm other down 0.0446 -1.0056 11717754_a_at SEC14L1 SEC14-like 1 (S. cerevisiae) Cytoplasm transporter up 0.0154 1.0718 ILMN_1732575 SEC14L1 up 0.0027 0.8252 Diabetes Page 84 of 111

11716401_a_at SELENBP1 selenium binding protein 1 Cytoplasm other up 0.0053 1.354 ILMN_1680652 SELENBP1 up 0.0026 0.6667 11730128_a_at SETD9 SET domain containing 9 unknown other down 0.029 -1.0448 ILMN_1757636 SETD9 down 0.0391 -0.5088 11732801_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other up 0 1.2469 ILMN_1675424 SIRPB1 up 0.0027 0.6425 11732800_a_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other up 0 1.36 11752660_a_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other up 0 1.26 11724454_at SLC22A4 solute carrier family 22 (organic cation/ergothioneine transporter), member 4 Plasma Membrane transporter up 0.0239 1.2875 ILMN_1685057 SLC22A4 up 0.0311 0.7008 11717162_a_at SLC29A1 solute carrier family 29 (nucleoside transporters), member 1 Plasma Membrane transporter up 0.0249 1.2777 ILMN_1723971 SLC29A1 up 0.0014 0.9342 11758430_s_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) up 0.002 1.588 ILMN_1772809 SLC4A1 updown 0.0051 0.0298 0.632 -0.2046 11726491_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) up 0.0023 1.6529 11726490_a_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) up 0.0034 1.5374 11730162_s_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0.0079 1.1634 ILMN_1806349 SLC6A8 up 0.0283 0.6331 11716741_x_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0.0167 1.0793 11716740_a_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0.0493 1.1775 11731064_a_at SMOX spermine oxidase Cytoplasm enzyme up 0.0293 1.1535 ILMN_1775380 SMOX updown 0.0052 0.0246 0.7801 0.1159 11731446_s_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0068 1.4315 ILMN_1701933 SNCA updown 0.0009 0.0171 0.73 -0.2626 SNCA 21747756 SNCA acts as a danger-associated molecular pattern that activates the expression of TLRs to initiate the proinflammatory pathway and microglial activation. 11731448_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0075 1.3301 ILMN_1766165 SNCA updown 0.0077 0.0232 0.3304 -0.2646 11731447_x_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0399 1.0854 11753731_x_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0445 1.0131 11754090_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0447 0.9504 11739782_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.046 1.0585 11727007_at SORT1 sortilin 1 Plasma Membrane transmembrane receptor up 0.0087 1.2639 ILMN_1707077 SORT1 up 0.0027 0.784 11746408_a_at SORT1 sortilin 1 Plasma Membrane transmembrane receptor up 0.0404 1.0557 11720598_x_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.0144 -1.2455 ILMN_1736054 SUB1 down 0.0022 -0.8325 11736608_a_at TGM3 transglutaminase 3 (E polypeptide, protein-glutamine-gamma-glutamyltransferase)Cytoplasm enzyme up 0.0278 1.1153 ILMN_1786847 TGM3 up 0.0053 0.4859 11722392_a_at TMEM126B transmembrane protein 126B unknown other down 0.021 -1.2255 ILMN_1766851 TMEM126B down 0.0055 -0.6405 11724275_s_at TMEM158 transmembrane protein 158 (gene/pseudogene) Plasma Membrane other up 0.0462 0.8943 ILMN_1792455 TMEM158 updown 0.0051 0.0277 0.6125 -0.2012 11745268_a_at TNS1 tensin 1 Plasma Membrane other up 0 1.5162 ILMN_1807919 TNS1 up 0.0004 0.9994 11716559_x_at TNS1 tensin 1 Plasma Membrane other up 0 1.6528 11716556_a_at TNS1 tensin 1 Plasma Membrane other up 0.0009 1.5131 11716558_at TNS1 tensin 1 Plasma Membrane other up 0.0009 1.3944 11716557_a_at TNS1 tensin 1 Plasma Membrane other up 0.0125 1.183 11731997_at TRIM58 tripartite motif containing 58 unknown other up 0.0029 1.5575 ILMN_1705458 TRIM58 up 0.0067 0.3883 TRIM58 23438823 TRIM58 was identified in a systematic screen for positive regulators of innate immune responses. 11731996_at TRIM58 tripartite motif containing 58 unknown other up 0.0158 1.0403 11743175_at TSHZ3 teashirt zinc finger homeobox 3 Nucleus transcription regulator up 0.0347 1.0202 ILMN_1743933 TSHZ3 up 0.0227 0.529 11742208_a_at VCAN versican Extracellular Space other up 0.0198 1.1312 ILMN_1687301 VCAN up 0.0128 0.5954 11748311_s_at VCAN versican Extracellular Space other up 0.0201 1.1487 11748164_a_at VCAN versican Extracellular Space other up 0.0247 1.1011 11729842_at VNN1 vanin 1 Plasma Membrane enzyme up 0.042 1.2164 ILMN_1712365 VNN1 up 0.0312 0.7207 11756497_a_at VWCE von Willebrand factor C and EGF domains unknown other up 0.012 1.3714 ILMN_1760315 VWCE up 0.0013 0.8732 11751281_a_at VWCE von Willebrand factor C and EGF domains unknown other up 0.0257 1.0384 11749370_x_at XAF1 XIAP associated factor 1 Nucleus other down 0.0384 -1.0816 ILMN_1742618 XAF1 updown 0.0403 0.0128 0.4592 -0.6855 11747631_x_at XAF1 XIAP associated factor 1 Nucleus other down 0.0392 -1.0372 Page 85 of 111 Diabetes

Differentially expressed genes at seroconversion (FDR < 0.05) showing concordant changes in Affymetrix and Illumina arrays, and information regarding the innate immunity function of the genes (InnateDB)

AFFYMETRIX Case vs. control ILLUMINA Case vs. control InnateDB (www.innatedb.org) Innate Immunity Genes in human. P value for enrichment is 0.056166. Affymetrix ID Gene Symbol (IPA) Gene name (IPA) Location (IPA) Type (IPA) Drug (IPA) Change probeset FDR max FDR min SLR max SLR min Illumina ID Gene Symbol (IPA) Change probeFDR max FDR min SLR max SLR min Gene Symbol (human)Pubmed ID Annotation 11729336_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase up 0.0244 0.6915 ILMN_1701603 ALPL up 0 0.6973 11748032_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase up 0.0274 0.619 11748031_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase up 0.0276 0.6319 11750919_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase up 0.0427 0.6052 11726243_a_at ANKDD1A ankyrin repeat and death domain containing 1A unknown other down 0.047 -0.6024 ILMN_1813139 ANKDD1A down 0.0002 -0.5029 11729344_at BPI bactericidal/permeability-increasing protein Plasma Membrane transporter up 0.0029 1.097 ILMN_1766736 BPI up 0.0236 0.2797 11721099_at C3AR1 complement component 3a receptor 1 Plasma Membrane G-protein coupled receptor up 0.0139 0.529 ILMN_1787529 C3AR1 up 0.0049 0.3309 11744719_x_at C4BPA complement component 4 binding protein, alpha Extracellular Space other up 0 0.3438 ILMN_1810752 C4BPA up 0.0155 0.1127 C4BPA 21283780 C4BPA plays an inhibitory role in antimicrobial response by delaying the classical complement activation and attenuating the lectin pathway activation. The major inhibitory role of C4BPA is to facilitate the decay of C3 convertase. 11723949_a_at C4BPA complement component 4 binding protein, alpha Extracellular Space other up 0.0023 -0.0136 11758685_s_at CEACAM8 carcinoembryonic antigen-related cell adhesion molecule 8 Plasma Membrane other up 0 1.2293 ILMN_1806056 CEACAM8 up 0.0357 0.2293 11750177_x_at CEACAM8 carcinoembryonic antigen-related cell adhesion molecule 8 Plasma Membrane other up 0.0019 0.8462 11734956_a_at CNTNAP2 contactin associated protein-like 2 Plasma Membrane other down 0.0238 -0.8388 ILMN_1690223 CNTNAP2 down 0.0003 -0.4956 11727284_at CUX2 cut-like homeobox 2 Nucleus transcription regulator down 0.0085 -0.4157 ILMN_1669876 CUX2 down 0.0455 -0.2476 11721438_s_at DEFA1 (includes others) defensin, alpha 1 Cytoplasm other up 0 1.1126 ILMN_1679357 DEFA1 (includes others) up 0 1.4297 ILMN_1725661 DEFA1 (includes others) up 0 0.765 ILMN_1693262 DEFA1 (includes others) up 0.0089 0.2731 11732546_at DEFA4 defensin, alpha 4, corticostatin Extracellular Space other up 0 1.5703 ILMN_1753347 DEFA4 up 0.0038 0.4375 DEFA4 19024344 DEFA4 along with DEFA1 and DEFA3 are cationic alpha-defensin peptides that have multiple functions in the immune system. 11737096_a_at DSC2 desmocollin 2 Plasma Membrane other up 0.0069 0.6753 ILMN_1782125 DSC2 up 0.0054 0.3338 11757702_s_at DSC2 desmocollin 2 Plasma Membrane other up 0.0081 0.6023 11725531_a_at DSC2 desmocollin 2 Plasma Membrane other up 0.0135 0.4412 11722573_a_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase down 0.0007 -1.0458 ILMN_1743145 ERAP2 down 0 -1.0179 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase down 0.0282 -0.6277 11762512_a_at ERICH1 glutamate-rich 1 unknown other down 0.0079 -0.7043 ILMN_1904238 ERICH1 down 0 -0.5209 11720023_a_at FAM118A family with sequence similarity 118, member A unknown other down 0.0438 -0.3324 ILMN_1809147 FAM118A down 0.0012 -0.226 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other down 0.0384 -0.6956 ILMN_1687213 FAM167A down 0.0099 -0.1587 11744141_x_at FOLR3 folate receptor 3 (gamma) Extracellular Space other down 0.0076 -0.4784 ILMN_1730454 FOLR3 updown 0.0036 0.0003 -0.1031 -0.1031 11744140_a_at FOLR3 folate receptor 3 (gamma) Extracellular Space other down 0.0145 -0.4848 11763755_a_at GNLY granulysin Cytoplasm other down 0.0024 -0.887 ILMN_1708779 GNLY down 0.0277 -0.1002 11718579_at GSTM3 glutathione S-transferase mu 3 (brain) Cytoplasm enzyme up 0.0027 0.6341 ILMN_1736184 GSTM3 up 0.038 0.1065 11718578_a_at GSTM3 glutathione S-transferase mu 3 (brain) Cytoplasm enzyme up 0.0069 0.1499 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other up 0.0021 0.0784 ILMN_1721113 HLA-C up 0.0008 0.3324 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor down 0 -5.2313 ILMN_1749070 HLA-DPB1 down 0.0012 -0.3886 11760878_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor down 0 -1.3411 11757480_x_at IFI27 interferon, alpha-inducible protein 27 Cytoplasm other up 0 0.8924 ILMN_1661581 IFI27 up 0.0208 -0.0279 IFI27 20939681 IFI27 is a mitochondrial protein and its expression sensitizes cells to apoptotic stimuli via mitochondrial membrane destabilization. 11715893_s_at IFI27 interferon, alpha-inducible protein 27 Cytoplasm other up 0.0195 0.2029 11723236_at IFI44L interferon-induced protein 44-like unknown other up 0.0463 0.3524 ILMN_1723912 IFI44L up 0.0039 0.4923 18332133 IRF5 is activated by both TBK1 and MYD88 to form a homodimer that binds to and activates transcription of type I interferon and inflammatory cytokine genes. 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator up 0 0.7449 ILMN_1670576 IRF5 up 0.0155 0.209 IRF5 12600985 IRF5 can act as both an activator and a repressor of interferon (IFN) gene induction dependent on the IRF-interacting partner, and may be a part of the regulatory network that ensures timely expression of the immediate early inflammatory genes. 11757634_a_at LCN2 lipocalin 2 Extracellular Space transporter up 0 0.923 ILMN_1692223 LCN2 up 0 0.4521 22412986 Phosphorylation of IRF5 at ser451 and ser462 is the primary trigger of IRF5 function in nuclear accumulation, transcription and apoptosis. 11715461_at LYZ lysozyme Extracellular Space enzyme up 0.0122 -0.0812 ILMN_1815205 LYZ up 0.0032 0.1535 11736090_a_at OLIG2 oligodendrocyte lineage transcription factor 2 Nucleus transcription regulator up 0.0071 0.5582 ILMN_1727567 OLIG2 up 0.0031 0.3068 11744904_a_at ORM1 orosomucoid 1 Extracellular Space other down 0 -1.1656 ILMN_1696584 ORM1 down 0.004 -0.4264 11744905_x_at ORM1 orosomucoid 1 Extracellular Space other down 0.0011 -0.9922 11754065_x_at ORM1 orosomucoid 1 Extracellular Space other down 0.0028 -1.0052 11758794_x_at ORM1 orosomucoid 1 Extracellular Space other down 0.0036 -0.8664 11723303_at PDZK1IP1 PDZK1 interacting protein 1 Extracellular Space other down 0 -1.085 ILMN_1708580 PDZK1IP1 down 0.0175 -0.1934 11755743_a_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme up 0.0093 0.5361 ILMN_1730628 RNASE2 up 0.0041 0.2203 11729772_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme up 0.0459 0.3627 11732801_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other up 0 0.7194 ILMN_1675424 SIRPB1 up 0.0412 0.2506 11732800_a_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other up 0.0068 0.2539 11752660_a_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other up 0.0156 0.031 11736145_a_at SPATA20 spermatogenesis associated 20 unknown other down 0.0077 -0.6376 ILMN_1687247 SPATA20 down 0.0038 -0.0039 11736523_x_at TNNT1 troponin T type 1 (skeletal, slow) Cytoplasm other up 0.0461 0.7909 ILMN_1717297 TNNT1 up 0.0413 0.2452 11756497_a_at VWCE von Willebrand factor C and EGF domains unknown other down 0.0207 -0.6441 ILMN_1760315 VWCE down 0.0047 -0.2535 Diabetes Page 86 of 111

Differentially expressed genes 6-18 months after seroconversion (FDR < 0.05) showing concordant changes in Affymetrix and Illumina arrays, and information regarding the innate immunity function of the genes (InnateDB)

AFFYMETRIX Case vs. control ILLUMINA Case vs. control InnateDB (www.innatedb.org) Innate Immunity Genes in human. P value for enrichment is 0.000000000048. Affymetrix ID Gene Symbol (IPA) Gene name (IPA) Location (IPA) Type (IPA) Drug (IPA) Change probeset FDR max FDR min SLR max SLR min Illumina ID Gene Symbol (IPA) Change probeFDR max FDR min SLR max SLR min Gene Symbol (human)Pubmed ID Annotation 11747858_a_at ABCE1 ATP-binding cassette, sub-family E (OABP), member 1 Cytoplasm transporter down 0.0049 -0.8153 ILMN_1676846 ABCE1 down 0.0026 -0.4453 11730238_a_at ABHD10 abhydrolase domain containing 10 Cytoplasm enzyme down 0.0444 -0.6627 ILMN_1770031 ABHD10 down 0.0003 -0.4466 11746269_a_at ABHD3 abhydrolase domain containing 3 unknown enzyme down 0.0079 -0.7418 ILMN_1801767 ABHD3 down 0.0006 -0.465 11746834_a_at ACADM acyl-CoA dehydrogenase, C-4 to C-12 straight chain Cytoplasm enzyme down 0.0189 -0.6415 ILMN_1778104 ACADM down 0.0043 -0.3998 11747344_a_at ACADM acyl-CoA dehydrogenase, C-4 to C-12 straight chain Cytoplasm enzyme down 0.0307 -0.5232 11747346_x_at ACADM acyl-CoA dehydrogenase, C-4 to C-12 straight chain Cytoplasm enzyme down 0.0346 -0.7591 11747345_s_at ACADM acyl-CoA dehydrogenase, C-4 to C-12 straight chain Cytoplasm enzyme down 0.0346 -0.6132 11754458_a_at ACRBP acrosin binding protein Extracellular Space other down 0.0382 -0.5611 ILMN_1784203 ACRBP down 0.0177 -0.3429 11750700_a_at ACSL1 acyl-CoA synthetase long-chain family member 1 Cytoplasm enzyme down 0.0003 -0.7883 ILMN_1684585 ACSL1 updown 0.0026 0.0002 0.2867 -0.3251 11721452_a_at ACTR6 ARP6 actin-related protein 6 homolog (yeast) unknown transporter down 0.0001 -1.0422 ILMN_1697585 ACTR6 down 0 -0.574 11763741_x_at ACTR6 ARP6 actin-related protein 6 homolog (yeast) unknown transporter down 0.0116 -0.7947 11763740_a_at ACTR6 ARP6 actin-related protein 6 homolog (yeast) unknown transporter down 0.012 -0.6489 11753175_a_at ADIPOR1 adiponectin receptor 1 Plasma Membrane transmembrane receptor up 0.0462 0.6582 ILMN_1688322 ADIPOR1 up 0 0.6366 11756406_x_at ADM adrenomedullin Extracellular Space other down 0 -0.7841 ILMN_1708934 ADM updown 0.0053 0 0.0972 -0.8186 11716710_a_at ADM adrenomedullin Extracellular Space other down 0.0001 -0.7018 11753618_a_at ADM adrenomedullin Extracellular Space other down 0.0055 -0.6955 11726230_s_at AHI1 Abelson helper integration site 1 Cytoplasm other down 0.0032 -0.5844 ILMN_1791006 AHI1 down 0.0072 -0.3019 20351692 AIM2 inflammasome is essential for host defence against cytosolic bacteria and DNA viruses. 11754693_a_at AHI1 Abelson helper integration site 1 Cytoplasm other down 0.0077 -0.5834 20401524 AIM2 is a newly discovered pattern recognition receptor (PRR) involved in the sensing of dangerous cytosolic DNA produced by infection with DNA viruses. 11718997_at AHSP alpha hemoglobin stabilizing protein Cytoplasm other up 0.0054 0.8011 ILMN_1696512 AHSP up 0.0021 0.3804 20351693 AIM2 has a critical role in host innate immunity to intracellular pathogens where it is a crucial sensor of F. tularensis infection. 11730457_a_at AIM2 absent in melanoma 2 Cytoplasm other down 0.0001 -0.8371 ILMN_1681301 AIM2 down 0.0001 -0.4994 AIM2 21562230 AIM2-containing inflammasomes are activated in response to cytosolic DNA, Â this response is augmented in keratinocytes from psoriatic lesions and contributes to the auto-inflammatory disease. 11730458_at AIM2 absent in melanoma 2 Cytoplasm other down 0.0004 -0.6756 20457908 AIM2 is required for innate immune recognition of Francisella tularensis where AIM2-deficient mice display an increased susceptibility to F. tularensis infection compared with wild-type mice. 11723804_a_at AKAP12 A kinase (PRKA) anchor protein 12 Cytoplasm transporter up 0.005 0.6906 ILMN_1686846 AKAP12 up 0.0289 0.2553 19158675 AIM2 recognizes cytosolic double stranded DNA and forms a caspase-1-activating inflammasome with PYCARD (ASC). 11722595_a_at AKAP13 A kinase (PRKA) anchor protein 13 Cytoplasm other up 0.0242 0.5967 ILMN_1752247 AKAP13 up 0.0169 0.3176 11715711_a_at AKR1C3 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase,Cytoplasm type II) enzyme down 0.0001 -0.7788 ILMN_1713124 AKR1C3 down 0 -0.5008 11734745_a_at ALAS2 aminolevulinate, delta-, synthase 2 Cytoplasm enzyme up 0.0002 0.6561 ILMN_1708323 ALAS2 up 0 0.4956 11758412_s_at ALAS2 aminolevulinate, delta-, synthase 2 Cytoplasm enzyme up 0.0002 0.619 11738208_a_at ALAS2 aminolevulinate, delta-, synthase 2 Cytoplasm enzyme up 0.0013 0.5229 11721753_a_at ALG13 asparagine-linked glycosylation 13 homolog (S. cerevisiae) Cytoplasm enzyme down 0.0001 -0.8604 ILMN_1761456 ALG13 down 0.0065 -0.3172 11721755_at ALG13 asparagine-linked glycosylation 13 homolog (S. cerevisiae) Cytoplasm enzyme down 0.0008 -0.7185 11721754_x_at ALG13 asparagine-linked glycosylation 13 homolog (S. cerevisiae) Cytoplasm enzyme down 0.0017 -0.6955 11748032_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase updown 0.0005 0.0001 0.4516 -0.4281 ILMN_1701603 ALPL updown 0 0 0.3095 -0.5921 11748031_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase updown 0.0004 0.0001 0.5075 -0.3036 11729336_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase updown 0.0011 0.0001 0.4877 -0.3252 11729337_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase updown 0.0016 0.0001 0.4412 -0.2555 11750919_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase updown 0.0003 0.0003 0.6709 -0.3183 11726243_a_at ANKDD1A ankyrin repeat and death domain containing 1A unknown other down 0.0129 -0.481 ILMN_1813139 ANKDD1A down 0.0322 -0.1167 11737650_at ANKFY1 ankyrin repeat and FYVE domain containing 1 Nucleus transcription regulator up 0.0099 0.6461 ILMN_1794470 ANKFY1 up 0.0035 0.3715 11737649_a_at ANKFY1 ankyrin repeat and FYVE domain containing 1 Nucleus transcription regulator up 0.0145 0.6169 11721747_a_at ANKRD12 ankyrin repeat domain 12 Nucleus other down 0.0112 -0.6765 ILMN_1661833 ANKRD12 down 0.0001 -0.5318 11732425_at ANKRD22 ankyrin repeat domain 22 Nucleus transcription regulator up 0 0.6403 ILMN_1799848 ANKRD22 up 0.0029 0.1873 11732424_at ANKRD22 ankyrin repeat domain 22 Nucleus transcription regulator up 0.0002 0.4979 11757989_s_at ANKRD46 ankyrin repeat domain 46 Nucleus transcription regulator down 0.0232 -0.6602 ILMN_1712298 ANKRD46 down 0 -0.5728 11758059_s_at ANKRD49 ankyrin repeat domain 49 Nucleus transcription regulator down 0.0049 -0.7115 ILMN_1669259 ANKRD49 down 0 -0.6348 11724283_a_at ANXA3 annexin A3 Cytoplasm enzyme down 0 -1.4857 ILMN_1694548 ANXA3 down 0.0007 -0.3834 11756334_x_at ANXA3 annexin A3 Cytoplasm enzyme down 0 -1.5396 11727629_at APBA2 amyloid beta (A4) precursor protein-binding, family A, member 2 Cytoplasm transporter up 0.0352 0.5352 ILMN_1723626 APBA2 up 0.0384 0.2248 11748557_a_at APIP APAF1 interacting protein Cytoplasm enzyme down 0.0008 -0.8503 ILMN_1793598 APIP down 0.0381 -0.3013 11720834_a_at APIP APAF1 interacting protein Cytoplasm enzyme down 0.0198 -0.6077 11736632_at APOBEC3H apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3H Cytoplasm enzyme down 0.0015 -0.5092 ILMN_1664828 APOBEC3H down 0.0025 -0.255 11733855_a_at APOL1 apolipoprotein L, 1 Extracellular Space transporter up 0.0164 0.5733 ILMN_1761793 APOL1 up 0.0175 0.2509 11741187_a_at APOL1 apolipoprotein L, 1 Extracellular Space transporter up 0.0229 0.521 11735998_a_at APOL1 apolipoprotein L, 1 Extracellular Space transporter up 0.0294 0.5274 11742449_a_at APOL1 apolipoprotein L, 1 Extracellular Space transporter up 0.0354 0.5563 11753920_a_at APOL1 apolipoprotein L, 1 Extracellular Space transporter up 0.0369 0.605 11725701_a_at AQP9 aquaporin 9 Plasma Membrane transporter down 0.0011 -0.8344 ILMN_1715068 AQP9 updown 0.0112 0 0.3773 -0.5104 11749906_a_at AQP9 aquaporin 9 Plasma Membrane transporter down 0.0045 -0.6353 11754669_a_at ARG1 arginase, liver Cytoplasm enzyme down 0 -0.8934 ILMN_1812281 ARG1 down 0.0014 -0.3494 ARG1 18978793 ARG1 expression induced by intracellular pathogens in mouse classically activated macrophages (CAMs) through the TLR pathway, suppressing nitric oxide production and thwarting effective immunity independent of the STAT6 pathway. 11754241_a_at ATAD1 ATPase family, AAA domain containing 1 Cytoplasm enzyme down 0.0087 -0.5986 ILMN_1654497 ATAD1 down 0.0005 -0.4704 11729306_s_at ATAD1 ATPase family, AAA domain containing 1 Cytoplasm enzyme down 0.01 -0.7433 11754592_x_at ATF5 activating transcription factor 5 Nucleus transcription regulator up 0.0498 0.5644 ILMN_1669113 ATF5 up 0.0004 0.4183 11759680_a_at ATG3 autophagy related 3 Cytoplasm enzyme down 0.0136 -0.6706 ILMN_1769566 ATG3 down 0.0096 -0.2853 11721239_x_at ATP5L ATP synthase, H+ transporting, mitochondrial Fo complex, subunit G Cytoplasm transporter down 0.0097 -0.7565 ILMN_1812638 ATP5L down 0.0001 -0.4058 11721238_s_at ATP5L ATP synthase, H+ transporting, mitochondrial Fo complex, subunit G Cytoplasm transporter down 0.0167 -0.7477 11718943_a_at AURKA aurora kinase A Nucleus kinase tozasertib, MLN8054down 0.0221 -0.4654 ILMN_1680955 AURKA down 0.005 -0.2795 11728909_s_at B3GALTL beta 1,3-galactosyltransferase-like unknown other down 0.0032 -0.6796 ILMN_1764813 B3GALTL down 0.0001 -0.378 11730096_a_at BCL2A1 BCL2-related protein A1 Cytoplasm other down 0 -1.6299 ILMN_1769229 BCL2A1 down 0.0392 -0.2296 BCL2A1 21167304 BCL2A1 negatively regulates autophagy and expression of BCL2A1 in Mycobacterium tuberculosis infected macrophages provides the bacteria a survival strategy to overcome host defences. 11739958_x_at BCL2L1 BCL2-like 1 Cytoplasm other up 0.015 0.6602 ILMN_1742410 BCL2L1 up 0.0031 0.1227 11759322_at BCL6 B-cell CLL/lymphoma 6 Nucleus transcription regulator updown 0.0432 0.0123 0.56 -0.4636 ILMN_1737314 BCL6 updown 0.0156 0.0013 0.2405 -0.3607 11750749_a_at BCL6 B-cell CLL/lymphoma 6 Nucleus transcription regulator down 0.0195 -0.5289 11739841_a_at BCL6 B-cell CLL/lymphoma 6 Nucleus transcription regulator down 0.026 -0.5517 11719815_at BET1 blocked early in transport 1 homolog (S. cerevisiae) Cytoplasm transporter down 0.0204 -0.6887 ILMN_1684042 BET1 down 0.0123 -0.3387 11723420_s_at BTF3L4 basic transcription factor 3-like 4 unknown other down 0 -1.1341 ILMN_1759359 BTF3L4 down 0.0279 -0.3165 11735222_a_at BTLA B and T lymphocyte associated Plasma Membrane other down 0.0015 -0.7439 ILMN_1778536 BTLA down 0.0472 -0.2714 11728357_s_at C10orf88 chromosome 10 open reading frame 88 unknown other down 0.0024 -0.7964 ILMN_1775423 C10orf88 down 0.0048 -0.3468 11723560_at C11orf75 chromosome 11 open reading frame 75 unknown other down 0.0282 -0.3538 ILMN_1798270 C11orf75 updown 0.0212 0.0219 0.2755 -0.4041 11727525_a_at C12orf29 chromosome 12 open reading frame 29 unknown other down 0.0104 -0.589 ILMN_1792671 C12orf29 down 0.0003 -0.494 11724786_s_at C14orf129 chromosome 14 open reading frame 129 unknown other down 0.0007 -0.9484 ILMN_1712748 C14orf129 down 0.0051 -0.4539 11716875_at C14orf142 chromosome 14 open reading frame 142 unknown other down 0.0001 -0.989 ILMN_1685781 C14orf142 down 0.003 -0.3376 11743264_x_at C14orf2 chromosome 14 open reading frame 2 Cytoplasm other down 0 -0.8828 ILMN_1652722 C14orf2 down 0 -0.7013 11758135_s_at C14orf2 chromosome 14 open reading frame 2 Cytoplasm other down 0.0027 -0.7466 11737309_x_at C14orf2 chromosome 14 open reading frame 2 Cytoplasm other down 0.0042 -0.74 11763751_x_at C14orf2 chromosome 14 open reading frame 2 Cytoplasm other down 0.037 -0.5631 11755220_a_at C17orf97 chromosome 17 open reading frame 97 unknown other down 0.0001 -0.6895 ILMN_1707137 C17orf97 down 0.0001 -0.3294 11725888_at C19orf59 chromosome 19 open reading frame 59 unknown other down 0 -0.8453 ILMN_1762713 C19orf59 updown 0.0013 0 0.1951 -0.6858 11725889_at C19orf59 chromosome 19 open reading frame 59 unknown other down 0.0001 -0.5538 11726618_a_at C1GALT1C1 C1GALT1-specific chaperone 1 Cytoplasm enzyme down 0.0004 -0.8671 ILMN_1751234 C1GALT1C1 down 0.0005 -0.409 11743934_a_at C1GALT1C1 C1GALT1-specific chaperone 1 Cytoplasm enzyme down 0.001 -0.8067 11726619_s_at C1GALT1C1 C1GALT1-specific chaperone 1 Cytoplasm enzyme down 0.0031 -0.7857 11717045_a_at C2 complement component 2 Extracellular Space peptidase up 0.0004 0.8467 ILMN_1710740 C2 up 0.0311 0.1384 C2 12791093 C2 is part of the classical and lectin complement pathways 11757208_s_at C22orf34 chromosome 22 open reading frame 34 unknown other up 0.0208 0.6709 ILMN_1717371 C22orf34 up 0.0145 0.2243 11044372 C2 molecule binds to C4B and is cleaved by C1S protease into C2A and C2B fragments and the resulting C4B2A complex (C3 convertase) is the active protease which cleaves C3 11721099_at C3AR1 complement component 3a receptor 1 Plasma Membrane G-protein coupled receptor up 0.0109 0.6168 ILMN_1787529 C3AR1 up 0 0.5499 11723949_a_at C4BPA complement component 4 binding protein, alpha Extracellular Space other up 0 2.436 ILMN_1810752 C4BPA up 0.0001 0.3267 C4BPA 21283780 C4BPA plays an inhibitory role in antimicrobial response by delaying the classical complement activation and attenuating the lectin pathway activation. The major inhibitory role of C4BPA is to facilitate the decay of C3 convertase. 11744719_x_at C4BPA complement component 4 binding protein, alpha Extracellular Space other up 0 2.1461 11748570_a_at C5orf4 chromosome 5 open reading frame 4 unknown other up 0 0.7521 ILMN_1728742 C5orf4 up 0.0403 0.2577 11751501_a_at C5orf4 chromosome 5 open reading frame 4 unknown other up 0 0.9206 11755573_s_at C5orf4 chromosome 5 open reading frame 4 unknown other up 0.0004 0.563 11716889_at C9orf123 chromosome 9 open reading frame 123 unknown other down 0.0017 -0.715 ILMN_1769409 C9orf123 updown 0.0138 0 0.3804 -0.4419 11758239_s_at C9orf72 chromosome 9 open reading frame 72 unknown other down 0.0026 -0.5802 ILMN_1741881 C9orf72 down 0.0001 -0.4281 11729583_x_at CA1 carbonic anhydrase I Cytoplasm enzyme methazolamide, hydrochlorothiazide,up acetazolamide,0.0002 trichloromethiazide, dorzolamide,0.5452 chlorothiazide,ILMN_1652431 dorzolamide/timolol,CA1 brinzolamide, chlorthalidone,up benzthiazide,0.0022 sulfacetamide, topiramate0.2609 11729582_s_at CA1 carbonic anhydrase I Cytoplasm enzyme methazolamide, hydrochlorothiazide,up acetazolamide,0.0004 trichloromethiazide, dorzolamide,0.7108 chlorothiazide, dorzolamide/timolol, brinzolamide, chlorthalidone, benzthiazide, sulfacetamide, topiramate 11729014_at CACNA1E calcium channel, voltage-dependent, R type, alpha 1E subunit Plasma Membrane ion channel down 0.0024 -0.6577 ILMN_1664047 CACNA1E down 0.0086 -0.2199 11742124_a_at CACNG6 calcium channel, voltage-dependent, gamma subunit 6 Plasma Membrane ion channel up 0.0005 0.4396 ILMN_1779043 CACNG6 up 0.0004 0.4591 11731645_a_at CAMKK2 calcium/calmodulin-dependent protein kinase kinase 2, beta Cytoplasm kinase up 0.049 0.7012 ILMN_1743021 CAMKK2 up 0.0004 0.4925 CAMKK2 22334678 CAMKK2-null macrophages exhibited deficiency to spread, phagocytize bacteria and synthesize cytokines in response to the Toll Like Receptor 4 (TLR4) agonist lipopolysaccharide (LPS). (Demonstrated in mice) 11726688_at CAMP cathelicidin antimicrobial peptide Cytoplasm other down 0.0003 -0.9631 ILMN_1688580 CAMP down 0 -0.4978 CAMP 22031815 LL-37 (CAMP) reduces influenza A viral load and disease severity in mice. 11748404_s_at CAMSAP2 calmodulin regulated spectrin-associated protein family, member 2 unknown other down 0.0062 -0.6248 ILMN_1792660 CAMSAP2 down 0.0139 -0.3171 21832078 CAMP expression is induced upon endoplasmic reticulum stress via NF-kB-C/EBP-alpha activation. 11739007_at CAPZA1 capping protein (actin filament) muscle Z-line, alpha 1 Cytoplasm other down 0.0315 -0.6163 ILMN_1803742 CAPZA1 down 0.0044 -0.4131 21448240 CAMP (LL-37), at sufficiently low concentrations, is able to reduce fungal infectivity by inhibiting C. albicans adhesion to plastic surfaces, oral epidermoid cells, and the urinary bladders of female mice. The inhibitory effects of LL-37 on cell adhesion 11723013_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0001 -1.0872 ILMN_1768870 CAPZA2 down 0 -0.7106 21562230 CAMP (LL-37) confers protective immunity against psoriasis by neutralizing cytosolic DNA in keratinocytes and blocking the formation of AIM2 inflammasomes. 11723012_a_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0004 -0.8709 21762664 CAMP protects against colitis induction in mice. The increased expression of CAMP in monocytes involves the activation of TLR9/ERK signalling pathway by bacterial DNA. (Demonstrated in mouse) 11747046_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0007 -0.9028 23328115 CAMP (LL-37) is downregulated during septic shock. 11750192_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0007 -0.7195 21464330 CAMP (LL-37) translocates across the E. coli outer membrane and halts bacterial growth by interfering cell wall biogenesis. 11717805_a_at CASP3 caspase 3, apoptosis-related cysteine peptidase Cytoplasm peptidase IDN-6556 down 0.0007 -0.7327 ILMN_1756787 CASP3 down 0 -0.6294 19625657 CAMP represents a potent antimicrobial and cell-stimulating agent, most abundantly expressed in peripheral organs such as lung and skin during inflammation. 11719839_a_at CASP3 caspase 3, apoptosis-related cysteine peptidase Cytoplasm peptidase IDN-6556 down 0.0036 -0.7914 19748465 CAMP, a protein that has direct antimicrobial activity, serves as a mediator of vitamin D3-induced autophagy. 11719838_a_at CASP3 caspase 3, apoptosis-related cysteine peptidase Cytoplasm peptidase IDN-6556 down 0.0136 -0.5863 19812202 CAMP (LL-37) modulates IFN-gamma responses during both the innate and adaptive phases of immune responses, indicating an immunomodulatory role for this endogenous peptide. 11731726_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase updown 0.0032 0 0.5663 -1.2268 ILMN_1722158 CASP5 updown 0.0009 0 0.2182 -0.4435 18397922 CAMP induces endothelium-dependent relaxation in human omental veins, or vasodilation, mediated via an effect on endothelial ALX. 11753343_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase updown 0.0004 0 0.8263 -1.0892 18923446 CAMP is involved in various aspects of skin biology, including protection against infection, wound healing, and also in psoriasis where it suppresses apoptosis in keratinocytes. 11731727_x_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase updown 0.0008 0 0.5358 -0.9828 20036634 CAMP has dual function as an antimicrobial agent against bacterial target cells and a cell penetrating peptide that can deliver nucleic acids into the host cells. 11744286_s_at CBS cystathionine-beta-synthase Cytoplasm enzyme down 0.0294 -0.6136 ILMN_1804735 CBS updown 0.0228 0.0113 0.2327 -0.2765 19797203 CAMP has both antimicrobial and regenerative capabilities and promotes high glucose-attenuated epithelial wound healing via EGFR transactivation in organ cultured corneas. 11738292_x_at CCDC132 coiled-coil domain containing 132 unknown other down 0.0262 -0.6938 ILMN_1716342 CCDC132 down 0.0174 -0.3773 20163451 CAMP decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs) and this inhibition is dependent on phosphorylation of extracellular signal-regulated kinase (ERK). Vitamin C attenuates ERK signalling to inhibit the regulat 11756908_a_at CCDC132 coiled-coil domain containing 132 unknown other down 0.0405 -0.711 20190140 CAMP and human beta-defensins (hBDs) antimicrobial peptides induce the secretion of a pruritogenic cytokine IL-31 by human mast cells. 11733454_a_at CCDC41 coiled-coil domain containing 41 Extracellular Space other down 0.001 -0.8413 ILMN_1799113 CCDC41 down 0.0165 -0.2403 21441450 CAMP (LL-37) dramatically reduced TNFA and nitric oxide levels produced by LPS and IFNG-polarized M1 macrophages, in addition LL-37-treated M1 macrophages were more efficient at suppressing tumour growth in vitro. This demonstrates the selective ability o 11752380_a_at CCDC41 coiled-coil domain containing 41 Extracellular Space other down 0.0242 -0.4863 20610648 CAMP (LL37) directs macrophage differentiation toward macrophages with a pro-inflammatory signature and this requires internalization of the peptide, resulting in low production of IL-10 and profound production of IL-12p40 upon LPS stimulation. 11758576_s_at CCDC59 coiled-coil domain containing 59 unknown other down 0.0041 -0.7324 ILMN_1662318 CCDC59 down 0.0011 -0.4203 19703986 CAMP (LL37) converts self-RNA into a trigger of TLR7 and TLR8 in human dendritic cells (DC), leading to production of TNF-alpha and IL6 and the differentiation of myeloid DCs into mature DCs. 11736416_s_at CCDC82 coiled-coil domain containing 82 unknown other down 0 -1.2768 ILMN_1791933 CCDC82 down 0.0007 -0.2801 21393634 CAMP (LL-37) attenuates lethal sepsis/endotoxin shock by suppressing the LPS-induced apoptosis of vascular and hepatic endothelial cells. LL-37 was found to inhibit the binding of LPS to the LPS receptors expressed on the cells. 11744442_at CCDC82 coiled-coil domain containing 82 unknown other down 0 -1.1984 21389264 CAMP (LL37) is found in high concentrations within neutrophil extracellular traps (NETs). CAMP is a neutrophil protein that facilitates the uptake and recognition of mammalian DNA by plasmacytoid dendritic cells, and may play a role in Systemic Lupus Erth 11744443_x_at CCDC82 coiled-coil domain containing 82 unknown other down 0 -1.0666 20042575 CAMP enhances delivery of CpG oligodeoxynucleotides to stimulate immune cells and this is independent of its amphipathic structure and its bactericidal property. 11736417_a_at CCDC82 coiled-coil domain containing 82 unknown other down 0.0015 -0.7637 11744660_s_at CCL4L1/CCL4L2 chemokine (C-C motif) ligand 4-like 1 Plasma Membrane other down 0.0437 -0.3548 ILMN_1716276 CCL4L1/CCL4L2 down 0.0135 -0.3226 11728039_s_at CCL8 chemokine (C-C motif) ligand 8 Extracellular Space cytokine up 0 0.7243 ILMN_1772964 CCL8 up 0 0.3484 11716793_a_at CCNB2 cyclin B2 Cytoplasm other down 0 -0.792 ILMN_1801939 CCNB2 down 0.0016 -0.2361 11726983_s_at CCNC cyclin C Nucleus other down 0.0174 -0.6203 ILMN_1676423 CCNC down 0.0007 -0.5034 11726985_x_at CCNC cyclin C Nucleus other down 0.0339 -0.6679 11726081_a_at CCNT2 cyclin T2 Nucleus transcription regulator down 0.0001 -0.8853 ILMN_1722522 CCNT2 down 0.019 -0.3148 11750856_s_at CCR2 chemokine (C-C motif) receptor 2 Plasma Membrane G-protein coupled receptor down 0.0041 -0.6298 ILMN_1769895 CCR2 down 0.0003 -0.4343 11752590_s_at CCR2 chemokine (C-C motif) receptor 2 Plasma Membrane G-protein coupled receptor down 0.0147 -0.573 ILMN_1774761 CCR2 down 0.0014 -0.3237 11747113_a_at CD160 CD160 molecule Plasma Membrane transmembrane receptor down 0.0486 -0.6548 ILMN_1742001 CD160 down 0.0005 -0.5058 11749610_a_at CD58 CD58 molecule Plasma Membrane other down 0.0001 -0.8228 ILMN_1785268 CD58 down 0.0114 -0.4117 11754000_x_at CD58 CD58 molecule Plasma Membrane other down 0.0007 -0.7996 11724689_a_at CD58 CD58 molecule Plasma Membrane other down 0.0015 -0.7369 11753998_a_at CD58 CD58 molecule Plasma Membrane other down 0.0025 -0.7709 11750359_x_at CD68 CD68 molecule Plasma Membrane other up 0.0105 0.4975 ILMN_1714861 CD68 up 0.0018 0.3011 11729741_x_at CD68 CD68 molecule Plasma Membrane other up 0.0125 0.5576 11717163_s_at CDC20 cell division cycle 20 homolog (S. cerevisiae) Nucleus other down 0.0051 -0.615 ILMN_1663390 CDC20 down 0.0003 -0.3746 11732058_a_at CDC7 cell division cycle 7 homolog (S. cerevisiae) Nucleus kinase down 0.0079 -0.8918 ILMN_1741801 CDC7 down 0.0182 -0.2138 11718183_at CDCA5 cell division cycle associated 5 Cytoplasm other down 0.0058 -0.5309 ILMN_1683450 CDCA5 down 0.0016 -0.2535 11722022_s_at CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35) Nucleus kinase down 0.049 -0.4214 ILMN_1730928 CDK5R1 down 0.0095 -0.1754 11715387_at CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1) Nucleus kinase up 0.0271 0.6746 ILMN_1784602 CDKN1A up 0.0028 0.3691 11763718_x_at CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2) Nucleus other up 0 0.9814 ILMN_1718565 CDKN1C up 0.0261 0.2649 11763717_a_at CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2) Nucleus other up 0.0001 0.6973 11764032_at CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2) Nucleus other up 0.0004 0.7591 11729118_a_at CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2) Nucleus other up 0.0142 0.7009 11721666_at CDT1 chromatin licensing and DNA replication factor 1 Nucleus other down 0.0075 -0.5429 ILMN_1651237 CDT1 down 0.004 -0.2937 11751094_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other updown 0.0016 0.0087 0.4111 -0.4883 ILMN_1716815 CEACAM1 updown 0.0028 0.0002 0.2231 -0.4752 CEACAM1 18836450 CEACAM1 inhibits TLR2 induced pro-inflammatory immune responses by inducing PTPN6-(SHP-1)-mediated inhibition of the PI3K-NF-kappaB signal transduction pathway in pulmonary epithelial cells. 11760081_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other updown 0.0196 0.0175 0.4641 -0.4142 ILMN_1664330 CEACAM1 updown 0.0042 0.0002 0.3431 -0.3969 11756058_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other updown 0.0067 0.018 0.7128 -0.6289 11753506_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other updown 0.0055 0.0223 0.6313 -0.6099 11751217_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other updown 0.0087 0.0223 0.6221 -0.5585 11751095_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other updown 0.006 0.0264 0.618 -0.6586 11758685_s_at CEACAM8 carcinoembryonic antigen-related cell adhesion molecule 8 Plasma Membrane other down 0 -0.6713 ILMN_1806056 CEACAM8 down 0.0115 -0.246 11750177_x_at CEACAM8 carcinoembryonic antigen-related cell adhesion molecule 8 Plasma Membrane other down 0.0036 -0.6025 11734346_at CEBPE CCAAT/enhancer binding protein (C/EBP), epsilon Nucleus transcription regulator up 0.0023 0.5355 ILMN_1779095 CEBPE up 0.0026 0.3018 CEBPE 21326902 CEBPE is a member of the CCAAT enhancer binding protein family and is a transcriptional factor regulating genes in innate immunity and inflammation. The activities of CEBP are regulated via methylation of arginine and lysine side chains. 11732601_at CEP135 centrosomal protein 135kDa Cytoplasm other down 0.0392 -0.6061 ILMN_1693766 CEP135 down 0.0016 -0.5212 11720247_a_at CEP55 centrosomal protein 55kDa Cytoplasm other down 0 -0.8504 ILMN_1747016 CEP55 down 0 -0.3721 11758261_s_at CEP55 centrosomal protein 55kDa Cytoplasm other down 0.0001 -0.6851 11759323_at CEP85L centrosomal protein 85kDa-like Cytoplasm other down 0.0102 -0.6946 ILMN_1855286 CEP85L down 0.0001 -0.3817 11725980_at CFD complement factor D (adipsin) Extracellular Space peptidase updown 0.0498 0.0432 0.6214 -0.3127 ILMN_1777190 CFD updown 0.0054 0.0095 0.3853 -0.0197 11758806_at CGRRF1 cell growth regulator with ring finger domain 1 unknown other down 0.0004 -0.7745 ILMN_1681008 CGRRF1 down 0.0095 -0.3234 11719127_s_at CGRRF1 cell growth regulator with ring finger domain 1 unknown other down 0.0072 -0.7446 11719126_a_at CGRRF1 cell growth regulator with ring finger domain 1 unknown other down 0.028 -0.7554 11754262_s_at CHD9 chromodomain helicase DNA binding protein 9 Cytoplasm other down 0.018 -0.6567 ILMN_1762972 CHD9 down 0.0217 -0.3443 11718655_s_at CHMP5 charged multivesicular body protein 5 Cytoplasm other down 0.0015 -0.6055 ILMN_1732534 CHMP5 down 0.0021 -0.3444 11760624_at CHMP5 charged multivesicular body protein 5 Cytoplasm other down 0.029 -0.6044 11730536_at CHST13 carbohydrate (chondroitin 4) sulfotransferase 13 Cytoplasm enzyme up 0.0422 0.5502 ILMN_1734707 CHST13 updown 0.0075 0.0132 0.0162 -0.1851 Page 87 of 111 Diabetes

11721504_a_at CKLF chemokine-like factor Extracellular Space cytokine down 0.0001 -0.898 ILMN_1712389 CKLF down 0 -0.6079 11720679_a_at CKLF chemokine-like factor Extracellular Space cytokine down 0.0043 -0.7426 11716092_x_at CKS1B CDC28 protein kinase regulatory subunit 1B unknown kinase down 0.0262 -0.4939 ILMN_1719256 CKS1B down 0.0116 -0.2812 11753856_a_at CKS2 CDC28 protein kinase regulatory subunit 2 unknown kinase down 0.0001 -0.748 ILMN_1756326 CKS2 down 0.0087 -0.2495 11727473_at CLC Charcot-Leyden crystal protein Cytoplasm enzyme updown 0.0272 0.0068 0.4041 -0.2565 ILMN_1654875 CLC updown 0 0 0.3086 -0.2382 11744641_a_at CLDND1 claudin domain containing 1 Plasma Membrane other down 0.0001 -0.8618 ILMN_1710326 CLDND1 down 0.0008 -0.4139 11753241_s_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other down 0 -1.2044 ILMN_1663142 CLEC12A updown 0.0122 0 0.0316 -0.6278 11762101_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other down 0.001 -0.6634 11729479_a_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other down 0.0012 -0.7179 11732904_a_at CLEC1B C-type lectin domain family 1, member B Plasma Membrane transmembrane receptor down 0.0265 -0.512 ILMN_1745103 CLEC1B updown 0.0118 0.0144 0.0667 -0.3163 CLEC1B 21728173 CLEC1B is expressed in myeloid cells and acts as a SYK-coupled C-type lectin receptor (CLR) able to modulate Toll-like receptor (TLR) signaling and inflammatory responses. ( Demonstrated in murine model) 11728489_a_at CLEC4A C-type lectin domain family 4, member A Plasma Membrane transmembrane receptor down 0.0249 -0.6389 ILMN_1709204 CLEC4A down 0.001 -0.2746 11731993_at CLECL1 C-type lectin-like 1 Plasma Membrane other down 0.0012 -0.6715 ILMN_1782729 CLECL1 down 0 -0.4404 11724885_at CLIC3 chloride intracellular channel 3 Nucleus ion channel up 0.0274 0.6799 ILMN_1796423 CLIC3 updown 0.0003 0.0104 0.302 -0.2263 11716325_a_at CLK1 CDC-like kinase 1 Nucleus kinase down 0.0429 -0.5971 ILMN_1679727 CLK1 updown 0.049 0 0.1726 -0.7209 11726514_a_at CLK4 CDC-like kinase 4 Nucleus kinase down 0.0035 -0.8544 ILMN_1695853 CLK4 down 0.0002 -0.427 11726515_a_at CLK4 CDC-like kinase 4 Nucleus kinase down 0.0146 -0.7412 11726516_s_at CLK4 CDC-like kinase 4 Nucleus kinase down 0.0438 -0.6009 11748024_a_at CLK4 CDC-like kinase 4 Nucleus kinase down 0.0444 -0.5729 11729784_a_at CMTM2 CKLF-like MARVEL transmembrane domain containing 2 Extracellular Space cytokine down 0.0165 -0.7271 ILMN_1799030 CMTM2 down 0 -0.7514 11728036_a_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.0247 0.6446 ILMN_1775373 CMTM5 up 0.0239 0.3469 11753465_a_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.0257 0.6265 11728037_x_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.0353 0.5571 11755746_s_at CNIH4 cornichon homolog 4 (Drosophila) Plasma Membrane other down 0.0003 -0.8455 ILMN_1714759 CNIH4 down 0 -0.5636 11758808_a_at CNIH4 cornichon homolog 4 (Drosophila) Plasma Membrane other down 0.0485 -0.5415 11734956_a_at CNTNAP2 contactin associated protein-like 2 Plasma Membrane other down 0.0002 -0.7122 ILMN_1690223 CNTNAP2 updown 0.0136 0 -0.2106 -0.5954 11743352_s_at COBLL1 COBL-like 1 Extracellular Space other down 0.0362 -0.5814 ILMN_1761260 COBLL1 down 0.0001 -0.4813 11724049_a_at COG6 component of oligomeric golgi complex 6 Cytoplasm transporter down 0.0053 -0.7029 ILMN_1779530 COG6 down 0.0178 -0.2999 11743060_s_at COMMD10 COMM domain containing 10 unknown other down 0.0017 -0.793 ILMN_1766505 COMMD10 down 0.0093 -0.2416 11743059_at COMMD10 COMM domain containing 10 unknown other down 0.0169 -0.6241 11733495_a_at COMMD6 COMM domain containing 6 unknown other down 0 -1.2802 ILMN_1777378 COMMD6 down 0 -0.3636 11756875_x_at COMMD6 COMM domain containing 6 unknown other down 0 -1.1133 11733496_x_at COMMD6 COMM domain containing 6 unknown other down 0 -1.1327 11753841_x_at COMMD6 COMM domain containing 6 unknown other down 0 -1.1739 11720069_s_at COMMD8 COMM domain containing 8 unknown other down 0 -1.2256 ILMN_1765644 COMMD8 down 0 -0.3996 11732141_a_at COX16 COX16 cytochrome c oxidase assembly homolog (S. cerevisiae) Cytoplasm other down 0.0003 -0.7931 ILMN_1706305 COX16 down 0 -0.6018 11739459_a_at COX20 COX20 Cox2 chaperone homolog (S. cerevisiae) Cytoplasm other down 0.018 -0.6752 ILMN_1808584 COX20 down 0.0028 -0.2819 11717634_a_at COX6C cytochrome c oxidase subunit VIc Cytoplasm enzyme down 0.0001 -0.8185 ILMN_1654151 COX6C down 0.0002 -0.4025 11754444_x_at COX6C cytochrome c oxidase subunit VIc Cytoplasm enzyme down 0.0004 -0.7344 11753849_a_at COX7A2 cytochrome c oxidase subunit VIIa polypeptide 2 (liver) Cytoplasm enzyme down 0.0024 -0.6861 ILMN_1701293 COX7A2 down 0 -0.8663 11753850_x_at COX7A2 cytochrome c oxidase subunit VIIa polypeptide 2 (liver) Cytoplasm enzyme down 0.0031 -0.6935 11753892_x_at COX7A2 cytochrome c oxidase subunit VIIa polypeptide 2 (liver) Cytoplasm enzyme down 0.0442 -0.58 11715349_a_at COX7C cytochrome c oxidase subunit VIIc Cytoplasm enzyme down 0 -1.1612 ILMN_1798189 COX7C updown 0.0024 0 -0.2143 -1.2619 11735847_a_at CPA5 carboxypeptidase A5 Extracellular Space peptidase up 0.0346 0.055 ILMN_1791530 CPA5 up 0.0102 -0.0176 11726485_at CPED1 cadherin-like and PC-esterase domain containing 1 Cytoplasm other down 0.0015 -0.7824 ILMN_1677038 CPED1 down 0.0169 -0.3519 11739823_a_at CPNE8 copine VIII unknown other down 0.0324 -0.7498 ILMN_1722294 CPNE8 down 0.0169 -0.3244 11721433_a_at CRBN cereblon Cytoplasm enzyme down 0.0041 -0.7859 ILMN_1668582 CRBN down 0.0001 -0.4015 11739552_a_at CREB5 cAMP responsive element binding protein 5 Nucleus transcription regulator down 0.0439 -0.4351 ILMN_1731714 CREB5 updown 0.0042 0.0005 0.2696 -0.4618 11730761_s_at CRIPT cysteine-rich PDZ-binding protein Cytoplasm other down 0.0256 -0.4922 ILMN_1813256 CRIPT down 0.0008 -0.3752 11730759_s_at CRIPT cysteine-rich PDZ-binding protein Cytoplasm other down 0.0443 -0.6465 11726334_s_at CRLS1 cardiolipin synthase 1 Cytoplasm enzyme down 0.0091 -0.727 ILMN_1737685 CRLS1 down 0.0051 -0.3925 11729632_a_at CSDA cold shock domain protein A Nucleus transcription regulator up 0.0334 0.643 ILMN_1782788 CSDA up 0 0.6856 11719480_a_at CSTA cystatin A (stefin A) Cytoplasm other down 0 -1.3833 ILMN_1669888 CSTA down 0.0158 -0.2684 11757500_a_at CTDSPL CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase-likeNucleus other up 0.0003 0.9031 ILMN_1683444 CTDSPL up 0.0003 0.5263 11746740_a_at CTTN cortactin Plasma Membrane other up 0 0.9471 ILMN_1744912 CTTN up 0.0001 0.514 11748448_a_at CTTN cortactin Plasma Membrane other up 0.0004 0.8577 11722013_at CWC15 CWC15 spliceosome-associated protein homolog (S. cerevisiae) Nucleus other down 0.0011 -0.8896 ILMN_1713482 CWC15 down 0.0138 -0.3439 11720298_at CXCL10 chemokine (C-X-C motif) ligand 10 Extracellular Space cytokine MDX-1100 up 0 1.069 ILMN_1791759 CXCL10 up 0 0.1937 CXCL10 21518789 CXCL10 concentration in blood increases during neonatal polymicrobial sepsis, and the blockade of CXCL10 not only worsens recruitment and phagocytic function of macrophages, but also the survival of neonatal mice. (Demonstrated in murine model) 11720409_s_at CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide 1 Cytoplasm enzyme down 0.0001 -0.9665 ILMN_1693338 CYP1B1 down 0.0042 -0.235 21124994 CXCL10 exert direct antimicrobial effects in vitro against Bacillus anthracis spore and bacilli in a receptor-independent manner and contributes to pulmonary innate immunity. (Demonstrated in murine model) 11720411_s_at CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide 1 Cytoplasm enzyme down 0.0002 -0.9171 11720410_s_at CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide 1 Cytoplasm enzyme down 0.0045 -0.3825 20406818 DDX58 (RIG-I) phosphorylation on serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction. 11733297_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.0442 -0.23 ILMN_1736190 CYP4F3 down 0.0027 -0.2357 15208624 DDX58 (RIG-I) is a cytoplasmic RNA helicase that functions as an intracellular sensor of dsRNA leading to the induction of Interferon (IFN) production independently of TLR signalling. 11716580_s_at CYSTM1 cysteine-rich transmembrane module containing 1 unknown other down 0.0003 -0.5334 ILMN_1761566 CYSTM1 updown 0.0053 0 0.2222 -0.5806 18948594 DDX58 (RIG-I) first and second caspase recruitment domains (CARDs) have distinct roles in TRIM25-mediated RIG-I ubiquitination, which leads to initiation of an antiviral signalling cascade. 11716579_a_at CYSTM1 cysteine-rich transmembrane module containing 1 unknown other down 0.0008 -0.4122 19074283 DDX58 serves as a critical link between TLR3 and type-II-IFN signalling pathways in innate antiviral immune responses. 11718039_at DCAF12 DDB1 and CUL4 associated factor 12 Cytoplasm other up 0.0003 0.8084 ILMN_1786328 DCAF12 up 0.001 0.3859 19683681 DDX58 plays an essential role in Toll-like receptor (TLR)-stimulated phagocytosis, demonstrating that DDX58 plays a role not only in antiviral responses but in antibacterial responses as well. 11743002_at DCTN6 dynactin 6 Cytoplasm enzyme down 0.0027 -0.8276 ILMN_1744059 DCTN6 down 0.0001 -0.406 18523264 DDX58 plays a key role in the expression of TNF-alpha in macrophages in response to LPS stimulation, mainly for the late phase LPS-induced expression of TNF-alpha. 11733149_a_at DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 Cytoplasm enzyme up 0.0455 0.3735 ILMN_1797001 DDX58 updown 0.0001 0.0159 0.4896 -0.0496 DDX58 19915568 DDX58 is a sensor able to activate the inflammasome in response to certain RNA viruses by binding to the adaptor PYCARD to trigger the caspase-1 (CASP1)-dependent inflammasome activation and IL-1-beta production. 11721438_s_at DEFA1 (includes others) defensin, alpha 1 Cytoplasm other updown 0.0221 0 0.1178 -0.7607 ILMN_1679357 DEFA1 (includes others) updown 0 0 0.4327 -0.5926 20403326 DDX58 binds specifically to K63-polyubiquitin chains through its tandem caspase recruitment domains (CARDs) that act as a ubiquitin sensor in a manner that depends on RNA and ATP, demonstrate that un-anchored K63-polyubiquitin chains are signalling molecu ILMN_1725661 DEFA1 (includes others) updown 0 0 0.3763 -0.5914 22912779 Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse) 11719707_a_at DHRS13 dehydrogenase/reductase (SDR family) member 13 unknown enzyme down 0.044 -0.5804 ILMN_1790781 DHRS13 updown 0.0001 0.0357 0.5744 -0.2972 20511549 DDX58 innate immune response to viral infection of human cells is modified by a functional polymorphism in the RIG-I caspase recruitment domain (CARD). 11721897_a_at DHX58 DEXH (Asp-Glu-X-His) box polypeptide 58 Cytoplasm enzyme up 0.009 0.454 ILMN_1678422 DHX58 up 0.0001 0.2816 DHX58 19936053 DDX58 (RIG-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response. (Demonstrated in murine model) 11749497_a_at DHX58 DEXH (Asp-Glu-X-His) box polypeptide 58 Cytoplasm enzyme up 0.0108 0.4358 21690088 DDX58 and NOD2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. DDX58 negatively regulates ligand-induced NFkB signalling mediated by NOD2, and conversely, NOD2 negatively regulates type I interferon i 11764037_s_at DNAJA1 DnaJ (Hsp40) homolog, subfamily A, member 1 Nucleus other down 0.0496 -0.4292 ILMN_1672496 DNAJA1 down 0.0005 -0.3685 21695051 DDX58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus to suppress viral replication. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of DDX58. 11743050_a_at DNAJC15 DnaJ (Hsp40) homolog, subfamily C, member 15 Cytoplasm other down 0.0435 -0.5491 ILMN_1812666 DNAJC15 down 0.0016 -0.3668 22072774 DDX58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling. (Demonstrated in mice) 11733037_a_at DPH3 DPH3, KTI11 homolog (S. cerevisiae) Cytoplasm other down 0.0349 -0.6639 ILMN_1679912 DPH3 down 0.0338 -0.2588 17190814 DHX58 (LGP2) helicase is related to DDX58 (RIG-I) and IFIH1 (MDA5) but lacks caspase activation and recruitment domains (CARDs), and functions as a negative regulator of innate host defence. 11754523_a_at DPM1 dolichyl-phosphate mannosyltransferase polypeptide 1, catalytic subunit Cytoplasm enzyme down 0.0056 -0.7112 ILMN_1658992 DPM1 down 0.0009 -0.3981 16210631 DHX58 lacks the caspase recruitment domain (CARD) homology and functions as a negative regulator by interfering with the recognition of viral RNA by DDX58 (RIG-I) and IFIH1 (MDA5). 11719154_a_at DRAM1 DNA-damage regulated autophagy modulator 1 Cytoplasm other down 0.0318 -0.6671 ILMN_1669376 DRAM1 down 0.0213 -0.3107 16116171 DHX58 functions as a negative regulator of antiviral innate immunity by interfering with the recognition of viral RNA by DDX58 (RIG-I) and IFIH1 (MDA5). 11717563_a_at DTX3L deltex 3-like (Drosophila) Cytoplasm enzyme up 0.0417 0.4839 ILMN_1784380 DTX3L up 0.0012 0.313 11719373_at DYNLT3 dynein, light chain, Tctex-type 3 Cytoplasm other down 0.0008 -0.9276 ILMN_1681890 DYNLT3 down 0.0002 -0.4043 11747936_a_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other updown 0.0007 0.0087 1.0826 -0.4214 ILMN_1810420 DYSF updown 0 0.0005 0.8876 -0.2971 11719223_a_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other updown 0.0012 0.0129 0.9941 -0.3991 11745836_x_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other updown 0.0042 0.0132 0.9314 -0.4019 12954221 EIF2AK2 is a protein kinase that is regulated by RNA and is an important mediator of the antiviral and anti proliferative actions of interferon (IFN). 11737718_a_at EEF1E1 eukaryotic translation elongation factor 1 epsilon 1 Cytoplasm translation regulator down 0.0001 -0.8907 ILMN_1725105 EEF1E1 down 0.0006 -0.4266 12954221 EIF2AK2 binds both SP1 and SP3 but only SP3 functions as part of the interferon-inducible complex with ISGF-3 proteins, consisting of STAT1, STAT2, and IRF9. 11743582_a_at EEF1E1 eukaryotic translation elongation factor 1 epsilon 1 Cytoplasm translation regulator down 0.0011 -0.7941 19028691 EIF2AK2 enhances the induction of interferon-beta and apoptosis mediated by cytoplasmic RNA sensors where in addition to MAVS and IRF3 but not TRIF, it is required for maximal type I IFN-beta induction and the induction of apoptosis by both transfected T7 11733851_at EIF2A eukaryotic translation initiation factor 2A, 65kDa Cytoplasm translation regulator down 0.0058 -0.3155 ILMN_1733305 EIF2A down 0.0123 -0.2849 20485506 EIF2AK2 is used by hepatitis C virus to restrain its ability to induce IFN through the RIG-I/MAVS pathway. 11730991_a_at EIF2AK2 eukaryotic translation initiation factor 2-alpha kinase 2 Cytoplasm kinase up 0.0064 0.3777 ILMN_1706502 EIF2AK2 updown 0.0024 0 0.2123 -0.5443 EIF2AK2 23372823 EIF2AK2 binds to dsRNA to inhibit IFN induction triggered by dengue virus. 11735193_x_at EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 Plasma Membrane G-protein coupled receptor down 0.0221 -0.4553 ILMN_1800524 EMR2 updown 0.002 0.0115 0.2748 -0.2688 22912779 Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse) 11746366_x_at EPB41 erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked) Plasma Membrane other up 0.0004 0.8316 ILMN_1667408 EPB41 up 0 0.6177 23115300 Herpes simplex virus evades antiviral host defence by interacting with EIF2AK2 (PKR) to inhibit autophagy. 11746365_a_at EPB41 erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked) Plasma Membrane other up 0.0017 0.6913 23236554 Bacterial dsRNA or poly(I:C) induces tyrosine phosphorylation of PKR activation by JAK kinases. 11725009_a_at EPB42 erythrocyte membrane protein band 4.2 Plasma Membrane transporter up 0 0.8273 ILMN_1814397 EPB42 up 0 0.4037 11741343_a_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0.0002 0.8124 ILMN_1671686 EPB49 up 0.0015 0.3023 11747661_x_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0.0001 0.8028 11747660_a_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0.0002 0.836 11741344_x_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0.0004 0.7535 11724319_x_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0.0017 0.5939 11726219_x_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0.0032 0.6394 11731181_a_at EPSTI1 epithelial stromal interaction 1 (breast) unknown other updown 0.0005 0.0244 0.7027 -0.6311 ILMN_1688566 EPSTI1 updown 0 0 0.3984 -0.5428 11722573_a_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase down 0 -0.9031 ILMN_1743145 ERAP2 down 0 -0.4429 11754048_a_at ERH enhancer of rudimentary homolog (Drosophila) Nucleus other down 0.002 -0.8633 ILMN_1781795 ERH down 0 -0.37 11762512_a_at ERICH1 glutamate-rich 1 unknown other down 0.0081 -0.5022 ILMN_1904238 ERICH1 down 0.0031 -0.3814 11726321_a_at ERO1L ERO1-like (S. cerevisiae) Cytoplasm enzyme down 0.0498 -0.4604 ILMN_1744963 ERO1L down 0.0235 -0.3301 11733841_a_at EVI2A ecotropic viral integration site 2A Plasma Membrane transmembrane receptor down 0 -1.2264 ILMN_1733579 EVI2A down 0 -0.792 11723554_at F5 coagulation factor V (proaccelerin, labile factor) Plasma Membrane enzyme drotrecogin alfa, antithrombinup alfa 0.0016 0.6197 ILMN_1709233 F5 up 0.0248 0.3359 11746669_a_at FAM118A family with sequence similarity 118, member A unknown other down 0 -0.6366 ILMN_1809147 FAM118A down 0 -0.3699 11720023_a_at FAM118A family with sequence similarity 118, member A unknown other down 0.0001 -0.4308 11755895_a_at FAM129A family with sequence similarity 129, member A Cytoplasm other down 0.0069 -0.439 ILMN_1810725 FAM129A updown 0.0015 0.0005 0.3626 -0.2747 ILMN_1667966 FAM129A updown 0.0144 0.0046 0.2603 -0.308 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other down 0.0001 -0.8647 ILMN_1687213 FAM167A down 0.0054 -0.2952 11739379_a_at FAM198B family with sequence similarity 198, member B Cytoplasm other down 0.0133 -0.5481 ILMN_1761941 FAM198B down 0 -0.7112 11757534_s_at FAM198B family with sequence similarity 198, member B Cytoplasm other down 0.0133 -0.5703 11741223_s_at FAM198B family with sequence similarity 198, member B Cytoplasm other down 0.0174 -0.6092 11743608_s_at FAM3C family with sequence similarity 3, member C Extracellular Space cytokine down 0.0104 -0.7905 ILMN_1777261 FAM3C down 0.002 -0.3323 11742232_s_at FAM3C family with sequence similarity 3, member C Extracellular Space cytokine down 0.0108 -0.7358 11748094_a_at FAM3C family with sequence similarity 3, member C Extracellular Space cytokine down 0.0377 -0.6353 11739340_at FAM46C family with sequence similarity 46, member C Extracellular Space other up 0.0006 0.8004 ILMN_1713266 FAM46C updown 0.0008 0.0335 0.3678 -0.2769 11725847_s_at FAM76B family with sequence similarity 76, member B unknown other down 0.0043 -0.8638 ILMN_1732614 FAM76B down 0.0046 -0.3995 11742889_at FBXO6 F-box protein 6 Cytoplasm enzyme up 0.0048 0.6728 ILMN_1701455 FBXO6 up 0.0001 0.5009 11724171_a_at FCHO2 FCH domain only 2 Cytoplasm other down 0.0103 -0.6931 ILMN_1670322 FCHO2 down 0.0045 -0.2259 11746880_x_at FLNA filamin A, alpha Cytoplasm other up 0.0433 0.7616 ILMN_1687335 FLNA up 0.0047 0.3567 11744141_x_at FOLR3 folate receptor 3 (gamma) Extracellular Space other down 0 -1.3695 ILMN_1730454 FOLR3 updown 0.0212 0 -0.3355 -0.79 11744140_a_at FOLR3 folate receptor 3 (gamma) Extracellular Space other down 0 -1.0543 11730666_at FOXP1 forkhead box P1 Nucleus transcription regulator up 0.0002 0.7444 ILMN_1768248 FOXP1 up 0.0012 0.4994 11745309_a_at FRMD3 FERM domain containing 3 unknown other up 0.0133 0.6759 ILMN_1698725 FRMD3 up 0.0008 0.4637 11750746_a_at FRMD3 FERM domain containing 3 unknown other up 0.0238 0.5392 11752486_a_at G6PD glucose-6-phosphate dehydrogenase Cytoplasm enzyme up 0.0313 0.7074 ILMN_1697559 G6PD up 0.0005 0.3568 11716293_x_at G6PD glucose-6-phosphate dehydrogenase Cytoplasm enzyme up 0.0462 0.6262 11731814_at GATA1 GATA binding protein 1 (globin transcription factor 1) Nucleus transcription regulator up 0.0003 0.8174 ILMN_1797251 GATA1 up 0.034 0.1983 11731813_a_at GATA1 GATA binding protein 1 (globin transcription factor 1) Nucleus transcription regulator up 0.0031 0.795 11753147_a_at GATA1 GATA binding protein 1 (globin transcription factor 1) Nucleus transcription regulator up 0.0103 0.6732 11726329_x_at GBP1 guanylate binding protein 1, interferon-inducible Cytoplasm enzyme up 0.0058 0.635 ILMN_1701114 GBP1 updown 0.0001 0.0048 0.2579 -0.2816 11752931_x_at GBP1 guanylate binding protein 1, interferon-inducible Cytoplasm enzyme up 0.0066 0.6109 11749773_x_at GBP1 guanylate binding protein 1, interferon-inducible Cytoplasm enzyme up 0.0128 0.467 11752930_a_at GBP1 guanylate binding protein 1, interferon-inducible Cytoplasm enzyme up 0.013 0.4996 11726328_x_at GBP1 guanylate binding protein 1, interferon-inducible Cytoplasm enzyme up 0.0479 0.538 11733950_at GBP4 guanylate binding protein 4 Cytoplasm enzyme up 0.006 0.6338 ILMN_1771385 GBP4 up 0 0.4119 11733952_at GBP4 guanylate binding protein 4 Cytoplasm enzyme up 0.0085 0.5348 11733953_x_at GBP4 guanylate binding protein 4 Cytoplasm enzyme up 0.0087 0.5307 11733951_at GBP4 guanylate binding protein 4 Cytoplasm enzyme up 0.0267 0.4982 11749595_a_at GBP4 guanylate binding protein 4 Cytoplasm enzyme up 0.0299 0.5969 11736092_at GCA grancalcin, EF-hand calcium binding protein Cytoplasm other down 0.0017 -0.8006 ILMN_1800602 GCA down 0.0003 -0.3875 11728937_at GFRA2 GDNF family receptor alpha 2 Plasma Membrane transmembrane receptor up 0.042 0.4861 ILMN_1656300 GFRA2 up 0.0134 0.2639 11743513_a_at GINS2 GINS complex subunit 2 (Psf2 homolog) Nucleus other down 0.0011 -0.5657 ILMN_1809590 GINS2 down 0 -0.4443 11732432_a_at GK glycerol kinase Cytoplasm kinase down 0.0081 -0.5395 ILMN_1725471 GK updown 0.0369 0.0004 0.1794 -0.3423 11734201_s_at GK glycerol kinase Cytoplasm kinase down 0.0129 -0.6935 11750720_s_at GK glycerol kinase Cytoplasm kinase down 0.0386 -0.5857 11747441_a_at GLRX glutaredoxin (thioltransferase) Cytoplasm enzyme down 0 -0.9413 ILMN_1737308 GLRX down 0.0003 -0.393 GLRX 21078302 GLRX (GRX-1), a degluationylation enzyme, activates TRAF6 and is responsible for IL1R / TLR-dependent induction of NFkB pathway. 11718048_a_at GLRX glutaredoxin (thioltransferase) Cytoplasm enzyme down 0 -0.8887 11724167_s_at GLT25D2 glycosyltransferase 25 domain containing 2 unknown other down 0.0105 -0.7473 ILMN_1736742 GLT25D2 down 0.0275 -0.1883 11724166_a_at GLT25D2 glycosyltransferase 25 domain containing 2 unknown other down 0.0112 -0.5939 11720202_at GMPR guanosine monophosphate reductase Cytoplasm enzyme up 0.0026 0.645 ILMN_1729487 GMPR up 0 0.5692 11722379_at GNG11 guanine nucleotide binding protein (G protein), gamma 11 Plasma Membrane enzyme down 0.0349 -0.4672 ILMN_1782419 GNG11 down 0.0036 -0.4521 11749333_a_at GNL3 guanine nucleotide binding protein-like 3 (nucleolar) Nucleus other down 0.0098 -0.8035 ILMN_1806106 GNL3 down 0.0067 -0.2627 11763755_a_at GNLY granulysin Cytoplasm other down 0 -1.208 ILMN_1708779 GNLY down 0 -0.5826 11763756_x_at GNLY granulysin Cytoplasm other down 0.0006 -0.8048 11756632_a_at GNLY granulysin Cytoplasm other down 0.0009 -0.9578 11763715_a_at GNLY granulysin Cytoplasm other down 0.0162 -0.7876 11751857_a_at GNLY granulysin Cytoplasm other down 0.021 -0.7817 11762571_a_at GNPDA2 glucosamine-6-phosphate deaminase 2 unknown enzyme down 0.0109 -0.8067 ILMN_1691567 GNPDA2 down 0.0008 -0.3733 11721866_a_at GNPDA2 glucosamine-6-phosphate deaminase 2 unknown enzyme down 0.0294 -0.6873 11739977_at GPR180 G protein-coupled receptor 180 unknown other down 0.0101 -0.672 ILMN_1738712 GPR180 down 0.0367 -0.3133 11758555_s_at GPR183 G protein-coupled receptor 183 Plasma Membrane G-protein coupled receptor down 0.0493 -0.5062 ILMN_1798706 GPR183 down 0.0054 -0.3423 11731669_at GPR65 G protein-coupled receptor 65 Plasma Membrane G-protein coupled receptor down 0.0008 -0.8215 ILMN_1734740 GPR65 down 0.0043 -0.4246 11725655_at GTF2H5 general transcription factor IIH, polypeptide 5 Nucleus other down 0.0049 -0.6443 ILMN_1739497 GTF2H5 down 0.0457 -0.2315 11745557_x_at GYPB glycophorin B (MNS blood group) Plasma Membrane other up 0.0009 0.7334 ILMN_1683093 GYPB up 0.0034 0.3683 11753662_x_at GYPB glycophorin B (MNS blood group) Plasma Membrane other up 0.0025 0.6588 11745299_x_at GYPB glycophorin B (MNS blood group) Plasma Membrane other up 0.003 0.7963 11753827_x_at GYPB glycophorin B (MNS blood group) Plasma Membrane other up 0.0103 0.5413 11755052_s_at GYPE glycophorin E (MNS blood group) Plasma Membrane other up 0.0201 0.5397 ILMN_1695187 GYPE updown 0 0.0126 0.5863 -0.1894 11720496_at GZMA granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3) Cytoplasm peptidase down 0.0014 -0.8262 ILMN_1779324 GZMA down 0 -0.7277 11728125_a_at GZMH granzyme H (cathepsin G-like 2, protein h-CCPX) Cytoplasm peptidase down 0.0187 -0.8209 ILMN_1731233 GZMH updown 0.004 0 0.0349 -0.5305 11725439_at HBD hemoglobin, delta Cytoplasm transporter up 0.0169 0.5016 ILMN_1815527 HBD up 0.0486 0.2402 11724835_s_at HCAR3 hydroxycarboxylic acid receptor 3 Plasma Membrane G-protein coupled receptor down 0.0118 -0.5431 ILMN_1677693 HCAR3 updown 0.0264 0.0029 0.2726 -0.3857 11722615_s_at HCAR3 hydroxycarboxylic acid receptor 3 Plasma Membrane G-protein coupled receptor down 0.0316 -0.532 11755386_a_at HDC histidine decarboxylase Cytoplasm enzyme updown 0.0163 0.0232 0.5401 -0.5949 ILMN_1792323 HDC updown 0 0.0034 0.6335 -0.0142 11755374_a_at HERC5 HECT and RLD domain containing E3 ubiquitin protein ligase 5 Cytoplasm enzyme updown 0 0.0003 0.589 -0.6609 ILMN_1729749 HERC5 updown 0 0 0.4648 -0.5177 HERC5 20308324 HERC5 positively regulates the innate antiviral responses by sustaining IRF3 activation via a novel post-translational modification, ISGylation. 11718201_at HEY1 hairy/enhancer-of-split related with YRPW motif 1 Nucleus transcription regulator up 0.006 0.0821 ILMN_1788203 HEY1 up 0.0299 0.2492 11753759_x_at HINT1 histidine triad nucleotide binding protein 1 Nucleus enzyme down 0 -0.8501 ILMN_1807710 HINT1 updown 0.0029 0 0.135 -1.1688 Diabetes Page 88 of 111

200093_PM_s_at HINT1 histidine triad nucleotide binding protein 1 Nucleus enzyme down 0.0006 -0.8156 11741813_s_at HINT1 histidine triad nucleotide binding protein 1 Nucleus enzyme down 0.0012 -0.8383 11757319_x_at HINT1 histidine triad nucleotide binding protein 1 Nucleus enzyme down 0.0019 -0.7873 11741814_x_at HINT1 histidine triad nucleotide binding protein 1 Nucleus enzyme down 0.0019 -0.7729 11757222_at HINT1 histidine triad nucleotide binding protein 1 Nucleus enzyme down 0.0305 -0.7358 11719406_a_at HIPK2 homeodomain interacting protein kinase 2 Nucleus kinase up 0.0398 0.5173 ILMN_1687440 HIPK2 up 0.0157 0.2293 11736915_at HIST1H1D histone cluster 1, H1d Nucleus other down 0.0065 -0.2852 ILMN_1749789 HIST1H1D down 0.012 -0.2476 11731694_s_at HIST1H2AB/HIST1H2AE histone cluster 1, H2ae Nucleus other down 0.0142 -0.5815 ILMN_1756849 HIST1H2AB/HIST1H2AE down 0.0003 -0.2956 11731693_at HIST1H2AB/HIST1H2AE histone cluster 1, H2ae Nucleus other down 0.0406 -0.6182 11738783_at HIST1H3A (includes others)histone cluster 1, H3a Nucleus other down 0 -0.7707 ILMN_1712184 HIST1H3A (includes others)down 0.0135 -0.236 11759760_s_at HIST2H2BE (includes others)histone cluster 2, H2be Nucleus other down 0.0044 -0.742 ILMN_1732071 HIST2H2BE (includes others)down 0.0319 -0.2552 11734797_x_at HIST2H2BE (includes others)histone cluster 2, H2be Nucleus other down 0.0375 -0.5235 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other updown 0.0004 0.0006 -0.0152 -0.2252 ILMN_1721113 HLA-C updown 0 0.0093 0.1686 -0.0097 21871094 HMGB1 has a pathogenic role in arthritis, where in complex with lipopolysaccharide, IL1A or IL1B, HMGB1 boosts the production of proinflammatory cytokines and MMP3 as demonstrated in synovial fibroblasts from rheumatoid arthritis and osteoarthritis patien 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor down 0 -0.2096 ILMN_1749070 HLA-DPB1 down 0.0449 -0.1237 21389264 HMGB1 is found in high concentrations within neutrophil extracellular traps (NETs). HMGB1 is a neutrophil protein that facilitates the uptake and recognition of mammalian DNA by plasmacytoid dendritic cells, and may play a role in Systemic Lupus Erthermat 11760878_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor down 0.0021 -0.1416 21372296 HMGB1 is an endogenous TLR4 ligand in macrophages and its release in wounds initiates TLR4-dependent responses that contribute to neovascularization. (Demonstrated in murine model) 11750528_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor down 0.0036 -0.1573 ILMN_1791534 HLA-DQA1 down 0.0044 -0.3606 21860212 HMGB1 plays a key regulatory role in polymorphonuclear neutrophil (PMN) recruitment to inflammatory tissues. Low concentrations of HMGB1 (50-100 ng/ml) reduce baseline PMN migration as well as formyl-methionyl-leucyl-phenylalanine- and IL8-induced PMN che 11724799_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor down 0.0164 -0.0446 ILMN_1808405 HLA-DQA1 down 0.0061 -0.449 19914413 HMGB1 activates innate immunity mechanisms as a complex with DNA, lipids and/or pro-inflammatory cytokines. 11739026_x_at HMGB1 high mobility group box 1 Nucleus transcription regulator down 0.0138 -0.7513 ILMN_1791466 HMGB1 down 0.0338 -0.1888 HMGB1 19890330 HMGB1 functions as universal sentinel for nucleic-acid-mediated innate immune responses. 11743687_s_at HMGB2 high mobility group box 2 Nucleus transcription regulator down 0.0153 -0.7607 ILMN_1654268 HMGB2 down 0 -0.4404 HMGB2 20419158 HMGB1 is an alarmin and a key mediator of natural killer (NK)-dendritic cell (DC) cross-talk and plays a pivotal role in the escape of Human Immunodeficiency Virus (HIV)-infected dendritic cells from TRAIL-mediated NK cell cytotoxicity during NK-DC cross- 11758089_s_at HMMR hyaluronan-mediated motility receptor (RHAMM) Plasma Membrane other down 0 -1.1634 ILMN_1781942 HMMR down 0.0046 -0.2355 22396017 Nuclear HMGB1 translocates to the cytoplasm in LPS-stimulated macrophages to potentiate inflammatory responses. (Demonstrated in mice) 11720141_a_at HMMR hyaluronan-mediated motility receptor (RHAMM) Plasma Membrane other down 0.0003 -0.5893 19890330 HMGB2 functions as a universal sentinel for nucleic-acid-mediated innate immune responses. 11727285_at HSF5 heat shock transcription factor family member 5 unknown other down 0.0098 -0.6736 ILMN_1680914 HSF5 down 0.0145 -0.3289 18950863 HSP90AA1 regulates the stability of transforming growth factor beta-activated kinase 1 (TAK1) in interleukin-1beta (IL1B)-induced cell signalling and IL1B-induced signalling by interacting with and maintaining the stability of TAK1, suggesting that HSP90A 11758308_s_at HSP90AA1 heat shock protein 90kDa alpha (cytosolic), class A member 1 Cytoplasm enzyme 17-dimethylaminoethylamino-17-demethoxygeldanamycin,down IPI-504,0.004 cisplatin -0.6021 ILMN_1691097 HSP90AA1 down 0 -0.3349 HSP90AA1 17420470 HSP90AA1 (HSP90) positively regulates NOD1 activation. 11732996_at HSP90AA1 heat shock protein 90kDa alpha (cytosolic), class A member 1 Cytoplasm enzyme 17-dimethylaminoethylamino-17-demethoxygeldanamycin,down IPI-504,0.011 cisplatin -0.6079 11727845_a_at HSPA14 heat shock 70kDa protein 14 Cytoplasm peptidase down 0.0494 -0.582 ILMN_1797318 HSPA14 down 0.0016 -0.3671 HSPA14 21730052 HSPA14 binds directly to TLR4 on dendritic cell surfaces and induces a robust Th1 response via the MAPK and NFkB signalling pathways. 11716351_s_at HSPE1 heat shock 10kDa protein 1 (chaperonin 10) Cytoplasm enzyme down 0.0258 -0.6602 ILMN_1803775 HSPE1 down 0.0003 -0.3587 11743168_at IDO1 indoleamine 2,3-dioxygenase 1 Cytoplasm enzyme up 0 0.9052 ILMN_1656310 IDO1 up 0.005 0.2579 IDO1 22355111 IDO1 limits innate and adaptive immunity to apoptotic self-antigens. IDO1-mediated inhibition of inflammation plays a key role in suppressing systemic autoimmune diseases. (Demonstrated in mice) 11719491_a_at IFI35 interferon-induced protein 35 Nucleus other up 0.0001 0.6767 ILMN_1745374 IFI35 up 0 0.6557 11719492_s_at IFI35 interferon-induced protein 35 Nucleus other up 0.0004 0.7121 11748003_a_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0006 0 0.6773 -1.0016 ILMN_1760062 IFI44 updown 0 0 0.3109 -0.6617 11760254_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0022 0.0003 0.4113 -0.4074 11719886_a_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0072 0.0006 0.5455 -0.6542 11760252_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0008 0.0012 0.5363 -0.4373 11746088_a_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0153 0.0027 0.487 -0.5808 11760253_x_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0009 0.0355 0.5086 -0.2913 11723236_at IFI44L interferon-induced protein 44-like unknown other updown 0.0002 0 0.2227 -0.7766 ILMN_1723912 IFI44L updown 0 0 0.5348 -0.2057 11723234_at IFI44L interferon-induced protein 44-like unknown other updown 0.0001 0.0016 0.2923 -0.5972 ILMN_1835092 IFI44L up 0.0422 0.2074 11723235_a_at IFI44L interferon-induced protein 44-like unknown other updown 0 0.0024 0.7256 -0.3516 15685448 IFI6 has a function as a cell survival protein by inhibiting mitochondrial-mediated apoptosis. 11718986_a_at IFI6 interferon, alpha-inducible protein 6 Cytoplasm other up 0.0032 0.4782 ILMN_1687384 IFI6 updown 0.0114 0.0001 0.2848 -0.3997 IFI6 20939681 IFI6 (G1P3) gene encodes a low molecular weight mitochondrial protein that stabilizes mitochondrial function and opposes apoptosis. 11756820_a_at IFIT1 interferon-induced protein with tetratricopeptide repeats 1 Cytoplasm other updown 0.0002 0 0.4896 -1.18 ILMN_1707695 IFIT1 updown 0 0 0.4786 -0.6399 IFIT1 20386592 IFIT1 expression activates the IFN response during C. pneumoniae infection, mediated by intracellular nucleotide-sensing pattern recognition receptors (PRRs), which operate through a mechanism dependent on the bacterial type III secretion system (T3SS). 11737280_at IFIT1B interferon-induced protein with tetratricopeptide repeats 1B Cytoplasm other up 0.0223 0.577 ILMN_1759155 IFIT1B up 0.0242 0.2377 22745654 IFIT1 is an innate immune network bottleneck with the ability to suppress induction of TLR4 response genes in LPS-stimulated macrophages. (Demonstrated in mice) 11721873_at IFIT2 interferon-induced protein with tetratricopeptide repeats 2 Cytoplasm other updown 0.0008 0.0011 0.3389 -0.669 ILMN_1739428 IFIT2 updown 0.0001 0.0003 0.1042 -0.5429 IFIT2 21642987 IFIT1 recognizes and directly binds to 5'-triphosphate RNA and functions as an innate inhibitor of viral replication and pathogenicity. (Demonstrated in murine model) 11726656_a_at IFIT5 interferon-induced protein with tetratricopeptide repeats 5 unknown other down 0.0097 -0.4728 ILMN_1696654 IFIT5 updown 0.043 0.0058 0.133 -0.3383 22065572 IFIT2 expression imparts anti-viral immunity to restrict West Nile virus infection and control viral pathogenesis. (Demonstrated in mice) 11715239_x_at IFITM3 interferon induced transmembrane protein 3 Plasma Membrane other updown 0 0 0.7182 -1.0382 ILMN_1805750 IFITM3 updown 0 0 0.7958 -1.2792 IFITM3 19108715 IFIT2 belongs to type 1 interferon response genes and is highly induced after stimulation with LPS and selectively affects LPS induced protein expression by regulation at different post-transcriptional levels. 11748152_a_at IFNGR1 interferon gamma receptor 1 Plasma Membrane transmembrane receptor interferon gamma-1bdown 0.0482 -0.6064 ILMN_1675939 IFNGR1 down 0.0003 -0.4391 IFNGR1 20601941 IFITM3 is post-translationally regulated by S-palmitoylation on membrane-proximal cysteines, which controls its clustering in membrane compartments and its antiviral activity against influenza virus. 11731440_a_at IFT57 intraflagellar transport 57 homolog (Chlamydomonas) Cytoplasm other down 0.0141 -0.794 ILMN_1811636 IFT57 down 0.0055 -0.4483 20064371 IFITM3 is an antiviral restriction factor that mediates cellular resistance to influenza A H1N1 virus, West Nile virus, and Dengue virus. 11741712_a_at IGF2BP2 insulin-like growth factor 2 mRNA binding protein 2 Cytoplasm translation regulator up 0.0005 0.6713 ILMN_1702447 IGF2BP2 updown 0 0.0261 0.6284 -0.2205 16785527 IFNGR1, along with IFNGR2, are the receptor subunits for IFN-gamma that upon ligand binding, translocate to the nucleus together with STAT1-alpha, and associate with IFN-gamma-activated sequence (GAS) elements at the promoter sites of IFN-gamma-activated 11757763_s_at IGF2BP2 insulin-like growth factor 2 mRNA binding protein 2 Cytoplasm translation regulator up 0.0035 0.7296 11716128_at IGF2R insulin-like growth factor 2 receptor Plasma Membrane transmembrane receptor up 0.0317 0.7145 ILMN_1807662 IGF2R up 0.0027 0.2866 22940097 IL18 secreted by inflammatory monocytes is critical for the differentiation of memory CD8(+) T and NK lymphocytes into antimicrobial effector cells. (Demonstrated in mice) 11759852_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0157 0.0044 0.382 -0.6935 ILMN_1908133 IGHG1 updown 0.0354 0 0.025 -0.4878 20195505 IL18 and IL1B are important pro-inflammatory cytokines that activates monocytes, macropages, and neutrophils, as well as induce the Th1 and Th17 adaptive cellular responses. 11760929_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0202 0.0114 0.3079 -0.6301 22426547 IL1B is an inflammatory cytokine that binds to its primary receptor, IL1R1, that then recruits the accessory protein IL1RAP to form a signalling-competent heterotrimeric complex. 11760819_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0178 0.0125 0.3789 -0.655 20620944 IL1B-producing conventional dendritic cells preserves and expands IL-22(+)AHR(+) immature human natural killer cells in the secondary lymphoid tissue. 11745244_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0388 0.0162 0.2893 -0.5692 21170027 IL1B acts as a growth factor for neutrophil progenitors and as a survival factor for mature neutrophils. In the absence of IKBKB, the IL1B production is enhanced and provides a compensatory mechanism for maintaining antibacterial defense when NFKB is inhi 11754032_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0296 0.0179 0.3234 -0.6499 21228274 IL1B secretion in macrophages is regulated by autophagy by two mechanisms; sequestering of pro-IL1B in autophagosome during TLR stimulation, and processing,secretion of IL1B in a NLRP3- and TRIF-dependent manner. 11750231_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0274 0.0183 0.3146 -0.5841 22158745 IL1B is an important component of the cellular network involving macrophages and epithelial cells, which facilitates IL8 chemokine expression and aids neutrophil recruitment during pneumococcal pneumonia. 11727092_x_at IL18 interleukin 18 (interferon-gamma-inducing factor) Extracellular Space cytokine down 0.025 -0.7368 ILMN_1778457 IL18 down 0.0447 -0.1709 IL18 20195505 IL1B is an important proinflammatory cytokine that activates monocytes, macropages, and neutrophils. IL1B processing during infection is a complex process in which the inflammasomes are only one of several activation mechanisms. 11732017_a_at IL18RAP interleukin 18 receptor accessory protein Plasma Membrane transmembrane receptor down 0.0235 -0.5821 ILMN_1721762 IL18RAP down 0 -0.5712 21602824 IL1B secretion is induced only during viable E. coli infection (as oppose to heat-killed E. coli or LPS); Viable bacteria specifically elicit cleavage of pro-IL1B. (Demonstrated in murine model) 11719916_at IL1B interleukin 1, beta Extracellular Space cytokine IL-1 trap, canakinumabdown 0.0057 -0.6477 ILMN_1775501 IL1B updown 0.0024 0 0.1985 -0.6413 IL1B 21628463 IL1B secretion is tightly regulated by the redox status in myeloid cells. TLR engagement in monocytes induces ROS generation followed by a sustained antioxidant response and efficient IL1B secretion. In macrophages, the antioxidant systems are in an upreg 11734541_a_at IL5RA interleukin 5 receptor, alpha Plasma Membrane transmembrane receptor up 0.0002 0.4905 ILMN_1756455 IL5RA up 0.037 0.1925 21270399 IL1B derived from alveolar macrophages is the critical mediator which induces chemokine production in non-hematopoietic cells in the lung, resulting in swift and robust recruitment of infection-controlling neutrophils into the airways. (Demonstrated in mu 11753566_a_at IL5RA interleukin 5 receptor, alpha Plasma Membrane transmembrane receptor up 0.001 0.5369 20401526 Mature IL1B production requires, in addition to the synthesis of pro-IL1B, cleavage of the precursor protein by the inflammatory CASP1 (Caspase-1) which is controlled within the NLRP3 inflammasome. 11730757_a_at IL6ST interleukin 6 signal transducer (gp130, oncostatin M receptor) Plasma Membrane transmembrane receptor up 0.029 0.7299 ILMN_1849013 IL6ST updown 0.0086 0.0026 0.3552 -0.3978 IL6ST 10829066 IL6ST (GP130) is a common cytokine receptor subunit that is preferentially bound by SOCS3 on its SHP2-binding site, suggesting that some of the negative regulatory roles previously attributed to the phosphatase SHP-2 might in fact be caused by the action 11718841_s_at IL8 interleukin 8 Extracellular Space cytokine down 0 -1.3078 ILMN_1666733 IL8 down 0.0006 -0.4034 IL8 17220369 IL8 is produced by airway epithelial cells in response to invading bacteria and mediates airway epithelial defence against bacterial infection via the DUOX1-TACE-TGF-alpha-EGFR signalling pathway. 11733144_s_at IMPA1 inositol(myo)-1(or 4)-monophosphatase 1 Cytoplasm phosphatase down 0.0035 -0.8257 ILMN_1758811 IMPA1 down 0.0096 -0.2837 21098228 IRAK3 is strongly expressed in resting alveolar macrophages and blunts TNF expression to protect the host from the injurious effect of bacterial-induced inflammation. The inhibitory function of IRAK3 is abolished when it is cleaved by CASP6, which allows 11728592_at IPO11 importin 11 Nucleus transporter down 0.0003 -0.8469 ILMN_1684746 IPO11 down 0.0085 -0.3798 20042589 IRAK3 is critical to preventing deleterious neutrophil-dependent lung injury during influenza infection of the respiratory tract. 11726895_a_at IRAK3 interleukin-1 receptor-associated kinase 3 Cytoplasm kinase down 0.0276 -0.5552 ILMN_1913678 IRAK3 down 0 -0.5858 IRAK3 22154382 IRAK3 dampens the innate immune response in airway epithelial cells by inhibiting TLR2 signalling in an IL13-dependent manner. ILMN_1661695 IRAK3 down 0.0001 -0.468 17982103 IRAK3 upregulation by lipopolysaccharide (LPS) is largely dependent on TNF-alpha and LPS tolerance in human endotoxemia models is associated with IRAK3 up-regulation. 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator updown 0 0.0024 0.1415 -0.0616 ILMN_1670576 IRF5 updown 0.0042 0.0004 0.1475 -0.0812 IRF5 17379480 IRAK3 selectively attenuates Pam3CSK4-induced MAPK14 (p38) activation through an IRAK1 independent and MKP1 dependent pathway. 11719292_a_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other down 0 -0.5925 ILMN_1665107 ITGB1BP1 down 0 -0.4591 19809574 IRAK3 is one of the negative regulators that contribute to the attenuation of NF-kappaB activation and it negatively regulates the alternative NF-kappaB pathway in a ligand-specific manner. 11719293_s_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other down 0.0002 -0.7061 14660668 IRAK3 induction and inhibition of kinase activity of IRAK1 are crucial to peptidoglycan-induced tolerance in macrophages. 11756857_a_at JAK2 Janus kinase 2 Cytoplasm kinase ruxolitinib down 0.0295 -0.3666 ILMN_1683178 JAK2 down 0.0401 -0.2855 JAK2 22492852 IRAK3 impairs host defence during pneumococcal pneumonia at the primary site of infection. (Demonstrated in mice) 11732641_a_at JKAMP JNK1/MAPK8-associated membrane protein Cytoplasm other down 0.0048 -0.6713 ILMN_1700276 JKAMP down 0.0043 -0.3782 12620219 IRAK3 is part of the interleukin-1 receptor-associated kinase (IRAK) family of proteins that mediate activation of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) pathways. 11730012_s_at KBTBD8 kelch repeat and BTB (POZ) domain containing 8 unknown other down 0 -1.1413 ILMN_1716272 KBTBD8 down 0.0087 -0.3846 12150927 IRAK3 regulates Toll-like receptor (TLR) signalling and innate immune homeostasis where IRAK3 is induced upon TLR stimulation and negatively regulates TLR signalling. 11732454_at KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 Plasma Membrane ion channel updown 0.0316 0.0017 0.5845 -0.537 ILMN_1675756 KCNJ15 updown 0.0016 0.001 0.2768 -0.4121 18332133 IRF5 is activated by both TBK1 and MYD88 to form a homodimer that binds to and activates transcription of type I interferon and inflammatory cytokine genes. 11732455_at KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 Plasma Membrane ion channel down 0.0434 -0.3511 12600985 IRF5 can act as both an activator and a repressor of interferon (IFN) gene induction dependent on the IRF-interacting partner, and may be a part of the regulatory network that ensures timely expression of the immediate early inflammatory genes. 11730465_at KCNJ2 potassium inwardly-rectifying channel, subfamily J, member 2 Plasma Membrane ion channel nicorandil, amiodaronedown 0.0125 -0.6786 ILMN_1780334 KCNJ2 down 0 -0.4915 22412986 Phosphorylation of IRF5 at ser451 and ser462 is the primary trigger of IRF5 function in nuclear accumulation, transcription and apoptosis. 11722627_at KIAA1033 KIAA1033 Cytoplasm other down 0.0012 -0.6594 ILMN_1782222 KIAA1033 down 0.0083 -0.2353 22218715 JAK2 functions downstream of TLR2-stimulation to induce the expression of the monocyte chemoattractant protein 1, CCL2. (Demonstrated in mice) 11722626_at KIAA1033 KIAA1033 Cytoplasm other down 0.0077 -0.7994 8041779 JAK2 and JAK1 tyrosine kinases physically associate with the gamma chain and beta chain of the interleukin 2 (IL-2) receptor , respectively, suggesting that regulation of the kinases may be linked to IL-2-induced signal transduction. 11720780_a_at KIAA1324 KIAA1324 Plasma Membrane other up 0 0.9477 ILMN_1771482 KIAA1324 updown 0 0.0155 0.6935 -0.2696 15121872 JAK2 binds to the majority of the known members of the cytokine family of receptors and ligand-receptor binding leads to activation of the associated JAK2 molecules, resulting in rapid autophosphorylation of multiple tyrosines within JAK2. Tyrosine 813 is 11760258_x_at KIAA1324 KIAA1324 Plasma Membrane other up 0.0005 0.7726 20393690 JAK2 inhibition prevents innate immune responses and rescues animals from sepsis by specifically preventing LPS-induced STAT3 tyrosine phosphorylation without affecting serine phosphorylation in macrophages and by preventing the activation of the canonica 11722881_at KIAA1468 KIAA1468 unknown other down 0.0083 -0.7024 ILMN_1798346 KIAA1468 down 0.0008 -0.4041 11758265_s_at KIAA1468 KIAA1468 unknown other down 0.0289 -0.6721 11734804_a_at KIF20B kinesin family member 20B Nucleus enzyme down 0.0017 -0.9175 ILMN_1712452 KIF20B down 0 -0.5192 11742301_x_at KIR2DL3 (includes others) killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 3 Plasma Membrane other up 0.0009 0.5959 ILMN_1667232 KIR2DL3 (includes others) updown 0 0.0284 0.3991 -0.1793 11730138_at KLF1 Kruppel-like factor 1 (erythroid) Nucleus transcription regulator up 0.0073 0.6922 ILMN_1707304 KLF1 up 0.0123 0.261 11728362_s_at KLHL28 kelch-like 28 (Drosophila) unknown other down 0.0078 -0.5725 ILMN_1693401 KLHL28 down 0.0368 -0.284 11742216_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0 -0.6889 ILMN_1799134 KLRD1 down 0 -0.606 11753534_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0001 -0.6643 ILMN_1797988 KLRD1 down 0.0016 -0.2951 11740451_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0006 -0.7771 11753484_x_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0011 -0.6886 11753535_x_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0015 -0.6623 11740452_x_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0049 -0.6279 11756590_a_at KMO kynurenine 3-monooxygenase (kynurenine 3-hydroxylase) Cytoplasm enzyme down 0.0112 -0.6345 ILMN_1730917 KMO down 0.0423 -0.2288 11726002_s_at KRCC1 lysine-rich coiled-coil 1 Extracellular Space other down 0 -0.9395 ILMN_1745620 KRCC1 down 0.037 -0.2741 11723952_at KRT1 keratin 1 Cytoplasm other up 0 0.4528 ILMN_1735712 KRT1 up 0 0.5561 11733718_x_at LAIR2 leukocyte-associated immunoglobulin-like receptor 2 Plasma Membrane other up 0.0152 0.5611 ILMN_1807491 LAIR2 updown 0.005 0.0124 0.3492 -0.0103 11718768_a_at LAMTOR3 late endosomal/lysosomal adaptor, MAPK and MTOR activator 3 Cytoplasm other down 0.001 -0.7705 ILMN_1659415 LAMTOR3 down 0 -0.6552 11721243_a_at LAP3 leucine aminopeptidase 3 Cytoplasm peptidase up 0.001 0.3474 ILMN_1683792 LAP3 up 0.0005 0.2557 11757634_a_at LCN2 lipocalin 2 Extracellular Space transporter updown 0.0002 0.0001 0.3314 -0.5558 ILMN_1692223 LCN2 updown 0.0008 0.0011 0.3469 -0.1934 11746636_a_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.006 0.5261 ILMN_1904481 LEF1 up 0.0008 0.3408 11747931_a_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.0061 0.5435 ILMN_1679185 LEF1 up 0.0052 0.4253 11747932_x_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.0341 0.4392 11731765_a_at LGALS12 lectin, galactoside-binding, soluble, 12 Extracellular Space other up 0.0115 0.5286 ILMN_1776283 LGALS12 up 0.0051 0.3229 11731798_a_at LGALS2 lectin, galactoside-binding, soluble, 2 Cytoplasm other down 0.0476 -0.3174 ILMN_1687306 LGALS2 updown 0.0023 0.0329 0.4283 -0.065 LGALS2 15356130 LGASL2 binds to T cells in a beta-galactoside-specific manner and acts as pro-apoptotic effector for activated T cells. 11730656_a_at LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), memberExtracellular 3 Space other down 0 -1.2429 ILMN_1786303 LILRA3 down 0 -0.3782 11752506_s_at LMNA lamin A/C Nucleus other up 0.0006 0.7529 ILMN_1696749 LMNA up 0.0145 0.3132 11729750_a_at LPAR1 lysophosphatidic acid receptor 1 Plasma Membrane G-protein coupled receptor down 0.0201 -0.4994 ILMN_1701441 LPAR1 updown 0.0437 0.0487 0.163 -0.2085 11743071_a_at LPAR6 lysophosphatidic acid receptor 6 Plasma Membrane G-protein coupled receptor down 0 -1.0977 ILMN_1786429 LPAR6 updown 0.0013 0 0.201 -0.7261 11725368_at LRG1 leucine-rich alpha-2-glycoprotein 1 Extracellular Space other down 0.0041 -0.5804 ILMN_1805228 LRG1 updown 0.0008 0.0002 0.3841 -0.4255 11751459_x_at LRG1 leucine-rich alpha-2-glycoprotein 1 Extracellular Space other down 0.0075 -0.5688 11734144_s_at LRRC37A3 (includes others)leucine rich repeat containing 37, member A3 unknown other up 0.0317 0.642 ILMN_1783673 LRRC37A3 (includes others)up 0.0293 0.1993 11724886_a_at LRRN3 leucine rich repeat neuronal 3 Extracellular Space other up 0.0418 0.6825 ILMN_1773650 LRRN3 updown 0.0004 0.0039 0.4995 -0.1381 11753808_s_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other down 0 -0.8583 ILMN_1719032 LSM3 down 0.0007 -0.3023 11753809_x_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other down 0 -0.7815 11716311_x_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other down 0 -0.7062 11757092_s_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other down 0 -0.8593 11723958_s_at LSM5 LSM5 homolog, U6 small nuclear RNA associated (S. cerevisiae) Cytoplasm other down 0.0428 -0.5703 ILMN_1737947 LSM5 down 0.0014 -0.3694 19840871 LY96 (MD-2) recognizes only exogenous pathogen-associated molecular patterns (PAMPs) when complexed with TLR2-CD14 or TLR4-CD14. 11723957_x_at LSM5 LSM5 homolog, U6 small nuclear RNA associated (S. cerevisiae) Cytoplasm other down 0.0444 -0.4362 15852007 LY86 and CD180 interact directly with the TLR4 signalling complex, inhibiting its ability to bind microbial ligand. 11724926_at LTN1 listerin E3 ubiquitin protein ligase 1 Nucleus enzyme down 0.0093 -0.776 ILMN_1760360 LTN1 down 0.0001 -0.5772 10359581 LY96 is physically associated with TLR4 on the cell surface and confers responsiveness to lipopolysaccharide (LPS). 11717464_at LXN latexin Cytoplasm other down 0.0182 -0.6364 ILMN_1723962 LXN down 0.008 -0.3393 22433852 Amino acid Phe126 of LY96 acts as a hydrophobic switch driving agonist-dependent contacts necessary for TLR4 dimerization and activation. 11715419_at LY6E lymphocyte antigen 6 complex, locus E Plasma Membrane other up 0.0007 0.8326 ILMN_1695404 LY6E updown 0 0.0201 0.6566 -0.1465 22474354 Morphine binds to LY96, triggering TLR4 oligomerization and induces neuroinflammation within the central nervous system. 11728507_at LY96 lymphocyte antigen 96 Plasma Membrane other down 0 -0.7867 ILMN_1724533 LY96 updown 0.0095 0 -0.1922 -0.9049 LY96 21712422 TLR4::LY96 functions as intracellular LPS sensor and triggers a unique set of LPS responses upon recognition of phagocytosed bacteria in macrophages. (Demonstrated in murine model) 11743772_a_at LZTFL1 leucine zipper transcription factor-like 1 unknown other down 0.0016 -0.8364 ILMN_1815705 LZTFL1 down 0 -0.4441 11757798_s_at MAFB v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) Nucleus other up 0.0119 0.3913 ILMN_1764709 MAFB up 0 0.466 MAFB 20581830 MAFB binds to IRF3, impairing the recruitment of co-activators to IRF3 and antagonizing antiviral responses. 11721630_at MAFB v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) Nucleus other up 0.0128 0.4674 11732456_a_at MARCH1 membrane-associated ring finger (C3HC4) 1, E3 ubiquitin protein ligase Cytoplasm enzyme down 0.0168 -0.8115 ILMN_1799106 MARCH1 down 0.021 -0.2585 11737203_a_at MARCH8 membrane-associated ring finger (C3HC4) 8, E3 ubiquitin protein ligase Cytoplasm enzyme up 0.0398 0.5462 ILMN_1677318 MARCH8 up 0.0192 0.3904 11723771_a_at MASTL microtubule associated serine/threonine kinase-like Cytoplasm kinase down 0.0001 -0.8598 ILMN_1682336 MASTL down 0.0014 -0.3577 11743661_a_at MBNL1 muscleblind-like splicing regulator 1 Nucleus other down 0.003 -0.732 ILMN_1807304 MBNL1 down 0 -0.5754 11717748_x_at MCTS1 malignant T cell amplified sequence 1 Cytoplasm other down 0.0071 -0.7754 ILMN_1751816 MCTS1 down 0.0279 -0.294 11717747_s_at MCTS1 malignant T cell amplified sequence 1 Cytoplasm other down 0.0074 -0.7969 11741446_s_at MED7 mediator complex subunit 7 Nucleus transcription regulator down 0.0004 -0.8438 ILMN_1739770 MED7 down 0.0242 -0.3022 11716176_s_at METAP2 methionyl aminopeptidase 2 Cytoplasm peptidase PPI-2458 down 0.012 -0.7078 ILMN_1670420 METAP2 down 0.0005 -0.3853 11722132_a_at MGAT3 mannosyl (beta-1,4-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase Cytoplasm enzyme up 0.0389 0.6871 ILMN_1853824 MGAT3 up 0.0457 0.2519 11729172_s_at MKI67IP MKI67 (FHA domain) interacting nucleolar phosphoprotein Nucleus other down 0.0173 -0.6996 ILMN_1786189 MKI67IP down 0.0003 -0.4136 11752512_a_at MLL myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila) Nucleus transcription regulator up 0.0238 0.4077 ILMN_1679003 MLL up 0.0035 0.3816 11751744_a_at MMD monocyte to macrophage differentiation-associated Plasma Membrane other up 0.0025 0.6364 ILMN_1733937 MMD up 0.0374 0.1579 21873432 MMP9 and NEU1 cross-talk in alliance with TLR4 on the cell surface is a novel membrane sialidase-controlling mechanism that depends on ligand binding to its Toll-like receptor (TLR) to induce NEU1 activity, to influence receptor desialylation and subseque 11728553_a_at MMP25 matrix metallopeptidase 25 Extracellular Space peptidase down 0.0303 -0.4938 ILMN_1717207 MMP25 updown 0.0384 0.0007 0.3336 -0.2494 22496659 MMP9 inhibits influenza virus pathogenesis by mediating neutrophil migration to the respiratory tract. (Demonstrated in mice) 11719657_a_at MMP9 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)Extracellular Space peptidase updown 0.0133 0 0.861 -0.9464 ILMN_1796316 MMP9 updown 0.007 0 0.1773 -0.5114 MMP9 22860023 MMP9 cleaves the pulmonary collectin SFTPD (SP-D) leading to loss of its innate immune functions. (Demonstrated in mouse) 11756876_a_at MNF1 mitochondrial nucleoid factor 1 Cytoplasm other down 0.0119 -0.7058 ILMN_1790461 MNF1 down 0.0073 -0.3617 11739833_a_at MOB4 MOB family member 4, phocein Cytoplasm other down 0 -1.0502 ILMN_1733356 MOB4 down 0.0003 -0.3917 11719073_a_at MOB4 MOB family member 4, phocein Cytoplasm other down 0.0001 -0.8506 11739834_s_at MOB4 MOB family member 4, phocein Cytoplasm other down 0.0308 -0.6211 11740944_at MPL myeloproliferative leukemia virus oncogene Plasma Membrane transmembrane receptor eltrombopag, romiplostimup 0.003 0.6435 ILMN_1776640 MPL up 0.0314 0.2147 11752958_a_at MPP1 membrane protein, palmitoylated 1, 55kDa Plasma Membrane kinase up 0.0297 0.6109 ILMN_1733675 MPP1 up 0.0001 0.4484 11715771_a_at MRPL13 mitochondrial ribosomal protein L13 Cytoplasm other down 0 -1.0284 ILMN_1671158 MRPL13 down 0 -0.4064 11715772_x_at MRPL13 mitochondrial ribosomal protein L13 Cytoplasm other down 0 -1.0046 11757551_a_at MRPL3 mitochondrial ribosomal protein L3 Cytoplasm other down 0.001 -0.7842 ILMN_1713143 MRPL3 down 0 -0.6039 11745391_x_at MRPL3 mitochondrial ribosomal protein L3 Cytoplasm other down 0.0044 -0.6855 11754766_a_at MRPL32 mitochondrial ribosomal protein L32 Cytoplasm translation regulator down 0.004 -0.8069 ILMN_1749432 MRPL32 down 0 -0.5391 11717459_a_at MRPL39 mitochondrial ribosomal protein L39 Cytoplasm other down 0.0396 -0.597 ILMN_1726391 MRPL39 down 0.0428 -0.2641 11717987_a_at MRPL40 mitochondrial ribosomal protein L40 Cytoplasm other down 0.0066 -0.6277 ILMN_1687403 MRPL40 down 0.0015 -0.413 11743806_x_at MRPL42 mitochondrial ribosomal protein L42 Cytoplasm other down 0 -1.2126 ILMN_1781420 MRPL42 down 0.0394 -0.2892 11748157_a_at MRPL42 mitochondrial ribosomal protein L42 Cytoplasm other down 0 -1.3204 11743805_s_at MRPL42 mitochondrial ribosomal protein L42 Cytoplasm other down 0.0056 -0.7961 11721262_at MRPL50 mitochondrial ribosomal protein L50 Cytoplasm other down 0 -0.9235 ILMN_1664833 MRPL50 down 0 -0.4729 11724783_a_at MRPS18C mitochondrial ribosomal protein S18C Cytoplasm other down 0 -0.9236 ILMN_1658416 MRPS18C down 0 -0.4534 11724785_x_at MRPS18C mitochondrial ribosomal protein S18C Cytoplasm other down 0.0017 -0.7677 11724784_at MRPS18C mitochondrial ribosomal protein S18C Cytoplasm other down 0.0034 -0.8389 11730249_at MRPS28 mitochondrial ribosomal protein S28 Cytoplasm other down 0.0125 -0.5767 ILMN_1718424 MRPS28 down 0.0203 -0.3225 11733134_a_at MRPS33 mitochondrial ribosomal protein S33 Cytoplasm other down 0.0003 -0.6723 ILMN_1772722 MRPS33 down 0.0031 -0.3378 11756780_a_at MS4A7 membrane-spanning 4-domains, subfamily A, member 7 unknown other up 0.0387 0.5099 ILMN_1743932 MS4A7 updown 0.0101 0.0261 0.2442 -0.2843 11740092_x_at MSMO1 methylsterol monooxygenase 1 Cytoplasm enzyme down 0.0281 -0.5029 ILMN_1720889 MSMO1 down 0.0483 -0.3125 21460221 MSR1 deficiency leads to greater sensitivity to LPS-induced endotoxic shock. MSR1 down-regulates inflammatory gene expression in dendritic cells by suppressing TLR4-mediated activation of NFKB. 11741012_a_at MSMO1 methylsterol monooxygenase 1 Cytoplasm enzyme down 0.0406 -0.4938 19914718 MSR1 is required for sensing human cytomegalovirus (HCMV) by endosomal TLR3 and TLR9 in monocytic THP-1 cells. 11737428_a_at MSR1 macrophage scavenger receptor 1 Plasma Membrane transmembrane receptor up 0 0.7567 ILMN_1743301 MSR1 up 0.0174 0.184 MSR1 20162551 MRS1 (SR-A) is upregulated in TLR4-mediated LPS responses and these receptors contribute to the efficient capturing and clearance of invading microbial pathogens. 11756089_s_at MSR1 macrophage scavenger receptor 1 Plasma Membrane transmembrane receptor up 0.0002 0.8107 21756882 MSR1, one of the principal receptors expressed on macrophages, suppresses macrophage activation by inhibiting the binding of lipopolysaccharide (LPS) to TLR4 in a competitive manner; thus playing a pivotal role in the regulation of the LPS-induced inflamm 11737429_x_at MSR1 macrophage scavenger receptor 1 Plasma Membrane transmembrane receptor up 0.003 0.548 22751446 Deletion of MSR1 results in protection from septic shock and modulation of TLR4 signalling in peritoneal macrophages. (Demonstrated in mice) 11745892_a_at MTHFD2 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolateCytoplasm cyclohydrolaseenzyme down 0.0013 -0.605 ILMN_1674706 MTHFD2 down 0 -0.5473 11744002_s_at MTHFD2 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolateCytoplasm cyclohydrolaseenzyme down 0.0306 -0.6148 18062906 MX1 is an interferon-induced member of the dynamin superfamily of large GTPases, which inhibit a wide range of viruses by blocking an early stage of the replication cycle. 11716167_a_at MX1 myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse)Nucleus enzyme updown 0.0063 0.0098 0.3953 -0.4542 ILMN_1662358 MX1 updown 0.0009 0 0.4928 -0.5374 MX1 22531919 MX1 expression is upregulated by alpha-defensins in gigival epithelial cell. 11720703_at MYL4 myosin, light chain 4, alkali; atrial, embryonic Cytoplasm other up 0.0114 0.5813 ILMN_1684255 MYL4 up 0.0032 0.4904 20538602 MX1 GTPase is a key mediator of cell-autonomous innate immunity against a broad range of viruses such as influenza and bunyaviruses. 11729192_a_at MYNN myoneurin Nucleus transcription regulator down 0 -1.0925 ILMN_1672287 MYNN down 0 -0.5979 11729193_s_at MYNN myoneurin Nucleus transcription regulator down 0.0002 -0.9008 11749019_a_at MYNN myoneurin Nucleus transcription regulator down 0.003 -0.8009 11729194_s_at MYNN myoneurin Nucleus transcription regulator down 0.0183 -0.5698 11718168_a_at MYOF myoferlin Nucleus other up 0.0002 0.5962 ILMN_1810289 MYOF up 0.0016 0.284 11754928_x_at MYOF myoferlin Nucleus other up 0.0011 0.5357 Page 89 of 111 Diabetes

11725136_a_at MYOM2 myomesin (M-protein) 2, 165kDa Cytoplasm other up 0 0.7051 ILMN_1716733 MYOM2 updown 0 0.0244 1.1231 0.5793 11739475_s_at NAB1 NGFI-A binding protein 1 (EGR1 binding protein 1) Nucleus transcription regulator down 0.0483 -0.5649 ILMN_1774617 NAB1 down 0.0007 -0.2755 18280719 NAIP is important for CASP1 activation and IL-1 processing. 11736898_s_at NAIP NLR family, apoptosis inhibitory protein unknown other down 0.0074 -0.7494 ILMN_1788237 NAIP down 0.0338 -0.1253 NAIP 21918512 NAIP specifically recognizes the Chromobacterium violaceum type III secretion system protein, Cprl, and activates the NLRC4 inflammasome in macrophages. 11760312_at NAMPT nicotinamide phosphoribosyltransferase Extracellular Space cytokine updown 0.0047 0.031 0.4065 -0.6038 ILMN_1753111 NAMPT updown 0.0088 0.0003 0.3061 -0.4111 NAMPT 22377803 NAMPT secretion is enhanced by extracellular ATP in LPS-primed monocytes. ILMN_1653871 NAMPT down 0 -0.4544 11722826_a_at NCAPG non-SMC condensin I complex, subunit G Nucleus other down 0.0025 -0.6012 ILMN_1751444 NCAPG down 0.0064 -0.3186 11753867_a_at NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, 7.5kDa Cytoplasm enzyme down 0.0261 -0.5281 ILMN_1784286 NDUFA1 updown 0.0293 0 0.1928 -0.5223 11723291_a_at NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, 7.5kDa Cytoplasm enzyme down 0.0364 -0.53 11756125_x_at NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, 7.5kDa Cytoplasm enzyme down 0.0377 -0.4614 11715369_s_at NDUFA4 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDa Cytoplasm enzyme down 0 -1.0384 ILMN_1751258 NDUFA4 down 0 -0.7224 11758717_x_at NDUFA4 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDa Cytoplasm enzyme down 0 -0.9726 11716340_a_at NDUFS4 NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase)Cytoplasm enzyme down 0.0003 -0.8258 ILMN_1812312 NDUFS4 down 0 -0.4155 11755471_a_at NECAB2 N-terminal EF-hand calcium binding protein 2 Cytoplasm other down 0.0018 -0.456 ILMN_1663437 NECAB2 down 0.0013 -0.2951 11722865_at NETO2 neuropilin (NRP) and tolloid (TLL)-like 2 unknown other down 0.0436 -0.5176 ILMN_1760849 NETO2 down 0.0003 -0.3771 11726798_a_at NEXN nexilin (F actin binding protein) Plasma Membrane other up 0.0161 0.3873 ILMN_1783276 NEXN up 0.0123 0.174 11749172_x_at NEXN nexilin (F actin binding protein) Plasma Membrane other up 0.0177 0.2904 11754911_x_at NEXN nexilin (F actin binding protein) Plasma Membrane other up 0.0238 0.5284 11749795_a_at NFIX nuclear factor I/X (CCAAT-binding transcription factor) Nucleus transcription regulator up 0 1.1275 ILMN_1694325 NFIX up 0.0036 0.3707 11750285_a_at NFIX nuclear factor I/X (CCAAT-binding transcription factor) Nucleus transcription regulator up 0.0012 0.77 11750902_x_at NFIX nuclear factor I/X (CCAAT-binding transcription factor) Nucleus transcription regulator up 0.003 0.7619 11759378_at NHSL2 NHS-like 2 unknown other up 0.0334 0.7687 ILMN_1748694 NHSL2 up 0.0013 0.4104 11717155_a_at NME1 NME/NM23 nucleoside diphosphate kinase 1 Cytoplasm kinase down 0.0412 -0.5546 ILMN_1741133 NME1 down 0.0145 -0.2315 11715824_at NOP10 NOP10 ribonucleoprotein homolog (yeast) Nucleus other down 0.0449 -0.4341 ILMN_1815479 NOP10 down 0 -0.3953 11761655_at NPCDR1 nasopharyngeal carcinoma, down-regulated 1 unknown other up 0.0037 0.5476 ILMN_1780774 NPCDR1 up 0.0085 0.1819 11753912_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0 0.9403 ILMN_1733581 NPRL3 up 0 0.7397 11748257_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0 0.9124 11763176_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0 0.8698 11724497_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0 0.8661 11724496_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0.0172 0.6272 11724337_s_at NRCAM neuronal cell adhesion molecule Plasma Membrane other up 0.0032 0.3821 ILMN_1722809 NRCAM up 0.0249 0.271 11746395_x_at NRCAM neuronal cell adhesion molecule Plasma Membrane other up 0.0221 0.6776 11718787_at NRGN neurogranin (protein kinase C substrate, RC3) Cytoplasm other up 0.0002 0.8663 ILMN_1705686 NRGN updown 0 0.0053 0.8618 -0.2634 11721042_at NSMCE2 non-SMC element 2, MMS21 homolog (S. cerevisiae) Nucleus enzyme down 0.0011 -0.8193 ILMN_1693210 NSMCE2 down 0.0006 -0.3983 11740934_a_at NUSAP1 nucleolar and spindle associated protein 1 Nucleus other down 0.011 -0.4513 ILMN_1726720 NUSAP1 down 0 -0.2937 11742735_a_at NUSAP1 nucleolar and spindle associated protein 1 Nucleus other down 0.0213 -0.4369 11724255_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme updown 0.0017 0.0015 0.6139 -0.207 ILMN_1658247 OAS1 updown 0 0 0.807 -0.5813 OAS1 23319625 OAS1 is a cytoplasmic dsRNA sensor. 11740891_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme updown 0.001 0.0053 0.6887 -0.3492 ILMN_1675640 OAS1 updown 0 0.0031 0.5202 -0.374 21190483 OAS1 is a pathogen recognition receptor for the viral pathogen-associated molecular pattern, double-stranded RNA. Upon recognition of dsRNA, the OAS1 activates RNASEL to cleave ssRNA. The OAS/RNASEL pathway triggers the RIG-I pathway and induce IFNB produ 11719588_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme updown 0.0025 0.0127 0.7215 -0.4305 11724256_s_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme up 0.0473 0.3685 11723698_a_at OAS3 2-5-oligoadenylate synthetase 3, 100kDa Cytoplasm enzyme updown 0 0.0053 0.8259 -0.549 ILMN_1745397 OAS3 updown 0 0.002 0.4061 -0.1366 OAS3 21190483 OAS3 is a pathogen recognition receptor for the viral pathogen-associated molecular pattern, double-stranded RNA. Upon recognition of dsRNA, the OAS3 activates RNASEL to cleave ssRNA. The OAS/RNASEL pathway triggers the RIG-I pathway and induce IFNB produ 11723699_s_at OAS3 2-5-oligoadenylate synthetase 3, 100kDa Cytoplasm enzyme updown 0.0002 0.0284 0.7852 -0.445 11726364_x_at OASL 2-5-oligoadenylate synthetase-like Cytoplasm enzyme up 0 0.7509 ILMN_1674811 OASL up 0 0.4344 11736090_a_at OLIG2 oligodendrocyte lineage transcription factor 2 Nucleus transcription regulator updown 0 0.0019 0.4819 -0.3641 ILMN_1727567 OLIG2 updown 0 0 0.3418 -0.2408 11744904_a_at ORM1 orosomucoid 1 Extracellular Space other down 0 -1.1353 ILMN_1696584 ORM1 down 0.0004 -0.3789 11744905_x_at ORM1 orosomucoid 1 Extracellular Space other down 0 -0.9423 11754065_x_at ORM1 orosomucoid 1 Extracellular Space other down 0 -0.9092 11758794_x_at ORM1 orosomucoid 1 Extracellular Space other down 0 -0.9715 11736300_a_at ORMDL1 ORM1-like 1 (S. cerevisiae) Cytoplasm other down 0.0024 -0.9187 ILMN_1698406 ORMDL1 down 0.0287 -0.3775 11736205_a_at OSBP2 oxysterol binding protein 2 Cytoplasm other up 0 0.9202 ILMN_1781966 OSBP2 up 0.0015 0.2291 11736206_a_at OSBP2 oxysterol binding protein 2 Cytoplasm other up 0.0038 0.7243 11750705_a_at OSBP2 oxysterol binding protein 2 Cytoplasm other up 0.0042 0.8839 11723734_s_at OTUD6B OTU domain containing 6B unknown other down 0.0054 -0.7293 ILMN_1772703 OTUD6B down 0.0329 -0.3135 11723341_x_at OXR1 oxidation resistance 1 Cytoplasm other down 0.0071 -0.7034 ILMN_1737462 OXR1 down 0 -0.7455 11730956_a_at P2RX1 purinergic receptor P2X, ligand-gated ion channel, 1 Plasma Membrane ion channel down 0.0133 -0.5951 ILMN_1758529 P2RX1 down 0.026 -0.2067 11752300_a_at PADI2 peptidyl arginine deiminase, type II Cytoplasm enzyme up 0.0154 0.4848 ILMN_1771223 PADI2 up 0.0141 0.2726 11749412_a_at PARP14 poly (ADP-ribose) polymerase family, member 14 Cytoplasm other up 0.0063 0.5551 ILMN_1691731 PARP14 up 0.0001 0.3959 11721998_a_at PARP14 poly (ADP-ribose) polymerase family, member 14 Cytoplasm other up 0.0366 0.5511 11754379_at PARP9 poly (ADP-ribose) polymerase family, member 9 Nucleus other up 0 0.8461 ILMN_1731224 PARP9 updown 0.0004 0.0126 0.308 -0.1838 11756306_a_at PARP9 poly (ADP-ribose) polymerase family, member 9 Nucleus other up 0.0161 0.5242 11726186_x_at PARPBP PARP1 binding protein Nucleus other down 0.012 -0.5415 ILMN_1727055 PARPBP down 0.0458 -0.2154 11747110_a_at PASK PAS domain containing serine/threonine kinase Cytoplasm kinase up 0.0172 0.5657 ILMN_1667022 PASK up 0 0.7945 11756562_a_at PDCD10 programmed cell death 10 Cytoplasm other down 0 -0.946 ILMN_1766024 PDCD10 down 0.0003 -0.3189 11718804_x_at PDCD10 programmed cell death 10 Cytoplasm other down 0.0001 -1.0278 11718803_a_at PDCD10 programmed cell death 10 Cytoplasm other down 0.0003 -0.8178 11716974_a_at PDK4 pyruvate dehydrogenase kinase, isozyme 4 Cytoplasm kinase up 0.0019 0.8167 ILMN_1684982 PDK4 up 0.0009 0.3277 11723504_x_at PDPR pyruvate dehydrogenase phosphatase regulatory subunit Cytoplasm enzyme up 0.0048 0.7129 ILMN_1667034 PDPR up 0.0034 0.4439 ILMN_1778013 PDPR up 0.0243 0.231 11756227_s_at PEX2 peroxisomal biogenesis factor 2 Cytoplasm other down 0.0004 -0.9122 ILMN_1743299 PEX2 down 0 -0.6648 11720549_a_at PEX6 peroxisomal biogenesis factor 6 Cytoplasm enzyme up 0.0201 0.4875 ILMN_1683279 PEX6 up 0.0019 0.3416 11750089_x_at PFDN5 prefoldin subunit 5 Nucleus transcription regulator down 0.003 -0.5987 ILMN_1755536 PFDN5 down 0 -0.4679 11716608_a_at PFDN5 prefoldin subunit 5 Nucleus transcription regulator down 0.0053 -0.6078 20418257 PGLYRP1 is a secreted innate immunity protein that is expressed in polymorphonuclear leukocytes and is conserved from insects to mammals, it recognizes bacterial peptidoglycan, and functions in antibacterial immunity and inflammation. 11757641_x_at PFDN5 prefoldin subunit 5 Nucleus transcription regulator down 0.0115 -0.5288 21602801 PGLYRP1 binds to Gram-positive bacterial wall and activates a protein-sensing two-component system to induce bacterial death. PLGYRP1-mediated activation results in membrane depolarization and cessation of peptidoglycan, protein, and RNA/DNA synthesis, as 11732642_at PGLYRP1 peptidoglycan recognition protein 1 Plasma Membrane transmembrane receptor down 0.0173 -0.37 ILMN_1704870 PGLYRP1 updown 0.0016 0 0.1594 -0.4631 PGLYRP1 21134971 PGLYRP1 is a peptidoglycan recognition protein and play a role in innate immunity against L. monocytogenes infection by inducing TNFA. (Demonstrated in murine model) 11756898_a_at PGM5 phosphoglucomutase 5 Cytoplasm enzyme up 0.0004 0.4099 ILMN_1781388 PGM5 up 0.0415 0.1807 21439073 PGLYRP1 is a member of the Peptidoglycan Recognition Proteins (PGRP) family and recognizes peptidoglycan, a structural component of bacterial cell walls, as a part of innate immune response against infections. 11733294_at PHF20L1 PHD finger protein 20-like 1 unknown other down 0.0324 -0.6444 ILMN_1732985 PHF20L1 down 0.0005 -0.4528 11721650_at PI3 peptidase inhibitor 3, skin-derived Extracellular Space other down 0 -0.9 ILMN_1693192 PI3 updown 0.0015 0 0.1992 -0.9368 11754722_s_at PI4K2B phosphatidylinositol 4-kinase type 2 beta Cytoplasm kinase down 0.0193 -0.6005 ILMN_1815134 PI4K2B down 0.0005 -0.3816 11725271_a_at PIGA phosphatidylinositol glycan anchor biosynthesis, class A Cytoplasm enzyme down 0.0072 -0.7932 ILMN_1705985 PIGA down 0.0001 -0.5207 11737863_s_at PIGF phosphatidylinositol glycan anchor biosynthesis, class F Cytoplasm enzyme down 0.0275 -0.6012 ILMN_1808938 PIGF down 0.01 -0.3077 11721855_a_at PIGK phosphatidylinositol glycan anchor biosynthesis, class K Cytoplasm peptidase down 0.0189 -0.6282 ILMN_1772743 PIGK down 0.0026 -0.3929 11748524_x_at PIGK phosphatidylinositol glycan anchor biosynthesis, class K Cytoplasm peptidase down 0.0421 -0.5502 11721345_at PLEK2 pleckstrin 2 unknown other up 0.0079 0.6007 ILMN_1811470 PLEK2 up 0.0066 0.3155 11722966_a_at PLEKHA1 pleckstrin homology domain containing, family A (phosphoinositide binding specific)Cytoplasm member 1 other down 0.0497 -0.4239 ILMN_1662839 PLEKHA1 down 0.0003 -0.3901 21779477 Pml(-/-) mice are resistant to LPS-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-kB pathway. Pml(-/-) mice also exhibit impaired functi 11728557_s_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.0157 0.5793 ILMN_1728019 PML up 0.0242 0.2151 PML 21131187 PML, a member of the TRIM protein family, is upregulated by Type I and Type II interferons and have been found to restrict viral replication by modulating the RIG-I pathway. 11726876_a_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.0173 0.5599 11715585_a_at PMP22 peripheral myelin protein 22 Plasma Membrane other up 0 0.8729 ILMN_1785646 PMP22 up 0 0.398 11718762_s_at POMP proteasome maturation protein Nucleus other down 0.0036 -0.7329 ILMN_1693287 POMP down 0.0007 -0.4182 11743087_at PPBP pro-platelet basic protein (chemokine (C-X-C motif) ligand 7) Extracellular Space cytokine down 0.0021 -0.5099 ILMN_1767281 PPBP down 0.0024 -0.3764 11730267_a_at PPIG peptidylprolyl isomerase G (cyclophilin G) Nucleus enzyme down 0.0002 -0.9062 ILMN_1807611 PPIG down 0.0005 -0.359 11754214_a_at PPIG peptidylprolyl isomerase G (cyclophilin G) Nucleus enzyme down 0.0057 -0.5683 11744828_a_at PPIL3 peptidylprolyl isomerase (cyclophilin)-like 3 Cytoplasm enzyme down 0.0114 -0.7192 ILMN_1770020 PPIL3 down 0.0003 -0.4186 11747295_a_at PRF1 perforin 1 (pore forming protein) Cytoplasm other up 0.0047 0.6894 ILMN_1740633 PRF1 up 0.0009 0.2181 11759796_at PRIC285 peroxisomal proliferator-activated receptor A interacting complex 285 Nucleus transcription regulator up 0.0156 0.5498 ILMN_1787509 PRIC285 updown 0 0.0106 0.5109 -0.3301 11726803_x_at PRIC285 peroxisomal proliferator-activated receptor A interacting complex 285 Nucleus transcription regulator up 0.025 0.4713 11732808_a_at PROK2 prokineticin 2 Extracellular Space other down 0 -0.7965 ILMN_1775257 PROK2 updown 0.0055 0 0.2874 -0.8313 11732809_a_at PROK2 prokineticin 2 Extracellular Space other down 0.0018 -0.5917 11716568_a_at PRRC2C proline-rich coiled-coil 2C Cytoplasm other up 0.0047 0.631 ILMN_1743137 PRRC2C up 0.0404 0.2556 11731941_at PRSS33 protease, serine, 33 Extracellular Space peptidase up 0 0.7016 ILMN_1736831 PRSS33 up 0 0.2728 11721905_a_at PSMA4 proteasome (prosome, macropain) subunit, alpha type, 4 Cytoplasm peptidase down 0.0001 -0.8315 ILMN_1682098 PSMA4 down 0.0005 -0.358 11742892_s_at PSMA4 proteasome (prosome, macropain) subunit, alpha type, 4 Cytoplasm peptidase down 0.0129 -0.6328 11721906_s_at PSMA4 proteasome (prosome, macropain) subunit, alpha type, 4 Cytoplasm peptidase down 0.014 -0.6651 11757295_x_at PSMA6 proteasome (prosome, macropain) subunit, alpha type, 6 Cytoplasm peptidase down 0.0015 -0.8891 ILMN_1704094 PSMA6 down 0.0011 -0.3531 11720983_s_at PSMC6 proteasome (prosome, macropain) 26S subunit, ATPase, 6 Nucleus peptidase down 0.0001 -0.8447 ILMN_1655316 PSMC6 down 0 -0.473 11758115_s_at PTBP2 polypyrimidine tract binding protein 2 Nucleus other down 0.0026 -0.7903 ILMN_1707240 PTBP2 down 0.0002 -0.4115 11722804_x_at PTBP2 polypyrimidine tract binding protein 2 Nucleus other down 0.0192 -0.6465 11728067_at PTGDR2 prostaglandin D2 receptor 2 Plasma Membrane G-protein coupled receptor up 0.0029 0.3492 ILMN_1703326 PTGDR2 updown 0.0017 0.0151 0.0953 -0.3767 11725685_a_at PTPRO protein tyrosine phosphatase, receptor type, O Plasma Membrane phosphatase down 0.0471 -0.5295 ILMN_1720113 PTPRO down 0.0006 -0.4033 11728455_at RAB33B RAB33B, member RAS oncogene family Cytoplasm enzyme down 0.0093 -0.5365 ILMN_1727738 RAB33B down 0.0193 -0.2886 11725237_a_at RBPMS2 RNA binding protein with multiple splicing 2 unknown other up 0 0.8559 ILMN_1808238 RBPMS2 up 0 0.4659 11716335_x_at RBX1 ring-box 1, E3 ubiquitin protein ligase Cytoplasm enzyme down 0.0159 -0.6927 ILMN_1666670 RBX1 down 0 -0.5744 11729123_a_at RCN2 reticulocalbin 2, EF-hand calcium binding domain Cytoplasm other down 0.001 -0.886 ILMN_1662129 RCN2 down 0 -0.5236 11729124_x_at RCN2 reticulocalbin 2, EF-hand calcium binding domain Cytoplasm other down 0.004 -0.831 11723454_at RIOK2 RIO kinase 2 (yeast) unknown kinase down 0.0354 -0.6763 ILMN_1655329 RIOK2 down 0.0356 -0.2307 11755743_a_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme down 0 -0.8708 ILMN_1730628 RNASE2 updown 0.0246 0 0.0506 -0.635 11729772_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme down 0 -0.8255 11741447_s_at RNASE4 ribonuclease, RNase A family, 4 Extracellular Space enzyme down 0.0001 -0.6621 ILMN_1776602 RNASE4 down 0.0195 -0.2438 11718988_s_at RNASE4 ribonuclease, RNase A family, 4 Extracellular Space enzyme down 0.0049 -0.4602 11733014_a_at RNF213 ring finger protein 213 Plasma Membrane enzyme up 0.0221 0.529 ILMN_1749722 RNF213 up 0.004 0.2687 11720349_at ROPN1L rhophilin associated tail protein 1-like Cytoplasm kinase down 0.0069 -0.1858 ILMN_1696466 ROPN1L down 0.0038 -0.3672 11744328_x_at RPL17 ribosomal protein L17 Cytoplasm other down 0.0017 -0.7925 ILMN_1658283 RPL17 updown 0.0012 0 0.155 -0.8408 200038_PM_s_at RPL17 ribosomal protein L17 Cytoplasm other down 0.0029 -0.8016 11754996_x_at RPL17 ribosomal protein L17 Cytoplasm other down 0.0049 -0.7374 11757329_s_at RPL26 ribosomal protein L26 Cytoplasm other down 0 -1.131 ILMN_1731546 RPL26 updown 0.0005 0 0.1646 -0.9549 11757421_x_at RPL31 ribosomal protein L31 Nucleus other down 0 -0.9388 ILMN_1754195 RPL31 updown 0.0169 0 -0.168 -0.812 11757027_x_at RPL31 ribosomal protein L31 Nucleus other down 0 -0.8851 11729387_x_at RPL31 ribosomal protein L31 Nucleus other down 0.0021 -0.746 11729386_s_at RPL31 ribosomal protein L31 Nucleus other down 0.0057 -0.6921 11760320_at RPL31 ribosomal protein L31 Nucleus other down 0.0109 -0.7104 11746229_a_at RPL31 ribosomal protein L31 Nucleus other down 0.0195 -0.4164 11763301_x_at RPL39 ribosomal protein L39 Cytoplasm other down 0 -0.9206 ILMN_1737015 RPL39 updown 0.0105 0 -0.2028 -1.0745 11757673_x_at RPL39 ribosomal protein L39 Cytoplasm other down 0.0035 -0.5335 11715958_s_at RPL7 ribosomal protein L7 Nucleus transcription regulator down 0 -1.0669 ILMN_1815292 RPL7 down 0.0023 -0.2639 11758357_x_at RPL9 ribosomal protein L9 Cytoplasm other down 0 -1.0197 ILMN_1750507 RPL9 down 0 -0.6979 11715237_s_at RPL9 ribosomal protein L9 Cytoplasm other down 0.0017 -0.704 11715238_x_at RPL9 ribosomal protein L9 Cytoplasm other down 0.0049 -0.6097 200032_PM_s_at RPL9 ribosomal protein L9 Cytoplasm other down 0.0117 -0.7353 11725714_a_at RPS14 ribosomal protein S14 Cytoplasm translation regulator down 0.0412 -0.528 ILMN_1666635 RPS14 down 0.0003 -0.4082 11723251_at RPS15A ribosomal protein S15a Cytoplasm other down 0 -1.1426 ILMN_1787949 RPS15A updown 0 0 0.3665 -0.9191 11719784_x_at RPS23 ribosomal protein S23 Cytoplasm translation regulator down 0.0201 -0.4694 ILMN_1772459 RPS23 down 0 -0.6153 11744350_a_at RPS27L ribosomal protein S27-like Nucleus other down 0 -0.9981 ILMN_1712678 RPS27L down 0 -0.6278 200099_PM_s_at RPS3A ribosomal protein S3A Cytoplasm other down 0.0004 -0.7421 ILMN_1673638 RPS3A down 0 -1.0447 11716320_x_at RPS3A ribosomal protein S3A Cytoplasm other down 0.0012 -0.6225 11757492_s_at RRAS2 related RAS viral (r-ras) oncogene homolog 2 Plasma Membrane enzyme down 0.0354 -0.7028 ILMN_1667519 RRAS2 down 0.0111 -0.3252 11758816_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.0017 -0.503 ILMN_1688178 RRP7A updown 0.0378 0 0.069 -0.3978 11758818_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.0135 -0.3851 11758817_x_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.0223 -0.2351 11739216_x_at RSAD2 radical S-adenosyl methionine domain containing 2 Cytoplasm enzyme updown 0 0 0.9923 -0.9999 ILMN_1657871 RSAD2 updown 0 0.0001 0.1799 -0.4345 RSAD2 20308629 RSAD2 (viperin) is an antiviral protein whose expression is highly upregulated during viral infections via IFN-dependent and/or IFN-independent pathways and an IRF1 mediated type I IFN independent mechanism of enhanced RSAD2 expression provides a redundan 11739217_a_at RSAD2 radical S-adenosyl methionine domain containing 2 Cytoplasm enzyme updown 0 0 1.3026 -0.9159 11746770_x_at RWDD4 RWD domain containing 4 unknown other down 0.0169 -0.7195 ILMN_1708660 RWDD4 down 0.039 -0.3292 11717539_at RYBP RING1 and YY1 binding protein Nucleus transcription regulator up 0.0073 0.7337 ILMN_1721842 RYBP up 0 0.4724 20555353 S100A8 (calgranulin A) and S100A9 (calgranulin B) form an antimicrobial heterodimeric complex known as calprotectin. Bacterial flagellin induces the upregulation of S100A8/S100A9 heterodimer via a TLR5-dependent mechanism in epidermal keratinocytes. 11725138_at S100A12 S100 calcium binding protein A12 Cytoplasm other down 0 -1.0537 ILMN_1748915 S100A12 down 0 -0.9194 12626582 S100A8 is an intracellular calcium-binding protein that promotes neutrophil/monocyte recruitment at inflamed tissues by enhancing attachment to endothelial cells. 11753823_a_at S100A8 S100 calcium binding protein A8 Cytoplasm other down 0.0012 -0.9048 ILMN_1729801 S100A8 down 0 -1.5244 S100A8 18714033 S100A8 is a myeloid-related protein that rapidly modulates macrophage nitric oxide production during innate immune response. 11718347_a_at S100P S100 calcium binding protein P Cytoplasm other down 0 -0.8729 ILMN_1801216 S100P down 0 -0.9581 21239714 S100A8 forms a complex with S100A9 and the complex is the site of interplay between extracellular Ca(2+) entry and intra-phagosomal reactive oxygen species production. S100A8 :: S100A9 acts as Ca(2+) sensor in phagosomal ROS production. 11755347_x_at SAR1B SAR1 homolog B (S. cerevisiae) Cytoplasm enzyme down 0 -0.9904 ILMN_1736888 SAR1B down 0.0008 -0.3567 23431180 S100A8::S100A9 heterodimer sequesters Mn(2+) and Zn(2+) to starve bacteria of these essential nutrients. 11725341_a_at SAR1B SAR1 homolog B (S. cerevisiae) Cytoplasm enzyme down 0 -0.9494 22423963 S100A8 is strongly upregulated in neutrophils upon bacterial infection, and sequesters zinc as a mechanism of nutritional immunity. Salmonella typhimurium overcomes this defence mechanism by expressing a high affinity zinc transporter. (Demonstrated in mi 11741124_a_at SAR1B SAR1 homolog B (S. cerevisiae) Cytoplasm enzyme down 0.0055 -0.6108 11744341_s_at SARNP SAP domain containing ribonucleoprotein Nucleus other down 0.0008 -0.7727 ILMN_1680967 SARNP down 0 -0.435 11734863_a_at SARNP SAP domain containing ribonucleoprotein Nucleus other down 0.008 -0.5767 11733054_a_at SCAMP1 secretory carrier membrane protein 1 Cytoplasm transporter down 0.049 -0.6612 ILMN_1728907 SCAMP1 down 0.0003 -0.456 11751213_s_at SCOC short coiled-coil protein Cytoplasm other down 0 -1.0597 ILMN_1768050 SCOC down 0.0003 -0.3849 11757358_s_at SCOC short coiled-coil protein Cytoplasm other down 0 -1.0656 11745739_a_at SCOC short coiled-coil protein Cytoplasm other down 0 -1.1432 11744264_a_at SEC11C SEC11 homolog C (S. cerevisiae) Cytoplasm peptidase down 0.0024 -0.5112 ILMN_1701681 SEC11C down 0.0001 -0.4394 11717753_a_at SEC14L1 SEC14-like 1 (S. cerevisiae) Cytoplasm transporter up 0.0211 0.7943 ILMN_1732575 SEC14L1 up 0.0008 0.4315 11716401_a_at SELENBP1 selenium binding protein 1 Cytoplasm other up 0 1.0565 ILMN_1680652 SELENBP1 up 0 0.6303 11758712_s_at SELT selenoprotein T Cytoplasm other down 0.0047 -0.5756 ILMN_1746368 SELT down 0.0039 -0.3903 11716027_at SELT selenoprotein T Cytoplasm other down 0.0093 -0.607 11716028_x_at SELT selenoprotein T Cytoplasm other down 0.0313 -0.5577 11726628_a_at SEMA4A sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and shortPlasma cytoplasmic Membrane domain, other (semaphorin) 4A down 0.0085 -0.733 ILMN_1702787 SEMA4A updown 0.007 0.0047 0.1484 -0.2537 11750712_a_at SEMA4A sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and shortPlasma cytoplasmic Membrane domain, other (semaphorin) 4A down 0.0227 -0.5419 11750423_a_at SEPSECS Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase Cytoplasm enzyme down 0.0011 -0.7705 ILMN_1750092 SEPSECS down 0.0392 -0.2242 11745226_a_at SEPT4 septin 4 Cytoplasm enzyme up 0 0.8237 ILMN_1778079 SEPT4 up 0.0167 0.3246 11720255_a_at SEPT5 septin 4 Cytoplasm enzyme up 0.0058 0.4839 11720256_x_at SEPT6 septin 4 Cytoplasm enzyme up 0.0068 0.5684 11745227_x_at SEPT7 septin 4 Cytoplasm enzyme up 0.0267 0.3138 11751845_x_at SERPING1 serpin peptidase inhibitor, clade G (C1 inhibitor), member 1 Extracellular Space other up 0 1.7627 ILMN_1670305 SERPING1 up 0 0.6454 SERPING1 17709141 A likely regulator of MASP2 Diabetes Page 90 of 111

11715368_a_at SERPING1 serpin peptidase inhibitor, clade G (C1 inhibitor), member 1 Extracellular Space other up 0 1.8015 11717671_a_at SF3B14 splicing factor 3B, 14 kDa subunit Nucleus other down 0.0036 -0.5777 ILMN_1703720 SF3B14 down 0 -0.538 18501771 The SLAM and SAP gene families control innate and adaptive immune responses 11728293_a_at SH2D1A SH2 domain containing 1A Cytoplasm other down 0 -0.8878 ILMN_1705892 SH2D1A down 0.0012 -0.3788 SH2D1A 19079134 SLAM receptors and SAP influence lymphocyte interactions, development and function 11728290_a_at SH2D1A SH2 domain containing 1A Cytoplasm other down 0.0011 -0.8534 11728292_at SH2D1A SH2 domain containing 1A Cytoplasm other down 0.0129 -0.6189 11728291_at SH2D1A SH2 domain containing 1A Cytoplasm other down 0.0429 -0.5129 11718447_s_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0 0.7143 ILMN_1762764 SH3BGRL2 up 0.0022 0.4019 11718446_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0.0003 0.5972 11718448_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0.0009 0.6354 11718445_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0.0486 0.494 11756240_a_at SHISA4 shisa homolog 4 (Xenopus laevis) unknown other up 0.0066 0.4484 ILMN_1677942 SHISA4 up 0.0193 0.3124 19596804 SIGLEC5 is bound by group B Streptococcus (GBS) beta protein and this functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. 11729739_at SIGLEC5 sialic acid binding Ig-like lectin 5 Plasma Membrane other down 0.0008 -0.679 ILMN_1740298 SIGLEC5 updown 0.0001 0 0.5888 -0.6275 SIGLEC5 21208791 SIGLEC5 is a member of the SIGLEC protein family that recognize sialoside-based patterns and plays a role in the attenuation of innate immunity to avoid autoimmune destruction. 11757924_s_at SIPA1L2 signal-induced proliferation-associated 1 like 2 unknown other down 0.0037 -0.6931 ILMN_1732923 SIPA1L2 down 0.0002 -0.3793 11744184_a_at SIPA1L2 signal-induced proliferation-associated 1 like 2 unknown other down 0.0059 -0.5106 11744185_a_at SIPA1L2 signal-induced proliferation-associated 1 like 2 unknown other down 0.0433 -0.4842 11727842_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter down 0.0082 -0.3185 ILMN_1741165 SLC11A1 down 0 -0.6306 11747774_a_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter down 0.0093 -0.5059 11724454_at SLC22A4 solute carrier family 22 (organic cation/ergothioneine transporter), member 4 Plasma Membrane transporter down 0.0194 -0.5178 ILMN_1685057 SLC22A4 down 0.0169 -0.2378 11717162_a_at SLC29A1 solute carrier family 29 (nucleoside transporters), member 1 Plasma Membrane transporter up 0.0064 0.5983 ILMN_1723971 SLC29A1 up 0.0001 0.3491 11758430_s_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) up 0 0.8325 ILMN_1772809 SLC4A1 up 0 0.6872 11726491_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) up 0 1.0524 11726490_a_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) up 0 0.9905 11726489_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) up 0.0033 0.8448 11730162_s_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0 1.0535 ILMN_1806349 SLC6A8 up 0 0.5827 11730163_x_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0.0003 0.8481 11716741_x_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0.0005 0.8864 11716740_a_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0.0008 0.8944 11716270_a_at SLIRP SRA stem-loop interacting RNA binding protein Cytoplasm other down 0.0087 -0.5443 ILMN_1661945 SLIRP down 0 -0.3487 11741023_a_at SMAD5 SMAD family member 5 Nucleus transcription regulator down 0.0039 -0.6835 ILMN_1674551 SMAD5 down 0.0016 -0.2372 11757679_s_at SMAD5 SMAD family member 5 Nucleus transcription regulator down 0.0128 -0.6746 11756552_a_at SMARCAD1 SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamilyNucleus a, containing DEAD/Henzyme box 1 down 0.0035 -0.7534 ILMN_1741976 SMARCAD1 down 0.0005 -0.3372 11741507_a_at SMOX spermine oxidase Cytoplasm enzyme up 0 0.9455 ILMN_1775380 SMOX updown 0 0.0003 0.4227 -0.376 11731064_a_at SMOX spermine oxidase Cytoplasm enzyme up 0.0002 0.916 11731446_s_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0001 0.9626 ILMN_1701933 SNCA up 0 0.6024 SNCA 21747756 SNCA acts as a danger-associated molecular pattern that activates the expression of TLRs to initiate the proinflammatory pathway and microglial activation. 11731448_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0002 0.6444 ILMN_1766165 SNCA up 0 0.4109 11731447_x_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0004 0.6509 11739782_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0004 0.6566 11753731_x_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0005 0.6197 11753730_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0009 0.6265 11754090_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0013 0.6606 11753974_s_at SNRPG small nuclear ribonucleoprotein polypeptide G Nucleus other down 0.0021 -0.6835 ILMN_1683562 SNRPG down 0 -0.4856 11757703_x_at SNRPG small nuclear ribonucleoprotein polypeptide G Nucleus other down 0.0106 -0.579 11730053_a_at SNX16 sorting nexin 16 unknown transporter down 0 -0.6931 ILMN_1787415 SNX16 down 0 -0.5227 11730054_s_at SNX16 sorting nexin 16 unknown transporter down 0.0001 -0.9702 11721447_at SNX4 sorting nexin 4 Cytoplasm transporter down 0.0022 -0.8192 ILMN_1738736 SNX4 down 0.0125 -0.2988 11727007_at SORT1 sortilin 1 Plasma Membrane transmembrane receptor up 0.0112 0.6429 ILMN_1707077 SORT1 up 0.0001 0.5938 11725244_a_at SPAST spastin Nucleus enzyme down 0.0327 -0.58 ILMN_1796738 SPAST down 0.0254 -0.309 11736145_a_at SPATA20 spermatogenesis associated 20 unknown other down 0.0081 -0.0453 ILMN_1687247 SPATA20 updown 0.0038 0 0.2394 -0.3303 11736293_a_at SPATS2L spermatogenesis associated, serine-rich 2-like unknown other up 0.021 0.1612 ILMN_1683678 SPATS2L up 0.0043 0.2313 11719364_a_at SPATS2L spermatogenesis associated, serine-rich 2-like unknown other up 0.028 0.2358 11721117_at SPCS3 signal peptidase complex subunit 3 homolog (S. cerevisiae) Cytoplasm peptidase down 0.0031 -0.7668 ILMN_1667707 SPCS3 down 0 -0.5811 11721115_at SPCS3 signal peptidase complex subunit 3 homolog (S. cerevisiae) Cytoplasm peptidase down 0.0043 -0.716 11746362_x_at SPNS3 spinster homolog 3 (Drosophila) unknown other up 0.0073 0.5731 ILMN_1668984 SPNS3 up 0.0037 0.1151 11744190_a_at SPNS3 spinster homolog 3 (Drosophila) unknown other up 0.0085 0.5832 11744191_x_at SPNS3 spinster homolog 3 (Drosophila) unknown other up 0.0115 0.6679 11734826_s_at SPRED1 sprouty-related, EVH1 domain containing 1 Plasma Membrane other down 0.0001 -0.675 ILMN_1804277 SPRED1 down 0.0003 -0.5492 11734824_at SPRED1 sprouty-related, EVH1 domain containing 1 Plasma Membrane other down 0.0002 -0.885 11734825_at SPRED1 sprouty-related, EVH1 domain containing 1 Plasma Membrane other down 0.0021 -0.9145 11722689_a_at SPTBN1 spectrin, beta, non-erythrocytic 1 Plasma Membrane other up 0.0009 0.8088 ILMN_1661335 SPTBN1 up 0.0037 0.3955 11716418_a_at SPTBN1 spectrin, beta, non-erythrocytic 1 Plasma Membrane other up 0.006 0.6907 11718850_a_at SRPK1 SRSF protein kinase 1 Nucleus kinase down 0.038 -0.5926 ILMN_1798804 SRPK1 down 0.0173 -0.2777 8943351 STAT1 is part of the interferon-stimulated gene factor 3 (ISGF3) transcription complex which is composed of a STAT1:2 heterodimer and a weak DNA-binding protein, IRF9. 11723038_at SRSF3 serine/arginine-rich splicing factor 3 Nucleus other down 0.0346 -0.6254 ILMN_1723212 SRSF3 down 0.0294 -0.2701 22065572 STAT1 phosphorylation at Ser708 is a key event in the IFN signalling pathway that imparts anti-viral immunity to restrict West Nile virus infection. (Demonstrated in mice) 11745822_x_at SRSF6 serine/arginine-rich splicing factor 6 Nucleus other down 0.0098 -0.3711 ILMN_1697469 SRSF6 down 0.0121 -0.3157 17971840 STAT1 mediates IFNG cytokine signalling, and as a member of the STAT family protein, STAT1 has a significant impact on the innate immunity during sepsis. 11743839_a_at ST3GAL6 ST3 beta-galactoside alpha-2,3-sialyltransferase 6 Cytoplasm enzyme down 0.001 -0.6496 ILMN_1781560 ST3GAL6 down 0 -0.7031 18678606 STAT1 serine phosphorylation is induced by TNF-alpha and PGE2 and this activates expression of the STAT1 and NF-kappaB target gene IFN regulatory factor 1 (IRF1), which contributes to IFN responses. 11726690_a_at STAT1 signal transducer and activator of transcription 1, 91kDa Nucleus transcription regulator up 0.0005 0.747 ILMN_1691364 STAT1 updown 0 0.0096 0.5955 -0.1957 STAT1 20829351 STAT1 transcription factor enhances TLR8 functionality by binding of to GAS elements on the TLR8 promoter in an IFN-gamma-dependent manner. 11726689_a_at STAT1 signal transducer and activator of transcription 1, 91kDa Nucleus transcription regulator up 0.0336 0.4042 ILMN_1777325 STAT1 up 0.0052 0.2392 16481475 Acetylation of STAT1 modulates NF-kappaB activity and thus ultimately apoptosis where, as a result, RELA DNA binding, nuclear localization, and expression of anti-apoptotic NF-kappaB target genes decrease. 11760880_a_at STAT2 signal transducer and activator of transcription 2, 113kDa Nucleus transcription regulator up 0.0149 0.7031 ILMN_1690921 STAT2 up 0.0009 0.3515 STAT2 22425562 Histone deacetylase inhibitors prevent IFNG-mediated phosphorylation of STAT1. 11720008_a_at STEAP4 STEAP family member 4 Plasma Membrane other down 0.0407 -0.4642 ILMN_1772036 STEAP4 down 0.0066 -0.3335 7657660 STAT1 phosphorylation and DNA binding activity is under the control of Janus protein-tyrosine kinases (JAKs) and the epidermal growth factor receptor (EGFR). 11732661_x_at STIL SCL/TAL1 interrupting locus Nucleus other down 0.0278 -0.6239 ILMN_1807232 STIL down 0.015 -0.2862 16689942 STAT2 is a critical transactivator component of the interferon-stimulated gene factor 3 (ISGF3) complex that drives the expression of many interferon (IFN)-inducible genes. 11726042_a_at STK17B serine/threonine kinase 17b Nucleus kinase down 0.0234 -0.7768 ILMN_1798543 STK17B down 0.0016 -0.4049 8943351 STAT2 is part of STAT-containing transcription factor, the alpha-interferon-induced ISGF3, that is composed of a STAT1:2 heterodimer and a weak DNA-binding protein, IRF9. 11726264_s_at STRADB STE20-related kinase adaptor beta Cytoplasm kinase up 0.0319 0.6543 ILMN_1701386 STRADB up 0.0001 0.5597 23391734 A loss-of-function mutation in STAT2 is associated with increased susceptibility to childhood viral diseases. 11720598_x_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0 -1.573 ILMN_1736054 SUB1 down 0 -0.6129 11758245_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0 -0.9899 11756654_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0 -1.1013 11720599_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.0021 -0.6529 11751297_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.0056 -0.6758 11716439_s_at TAF7 TAF7 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 55kDaNucleus transcription regulator down 0.0288 -0.6942 ILMN_1759460 TAF7 down 0.0031 -0.3932 20304918 TAX1BP1 and TNFAIP3 (A20) inhibit antiviral signalling by targeting TBK1/IKKi kinases and disrupting the TRAF3-TBK1-IKKi signalling complex. 11725898_s_at TAL1 T-cell acute lymphocytic leukemia 1 Nucleus transcription regulator up 0.0011 0.835 ILMN_1748450 TAL1 up 0.0258 0.2323 21765415 TAX1BP1 phosphorylation by CHUK is pivotal for the proinflammatory cytokine-dependent assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation. (Demonstrated in mouse) 11718272_a_at TAX1BP1 Tax1 (human T-cell leukemia virus type I) binding protein 1 Cytoplasm other down 0.0012 -0.7541 ILMN_1793118 TAX1BP1 down 0 -0.6008 TAX1BP1 17283140 TAX1BP1 is a nuclear receptor co-activator that forms a complex with the glucocorticoid receptor (NR3C1). TAX1BP1 can bind Tax, a human T-cell leukemia virus type 1 oncoprotein, directly and this induces the dissociation of TAX1BP1 from the glucocorticoid 11727378_at TBC1D15 TBC1 domain family, member 15 Cytoplasm other down 0.002 -0.7389 ILMN_1803941 TBC1D15 down 0.0018 -0.3692 11726124_at TCN1 transcobalamin I (vitamin B12 binding protein, R binder family) Cytoplasm transporter up 0.0218 0.4641 ILMN_1768469 TCN1 up 0.0013 0.3888 11744645_a_at TCN2 transcobalamin II Extracellular Space transporter up 0.0008 0.6732 ILMN_1740572 TCN2 up 0.0475 0.2542 11720243_x_at TCN2 transcobalamin II Extracellular Space transporter up 0.0027 0.8451 11720242_a_at TCN2 transcobalamin II Extracellular Space transporter up 0.0054 0.6022 11736608_a_at TGM3 transglutaminase 3 (E polypeptide, protein-glutamine-gamma-glutamyltransferase)Cytoplasm enzyme down 0.0011 -0.5758 ILMN_1786847 TGM3 updown 0.0013 0.0131 0.386 -0.2629 11730065_at TIGD7 tigger transposable element derived 7 unknown other down 0.0011 -0.9658 ILMN_1676905 TIGD7 down 0.0434 -0.2558 11743123_a_at TLN1 talin 1 Plasma Membrane other up 0.0002 0.8311 ILMN_1696643 TLN1 updown 0.0001 0.0005 0.6214 -0.3033 15728506 Human TLR10 is an orphan member of the TLR family with no identified specific ligand 11746406_a_at TLR10 toll-like receptor 10 Plasma Membrane transmembrane receptor down 0.0373 -0.5296 ILMN_1719905 TLR10 down 0.0174 -0.3052 TLR10 15728506 Able to homodimerize, heterodimerize with TLR1 and TLR2, and directly associate with MYD88 11731200_a_at TLR5 toll-like receptor 5 Plasma Membrane transmembrane receptor down 0.0087 -0.7251 ILMN_1722981 TLR5 updown 0.0035 0.0246 0.331 -0.2028 TLR5 11323673 TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and its activation mobilizes the nuclear factor NF-kappaB and stimulates tumour necrosis factor-alpha (TNF) production. 11721928_a_at TMCC2 transmembrane and coiled-coil domain family 2 Extracellular Space other up 0.0194 0.6285 ILMN_1659024 TMCC2 up 0.0207 0.2052 11489966 TLR5 expressed on the basolateral surface of intestinal epithelia mediates innate immune inflammatory responses to Salmonella by inducing epithelial pro-inflammatory gene expression. 11721931_s_at TMCC2 transmembrane and coiled-coil domain family 2 Extracellular Space other up 0.0307 0.6244 12794153 TLR5 forms heteromeric complexes with TLR4 as well as homomeric complexes. Signaling via heteromeric TLR5/TLR4 complexes is involved in the induction of macrophage nitric oxide (NO) production by Gram-negative flagellin. 11731401_a_at TMCO1 transmembrane and coiled-coil domains 1 unknown other down 0 -1.0172 ILMN_1793829 TMCO1 down 0 -0.7642 22434932 TLR5 forms a dimer upon binding to bacterial flagellin. 11731400_s_at TMCO1 transmembrane and coiled-coil domains 1 unknown other down 0.0001 -0.8882 22545147 TLR5 is highly expressed in mucosal dendritic cells and TLR5 signalling restricts regulatory T cell generation. (Demonstrated in mice) 11762892_at TMCO1 transmembrane and coiled-coil domains 1 unknown other down 0.0015 -0.7589 17283206 Toll-like receptor 5 (TLR5) is the TLR activated by bacterial flagellin and TLR5 residue 268 is responsible for human and mouse discrimination between flagellin molecules. 11731402_at TMCO1 transmembrane and coiled-coil domains 1 unknown other down 0.0089 -0.6073 15069060 TLR5 engagement with its ligand, flagellin, results in the activation of MAP kinases (ERK1/2, JNK, and p38) and degradation of NFKBIA (I-kappa-B-alpha). 11722392_a_at TMEM126B transmembrane protein 126B unknown other down 0.0009 -0.7817 ILMN_1766851 TMEM126B down 0 -0.5186 22863420 TLR5 deficiency in mice leads to a transient inability to manage proteobacteria which promotes chronic gut inflammation. (Demonstrated in mouse) 11752680_a_at TMEM135 transmembrane protein 135 Cytoplasm other down 0.0016 -0.7827 ILMN_1700202 TMEM135 down 0.0329 -0.2933 11725902_s_at TMEM135 transmembrane protein 135 Cytoplasm other down 0.0169 -0.7026 11745789_a_at TMEM135 transmembrane protein 135 Cytoplasm other down 0.0307 -0.6879 11751628_a_at TMEM140 transmembrane protein 140 unknown other down 0.0423 -0.5025 ILMN_1736863 TMEM140 updown 0.0085 0.0002 0.2769 -0.4386 11724275_s_at TMEM158 transmembrane protein 158 (gene/pseudogene) Plasma Membrane other up 0 1.0242 ILMN_1792455 TMEM158 updown 0 0.0133 0.8408 -0.1437 11720217_a_at TMEM176A transmembrane protein 176A unknown other updown 0.0307 0.0001 0.4238 -0.2478 ILMN_1791511 TMEM176A updown 0.0024 0 0.2321 -0.4667 11721098_x_at TMX1 thioredoxin-related transmembrane protein 1 Cytoplasm enzyme down 0.0109 -0.728 ILMN_1691181 TMX1 down 0 -0.6752 11721096_a_at TMX1 thioredoxin-related transmembrane protein 1 Cytoplasm enzyme down 0.0355 -0.6339 11743636_at TNFAIP6 tumor necrosis factor, alpha-induced protein 6 Extracellular Space other updown 0.0026 0.0011 0.6647 -0.7452 ILMN_1785732 TNFAIP6 updown 0.0004 0 0.3448 -0.4016 11738483_a_at TNFRSF13B tumor necrosis factor receptor superfamily, member 13B Plasma Membrane transmembrane receptor down 0.0421 -0.5515 ILMN_1759075 TNFRSF13B down 0.0005 -0.4583 TNFRSF13B 20676093 TNFRSF13B (TACI) triggers class-switch recombination (CSR) via the DNA-editing enzyme AID by activating NF-kappaB through a Toll-like receptor (TLR)-like MyD88-IRAK1-IRAK4-TRAF6-TAK1 pathway. 11751841_a_at TNFRSF17 tumor necrosis factor receptor superfamily, member 17 Plasma Membrane other down 0 -1.1157 ILMN_1768016 TNFRSF17 down 0 -0.4732 11743730_at TNFSF10 tumor necrosis factor (ligand) superfamily, member 10 Extracellular Space cytokine down 0.0496 -0.7145 ILMN_1801307 TNFSF10 down 0.0003 -0.3665 TNFSF10 23498957 TNFSF10 is targeted by human cytomegalovirus glycoprotein to protect infected cells from natural killer cell cytotoxicity. 11716559_x_at TNS1 tensin 1 Plasma Membrane other up 0 0.885 ILMN_1807919 TNS1 up 0 0.7235 11716558_at TNS1 tensin 1 Plasma Membrane other up 0 0.8944 11716556_a_at TNS1 tensin 1 Plasma Membrane other up 0 1.0006 11745268_a_at TNS1 tensin 1 Plasma Membrane other up 0 1.0677 11716557_a_at TNS1 tensin 1 Plasma Membrane other up 0.0139 0.6691 11743578_x_at TOMM5 translocase of outer mitochondrial membrane 5 homolog (yeast) Cytoplasm other down 0 -1.1247 ILMN_1808661 TOMM5 down 0.0007 -0.3611 11727649_a_at TOMM5 translocase of outer mitochondrial membrane 5 homolog (yeast) Cytoplasm other down 0.0001 -0.8058 11753887_x_at TOMM5 translocase of outer mitochondrial membrane 5 homolog (yeast) Cytoplasm other down 0.012 -0.6507 11720970_at TOP2A topoisomerase (DNA) II alpha 170kDa Nucleus enzyme novobiocin, etoposide,down CPI-0004Na, pixantrone, becatecarin, elsamitrucin,0.0001 AQ4N, BN 80927,-0.8125 tafluposide, ILMN_1686097 mitoxantrone,TOP2A norfloxacin, dexrazoxane,down tirapazamine, TAS-103, gatifloxacin,0.0001 valrubicin, gemifloxacin, -0.4191nemorubicin, nalidixic acid, epirubicin, doxorubicin, daunorubicin 11720971_at TOP2A topoisomerase (DNA) II alpha 170kDa Nucleus enzyme novobiocin, etoposide,down CPI-0004Na, pixantrone, becatecarin, elsamitrucin,0.0009 AQ4N, BN 80927,-0.6255 tafluposide, mitoxantrone, norfloxacin, dexrazoxane, tirapazamine, TAS-103, gatifloxacin, valrubicin, gemifloxacin, nemorubicin, nalidixic acid, epirubicin, doxorubicin, daunorubicin 11734051_a_at TRAT1 T cell receptor associated transmembrane adaptor 1 Plasma Membrane kinase down 0.0013 -0.7675 ILMN_1684943 TRAT1 down 0.0114 -0.3289 TRAT1 21074459 TRAT1 (TRIM56) is an interferon-inducible E3 ubiquitin ligase that modulates TMEM173 (STING) to confer double-stranded DNA-mediated innate immune responses. 11734050_a_at TRAT1 T cell receptor associated transmembrane adaptor 1 Plasma Membrane kinase down 0.0442 -0.6032 11718280_s_at TRIAP1 TP53 regulated inhibitor of apoptosis 1 Cytoplasm other down 0.0141 -0.606 ILMN_1774083 TRIAP1 down 0.0367 -0.3326 11731997_at TRIM58 tripartite motif containing 58 unknown other up 0 0.9646 ILMN_1705458 TRIM58 up 0.0013 0.204 TRIM58 23438823 TRIM58 was identified in a systematic screen for positive regulators of innate immune responses. 11731996_at TRIM58 tripartite motif containing 58 unknown other up 0 0.8292 11731525_at TRIP13 thyroid hormone receptor interactor 13 Cytoplasm transcription regulator down 0.047 -0.6295 ILMN_1796589 TRIP13 down 0.0387 -0.2198 11758210_s_at TRMT10C tRNA methyltransferase 10 homolog C (S. cerevisiae) Cytoplasm other down 0.0144 -0.6821 ILMN_1672565 TRMT10C down 0.022 -0.282 11722902_a_at TRMT13 tRNA methyltransferase 13 homolog (S. cerevisiae) unknown other down 0.0008 -0.8116 ILMN_1659786 TRMT13 down 0 -0.607 11745452_a_at TRMT13 tRNA methyltransferase 13 homolog (S. cerevisiae) unknown other down 0.0422 -0.6019 11736176_a_at TRNT1 tRNA nucleotidyl transferase, CCA-adding, 1 Cytoplasm enzyme down 0.0021 -0.783 ILMN_1655924 TRNT1 down 0.0088 -0.321 11722543_at TRPC1 transient receptor potential cation channel, subfamily C, member 1 Plasma Membrane ion channel down 0.0296 -0.673 ILMN_1674380 TRPC1 down 0.0431 -0.2692 11749969_a_at TSPAN5 tetraspanin 5 Plasma Membrane other up 0.0051 0.6862 ILMN_1799028 TSPAN5 up 0.0001 0.4586 11715469_s_at TXN thioredoxin Cytoplasm enzyme down 0 -1.0334 ILMN_1680314 TXN down 0 -0.5762 11753804_x_at TXN thioredoxin Cytoplasm enzyme down 0.0003 -0.9481 11753775_x_at TXN thioredoxin Cytoplasm enzyme down 0.0007 -0.8765 11715470_x_at TXN thioredoxin Cytoplasm enzyme down 0.0017 -0.9584 11750538_x_at TXN thioredoxin Cytoplasm enzyme down 0.004 -0.8508 11757541_x_at TXNDC17 thioredoxin domain containing 17 Cytoplasm enzyme down 0.0141 -0.6184 ILMN_1659437 TXNDC17 down 0 -0.5324 11754067_a_at TXNDC9 thioredoxin domain containing 9 unknown other down 0 -0.9345 ILMN_1731137 TXNDC9 down 0.0002 -0.3978 11759710_at TXNDC9 thioredoxin domain containing 9 unknown other down 0.0001 -0.8797 11744784_a_at TXNDC9 thioredoxin domain containing 9 unknown other down 0.001 -0.8686 11731479_s_at TXNDC9 thioredoxin domain containing 9 unknown other down 0.0011 -0.8099 11730895_at UBA6 ubiquitin-like modifier activating enzyme 6 Cytoplasm enzyme down 0.0007 -0.8577 ILMN_1675085 UBA6 down 0.0016 -0.3562 11728225_at UBE2J1 ubiquitin-conjugating enzyme E2, J1 Cytoplasm enzyme down 0.047 -0.5633 ILMN_1713759 UBE2J1 down 0.0014 -0.3379 11753695_s_at UBE2N ubiquitin-conjugating enzyme E2N Cytoplasm enzyme down 0.0393 -0.516 ILMN_1793651 UBE2N down 0.0004 -0.4916 UBE2N 16862162 UBE2N abalation resulted in defective B cell development and in impaired B cell and macrophage activation. 11759770_a_at UCHL5 ubiquitin carboxyl-terminal hydrolase L5 Cytoplasm peptidase down 0.0003 -0.9446 ILMN_1731612 UCHL5 down 0.004 -0.3123 11759771_x_at UCHL5 ubiquitin carboxyl-terminal hydrolase L5 Cytoplasm peptidase down 0.0114 -0.6188 11742854_x_at UGDH UDP-glucose 6-dehydrogenase Nucleus enzyme down 0.0416 -0.5871 ILMN_1729563 UGDH down 0.0005 -0.4685 11723192_a_at UHRF1 ubiquitin-like with PHD and ring finger domains 1 Nucleus transcription regulator down 0.0287 -0.1666 ILMN_1786065 UHRF1 down 0.0171 -0.2428 11733901_a_at UQCRQ ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5kDa Cytoplasm enzyme down 0 -1.032 ILMN_1666471 UQCRQ down 0 -1.1707 11717778_at USP15 ubiquitin specific peptidase 15 Cytoplasm peptidase down 0.033 -0.6211 ILMN_1665557 USP15 down 0 -0.5953 ILMN_1867588 USP15 down 0.0222 -0.2888 11725415_a_at USP16 ubiquitin specific peptidase 16 Cytoplasm peptidase down 0.0065 -0.6951 ILMN_1815407 USP16 down 0.0415 -0.2581 11735118_at VAMP4 vesicle-associated membrane protein 4 Cytoplasm other down 0.0001 -0.8768 ILMN_1664175 VAMP4 down 0.028 -0.341 11757701_s_at VAMP4 vesicle-associated membrane protein 4 Cytoplasm other down 0.001 -0.67 11749619_a_at VBP1 von Hippel-Lindau binding protein 1 Cytoplasm other down 0.0003 -0.8214 ILMN_1800612 VBP1 down 0 -0.6221 11743605_s_at VBP1 von Hippel-Lindau binding protein 1 Cytoplasm other down 0.0183 -0.6537 11746356_a_at VNN2 vanin 2 unknown enzyme down 0.0013 -0.67 ILMN_1758864 VNN2 down 0.0173 -0.2448 11741768_a_at VNN2 vanin 2 unknown enzyme down 0.0474 -0.495 11728722_s_at VPS29 vacuolar protein sorting 29 homolog (S. cerevisiae) Cytoplasm transporter down 0.0406 -0.6328 ILMN_1704619 VPS29 down 0.0083 -0.2946 11751281_a_at VWCE von Willebrand factor C and EGF domains unknown other up 0 0.7813 ILMN_1760315 VWCE up 0 0.5346 11756497_a_at VWCE von Willebrand factor C and EGF domains unknown other up 0.0001 0.6993 11747666_a_at WARS tryptophanyl-tRNA synthetase Cytoplasm enzyme up 0 0.9002 ILMN_1727271 WARS up 0 0.8094 11726286_a_at WARS tryptophanyl-tRNA synthetase Cytoplasm enzyme up 0.0002 0.6871 11726287_a_at WARS tryptophanyl-tRNA synthetase Cytoplasm enzyme up 0.002 0.7151 11722218_a_at WBP4 WW domain binding protein 4 (formin binding protein 21) Cytoplasm other down 0.0483 -0.6664 ILMN_1697906 WBP4 down 0.0291 -0.2429 11743470_a_at WDFY3 WD repeat and FYVE domain containing 3 Cytoplasm enzyme up 0.0321 0.583 ILMN_1697493 WDFY3 up 0.0006 0.4559 11718761_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.0001 -0.7786 ILMN_1660549 WLS down 0.0007 -0.3192 11745018_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.0001 -0.4934 11718760_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.0007 -0.6058 11733513_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.0041 -0.5604 11743281_a_at WNK1 WNK lysine deficient protein kinase 1 Cytoplasm kinase up 0.0042 0.7381 ILMN_1876924 WNK1 up 0.0057 0.4273 11747631_x_at XAF1 XIAP associated factor 1 Nucleus other up 0.0087 0.5111 ILMN_1742618 XAF1 updown 0.0005 0.0003 0.2558 -0.3019 11749370_x_at XAF1 XIAP associated factor 1 Nucleus other up 0.0225 0.4762 11747630_a_at XAF1 XIAP associated factor 1 Nucleus other up 0.0271 0.4204 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase down 0.036 -0.5602 ILMN_1767481 XRCC6BP1 down 0.0015 -0.3587 11719415_a_at YES1 v-yes-1 Yamaguchi sarcoma viral oncogene homolog 1 Cytoplasm kinase dasatinib down 0.0212 -0.6716 ILMN_1691466 YES1 down 0.0343 -0.2496 11721521_at ZDHHC17 zinc finger, DHHC-type containing 17 Cytoplasm enzyme down 0.0017 -0.8369 ILMN_1697153 ZDHHC17 down 0 -0.6687 Page 91 of 111 Diabetes

11721520_at ZDHHC17 zinc finger, DHHC-type containing 17 Cytoplasm enzyme down 0.0125 -0.6985 11747837_a_at ZFAND1 zinc finger, AN1-type domain 1 unknown other down 0.0046 -0.8336 ILMN_1730907 ZFAND1 down 0.0003 -0.4724 11754534_a_at ZFYVE16 zinc finger, FYVE domain containing 16 Nucleus transporter down 0.024 -0.6185 ILMN_1651769 ZFYVE16 down 0.021 -0.228 11734342_a_at ZMYM1 zinc finger, MYM-type 1 unknown other down 0.0001 -1.0644 ILMN_1702763 ZMYM1 down 0 -0.556 11751981_a_at ZMYM1 zinc finger, MYM-type 1 unknown other down 0.0016 -0.8463 11739953_at ZNF14 zinc finger protein 14 Nucleus transcription regulator down 0.0142 -0.6975 ILMN_1692145 ZNF14 down 0.002 -0.2825 11743021_a_at ZNF195 zinc finger protein 195 Nucleus other down 0.0029 -0.7245 ILMN_1688515 ZNF195 down 0.0188 -0.266 11759422_x_at ZNF195 zinc finger protein 195 Nucleus other down 0.011 -0.7567 11743149_at ZNF22 zinc finger protein 22 Nucleus other down 0.0039 -0.8607 ILMN_1798533 ZNF22 updown 0.0249 0 0.2215 -0.6774 11727704_a_at ZNF439 zinc finger protein 439 Nucleus other down 0.011 -0.6408 ILMN_1792972 ZNF439 down 0.0003 -0.5086 11754542_x_at ZNF594 zinc finger protein 594 unknown other down 0.0005 -0.8282 ILMN_1726199 ZNF594 down 0.0038 -0.3384 11755658_x_at ZNF594 zinc finger protein 594 unknown other down 0.0068 -0.7084 11747001_a_at ZNF615 zinc finger protein 615 Nucleus other down 0.0276 -0.6099 ILMN_1672135 ZNF615 down 0.0052 -0.4029 11728910_a_at ZNF615 zinc finger protein 615 Nucleus other down 0.0323 -0.5924 11729261_a_at ZNF644 zinc finger protein 644 Nucleus other down 0.0023 -0.7824 ILMN_1730118 ZNF644 down 0.0469 -0.271 11729516_a_at ZNF644 zinc finger protein 644 Nucleus other down 0.0064 -0.6598 11729517_a_at ZNF644 zinc finger protein 644 Nucleus other down 0.0075 -0.7788 11724388_at ZNF721 zinc finger protein 721 unknown other down 0.0354 -0.5939 ILMN_1805271 ZNF721 down 0.0002 -0.4481 11729465_x_at ZNF816 zinc finger protein 816 unknown other down 0.001 -0.8484 ILMN_1728710 ZNF816 down 0 -0.5613 11744712_a_at ZNF823 zinc finger protein 823 Nucleus other down 0.0063 -0.6872 ILMN_1669064 ZNF823 down 0.0093 -0.3768 11739988_a_at ZNF823 zinc finger protein 823 Nucleus other down 0.0347 -0.5377 11744054_a_at ZNFX1 zinc finger, NFX1-type containing 1 Nucleus transcription regulator up 0.0189 0.7191 ILMN_1745148 ZNFX1 up 0.0001 0.5135 11722793_a_at ZNHIT3 zinc finger, HIT-type containing 3 Nucleus transcription regulator down 0.0076 -0.6446 ILMN_1812478 ZNHIT3 down 0 -0.5493 11728652_x_at ZRANB2 zinc finger, RAN-binding domain containing 2 Nucleus transcription regulator down 0.0075 -0.7628 ILMN_1662383 ZRANB2 down 0 -0.6793 Diabetes Page 92 of 111

Differentially expressed genes 1-2 years before T1D diagnosis (FDR < 0.05) showing concordant changes in Affymetrix and Illumina arrays, and information regarding the innate immunity function of the genes (InnateDB)

AFFYMETRIX Case vs. control ILLUMINA Case vs. control InnateDB (www.innatedb.org) Innate Immunity Genes in human. P value for overlap is 0.0000000004. Affymetrix ID Gene Symbol (IPA) Gene name (IPA) Location (IPA) Type (IPA) Drug (IPA) Change probeset FDR max FDR min SLR max SLR min Illumina ID Gene Symbol (IPA) Change probeFDR max FDR min SLR max SLR min Gene Symbol (human)Pubmed ID Annotation 11736635_a_at AAK1 AP2 associated kinase 1 Cytoplasm kinase up 0.0182 0.3978 ILMN_1688755 AAK1 up 0.0027 0.3583 11747858_a_at ABCE1 ATP-binding cassette, sub-family E (OABP), member 1 Cytoplasm transporter down 0.0485 -0.4051 ILMN_1676846 ABCE1 down 0.0466 -0.241 11730238_a_at ABHD10 abhydrolase domain containing 10 Cytoplasm enzyme down 0.0087 -0.6043 ILMN_1770031 ABHD10 down 0.016 -0.1861 11746269_a_at ABHD3 abhydrolase domain containing 3 unknown enzyme down 0.0079 -0.6394 ILMN_1801767 ABHD3 down 0.003 -0.3257 11730887_a_at ACOT11 acyl-CoA thioesterase 11 Cytoplasm enzyme up 0.0494 0.3598 ILMN_1739594 ACOT11 updown 0.006 0.0344 0.1825 -0.2796 11754458_a_at ACRBP acrosin binding protein Extracellular Space other up 0.013 0.4506 ILMN_1784203 ACRBP up 0.0006 0.2622 11750700_a_at ACSL1 acyl-CoA synthetase long-chain family member 1 Cytoplasm enzyme updown 0.0308 0 0.4268 -0.6475 ILMN_1684585 ACSL1 updown 0 0.001 0.281 -0.3362 11721452_a_at ACTR6 ARP6 actin-related protein 6 homolog (yeast) unknown transporter down 0.0004 -0.4726 ILMN_1697585 ACTR6 down 0 -0.3352 11763740_a_at ACTR6 ARP6 actin-related protein 6 homolog (yeast) unknown transporter down 0.0312 -0.3713 11739021_a_at ADAR adenosine deaminase, RNA-specific Nucleus enzyme up 0.037 0.3516 ILMN_1776777 ADAR up 0.0172 0.2166 ADAR 21809195 ADAR destabalizes RNA structure by the deamination of adenosine to inosine, and therefore is able to disrupt replication of dsRNA viruses in the host. 11758757_at ADH5 alcohol dehydrogenase 5 (class III), chi polypeptide Cytoplasm enzyme down 0.0323 -0.465 ILMN_1738604 ADH5 down 0.0005 -0.3919 11756406_x_at ADM adrenomedullin Extracellular Space other updown 0.0041 0 0.4193 -0.7958 ILMN_1708934 ADM updown 0.0006 0 0.1699 -0.4708 11716710_a_at ADM adrenomedullin Extracellular Space other updown 0.0209 0.0002 0.3306 -0.6743 11753618_a_at ADM adrenomedullin Extracellular Space other down 0.0161 -0.4486 11718997_at AHSP alpha hemoglobin stabilizing protein Cytoplasm other up 0.0003 0.5299 ILMN_1696512 AHSP updown 0.0044 0.0315 0.2318 -0.0598 11723804_a_at AKAP12 A kinase (PRKA) anchor protein 12 Cytoplasm transporter down 0.0202 -0.2988 ILMN_1686846 AKAP12 down 0.0089 -0.0971 11715711_a_at AKR1C3 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase,Cytoplasm type II) enzyme updown 0.0297 0 0.4434 -0.6001 ILMN_1713124 AKR1C3 updown 0.0057 0.0007 0.3008 -0.3109 11758412_s_at ALAS2 aminolevulinate, delta-, synthase 2 Cytoplasm enzyme up 0.0146 0.5023 ILMN_1708323 ALAS2 up 0.0072 0.2886 11734745_a_at ALAS2 aminolevulinate, delta-, synthase 2 Cytoplasm enzyme up 0.0241 0.3534 11716184_s_at ALCAM activated leukocyte cell adhesion molecule Plasma Membrane other down 0.0021 -0.486 ILMN_1670870 ALCAM down 0.008 -0.3 11716182_s_at ALCAM activated leukocyte cell adhesion molecule Plasma Membrane other down 0.0163 -0.5479 11748031_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase updown 0 0.001 0.7254 -0.3948 ILMN_1701603 ALPL updown 0 0 0.707 -0.1758 11748032_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase updown 0 0.0016 0.6371 -0.2948 11750919_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase updown 0 0.0016 0.3761 -0.3952 11729337_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase updown 0 0.0027 0.6782 -0.2613 11729336_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase updown 0 0.004 0.6776 -0.3523 11746965_a_at ANPEP alanyl (membrane) aminopeptidase Plasma Membrane peptidase up 0.037 0.3741 ILMN_1763837 ANPEP up 0 0.511 11756334_x_at ANXA3 annexin A3 Cytoplasm enzyme updown 0.0002 0 0.5323 -1.3269 ILMN_1694548 ANXA3 updown 0.0066 0.0033 0.1868 -0.3333 11724283_a_at ANXA3 annexin A3 Cytoplasm enzyme updown 0.0003 0 0.5141 -1.0925 11727629_at APBA2 amyloid beta (A4) precursor protein-binding, family A, member 2 Cytoplasm transporter up 0.023 0.3716 ILMN_1723626 APBA2 up 0.0004 0.2457 11740441_a_at APOBEC3A apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A Cytoplasm enzyme down 0.0137 -0.3898 ILMN_1680192 APOBEC3A updown 0.0029 0.0009 0.2346 -0.3593 APOBEC3A 20615867 APOBEC3A has deaminase activity in monocytes and macrophages and this induces high levels of TC-specific deaminase activity in IFN-alpha signalling. 11725701_a_at AQP9 aquaporin 9 Plasma Membrane transporter down 0.0012 -0.5202 ILMN_1715068 AQP9 updown 0.0004 0.0002 0.3461 -0.4128 11749906_a_at AQP9 aquaporin 9 Plasma Membrane transporter down 0.0083 -0.4828 11731404_at ATP6V1G1 ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G1 Cytoplasm transporter up 0.0115 0.4929 ILMN_1784523 ATP6V1G1 updown 0.0021 0 0.2633 -0.3919 11728909_s_at B3GALTL beta 1,3-galactosyltransferase-like unknown other down 0.0294 -0.3405 ILMN_1764813 B3GALTL down 0.0008 -0.328 11746692_a_at BAZ1A bromodomain adjacent to zinc finger domain, 1A Nucleus other down 0.0127 -0.5878 ILMN_1742230 BAZ1A updown 0.0466 0.0058 0.1983 -0.3345 11728355_at BBS10 Bardet-Biedl syndrome 10 unknown other down 0.0129 -0.4018 ILMN_1741985 BBS10 down 0.0003 -0.3379 11720566_at BCAT1 branched chain amino-acid transaminase 1, cytosolic Cytoplasm enzyme down 0.0151 -0.4194 ILMN_1766169 BCAT1 down 0.0114 -0.2542 11730096_a_at BCL2A1 BCL2-related protein A1 Cytoplasm other updown 0.0062 0 0.6228 -1.0499 ILMN_1769229 BCL2A1 updown 0.0126 0.0084 0.1971 -0.2721 BCL2A1 21167304 BCL2A1 negatively regulates autophagy and expression of BCL2A1 in Mycobacterium tuberculosis infected macrophages provides the bacteria a survival strategy to overcome host defences. 11759322_at BCL6 B-cell CLL/lymphoma 6 Nucleus transcription regulator updown 0.0409 0.0049 0.224 -0.5244 ILMN_1737314 BCL6 updown 0.0226 0.0019 0.1222 -0.2884 11739841_a_at BCL6 B-cell CLL/lymphoma 6 Nucleus transcription regulator down 0.0027 -0.6432 ILMN_1746053 BCL6 up 0.0363 0.2403 11750749_a_at BCL6 B-cell CLL/lymphoma 6 Nucleus transcription regulator down 0.0031 -0.5907 11727525_a_at C12orf29 chromosome 12 open reading frame 29 unknown other down 0.0277 -0.4485 ILMN_1792671 C12orf29 down 0.0098 -0.3306 11716875_at C14orf142 chromosome 14 open reading frame 142 unknown other down 0.025 -0.4164 ILMN_1685781 C14orf142 down 0.0273 -0.2528 11743264_x_at C14orf2 chromosome 14 open reading frame 2 Cytoplasm other updown 0.0156 0.0022 0.2067 -0.6515 ILMN_1652722 C14orf2 updown 0.0353 0.0017 0.1744 -0.3059 11758135_s_at C14orf2 chromosome 14 open reading frame 2 Cytoplasm other down 0.0377 -0.568 11725889_at C19orf59 chromosome 19 open reading frame 59 unknown other down 0 -0.8781 ILMN_1762713 C19orf59 updown 0.0057 0 0.0048 -0.8498 11725888_at C19orf59 chromosome 19 open reading frame 59 unknown other down 0 -0.8229 11726810_s_at C19orf77 chromosome 19 open reading frame 77 unknown other up 0.0033 0.3976 ILMN_1774375 C19orf77 up 0.0031 0.2138 11743934_a_at C1GALT1C1 C1GALT1-specific chaperone 1 Cytoplasm enzyme down 0.0012 -0.5823 ILMN_1751234 C1GALT1C1 down 0.0003 -0.4541 11726618_a_at C1GALT1C1 C1GALT1-specific chaperone 1 Cytoplasm enzyme down 0.0069 -0.4079 11726619_s_at C1GALT1C1 C1GALT1-specific chaperone 1 Cytoplasm enzyme down 0.0214 -0.5726 11742700_s_at C1R complement component 1, r subcomponent Extracellular Space peptidase SERPING1 down 0.0243 -0.4562 ILMN_1683687 C1R down 0.0287 -0.2616 C1R 11445589 C1R is the protease that mediates activation of the classical complement C1 complex and this catalytic property is mediated by C1R C-terminal region, comprising two complement control protein (CCP) modules followed by a serine protease (SP) domain. 11717045_a_at C2 complement component 2 Extracellular Space peptidase up 0.0086 0.479 ILMN_1710740 C2 up 0.0063 0.2534 C2 12791093 C2 is part of the classical and lectin complement pathways 11757208_s_at C22orf34 chromosome 22 open reading frame 34 unknown other up 0.0028 0.6657 ILMN_1911927 C22orf34 up 0.0003 0.3609 11044372 C2 molecule binds to C4B and is cleaved by C1S protease into C2A and C2B fragments and the resulting C4B2A complex (C3 convertase) is the active protease which cleaves C3 ILMN_1717371 C22orf34 up 0.0004 0.2351 11755573_s_at C5orf4 chromosome 5 open reading frame 4 unknown other updown 0 0.0003 0.8731 -0.2505 ILMN_1728742 C5orf4 updown 0.0016 0.0347 0.2677 0.0271 11751501_a_at C5orf4 chromosome 5 open reading frame 4 unknown other updown 0 0.0006 0.7837 0.0018 11748570_a_at C5orf4 chromosome 5 open reading frame 4 unknown other updown 0 0.0021 0.5187 -0.1226 22031815 LL-37 (CAMP) reduces influenza A viral load and disease severity in mice. 11759232_at C6orf25 chromosome 6 open reading frame 25 Plasma Membrane other down 0.0001 -0.4778 ILMN_1709799 C6orf25 down 0.0051 -0.1552 21832078 CAMP expression is induced upon endoplasmic reticulum stress via NF-kB-C/EBP-alpha activation. 11718604_a_at C7orf41 chromosome 7 open reading frame 41 unknown other up 0.0325 0.42 ILMN_1672605 C7orf41 up 0.003 0.2345 21448240 CAMP (LL-37), at sufficiently low concentrations, is able to reduce fungal infectivity by inhibiting C. albicans adhesion to plastic surfaces, oral epidermoid cells, and the urinary bladders of female mice. The inhibitory effects of LL-37 on cell adhesion 11720531_at C9orf72 chromosome 9 open reading frame 72 unknown other down 0.0062 -0.5544 ILMN_1741881 C9orf72 updown 0.0074 0.0003 0.2837 -0.4278 21562230 CAMP (LL-37) confers protective immunity against psoriasis by neutralizing cytosolic DNA in keratinocytes and blocking the formation of AIM2 inflammasomes. 11720532_s_at C9orf72 chromosome 9 open reading frame 72 unknown other down 0.0071 -0.6096 21762664 CAMP protects against colitis induction in mice. The increased expression of CAMP in monocytes involves the activation of TLR9/ERK signalling pathway by bacterial DNA. (Demonstrated in mouse) 11758239_s_at C9orf72 chromosome 9 open reading frame 72 unknown other down 0.0118 -0.6274 23328115 CAMP (LL-37) is downregulated during septic shock. 11733115_a_at CA2 carbonic anhydrase II Cytoplasm enzyme methazolamide, hydrochlorothiazide,up acetazolamide,0.0294 trichloromethiazide, dorzolamide,0.4517 chlorothiazide,ILMN_1662795 dorzolamide/timolol,CA2 brinzolamide, chlorthalidone,updown benzthiazide,0.0014 sulfacetamide, 0.0171 topiramate 0.319 -0.0548 21464330 CAMP (LL-37) translocates across the E. coli outer membrane and halts bacterial growth by interfering cell wall biogenesis. 11730973_a_at CA4 carbonic anhydrase IV Plasma Membrane enzyme methazolamide, hydrochlorothiazide,up acetazolamide,0.0167 trichloromethiazide, chlorothiazide,0.448 chlorthalidone,ILMN_1695157 benzthiazide,CA4 sulfacetamide, topiramateup 0 0.2657 19625657 CAMP represents a potent antimicrobial and cell-stimulating agent, most abundantly expressed in peripheral organs such as lung and skin during inflammation. 11742124_a_at CACNG6 calcium channel, voltage-dependent, gamma subunit 6 Plasma Membrane ion channel updown 0 0.0473 0.7018 -0.0767 ILMN_1779043 CACNG6 updown 0.0012 0.0256 0.2843 -0.1667 19748465 CAMP, a protein that has direct antimicrobial activity, serves as a mediator of vitamin D3-induced autophagy. 11726688_at CAMP cathelicidin antimicrobial peptide Cytoplasm other down 0.0021 -0.2754 ILMN_1688580 CAMP updown 0.0007 0 0.2507 -0.3559 CAMP 19812202 CAMP (LL-37) modulates IFN-gamma responses during both the innate and adaptive phases of immune responses, indicating an immunomodulatory role for this endogenous peptide. 11739007_at CAPZA1 capping protein (actin filament) muscle Z-line, alpha 1 Cytoplasm other down 0.0027 -0.6086 ILMN_1803742 CAPZA1 updown 0 0.0453 0.3268 -0.3374 18397922 CAMP induces endothelium-dependent relaxation in human omental veins, or vasodilation, mediated via an effect on endothelial ALX. 11739008_x_at CAPZA1 capping protein (actin filament) muscle Z-line, alpha 1 Cytoplasm other down 0.0248 -0.5083 18923446 CAMP is involved in various aspects of skin biology, including protection against infection, wound healing, and also in psoriasis where it suppresses apoptosis in keratinocytes. 11750192_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0003 -0.682 ILMN_1768870 CAPZA2 down 0 -0.2947 20036634 CAMP has dual function as an antimicrobial agent against bacterial target cells and a cell penetrating peptide that can deliver nucleic acids into the host cells. 11723012_a_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0003 -0.7243 19797203 CAMP has both antimicrobial and regenerative capabilities and promotes high glucose-attenuated epithelial wound healing via EGFR transactivation in organ cultured corneas. 11723013_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0003 -0.7702 20163451 CAMP decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs) and this inhibition is dependent on phosphorylation of extracellular signal-regulated kinase (ERK). Vitamin C attenuates ERK signalling to inhibit the regulat 11747046_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0011 -0.6756 20190140 CAMP and human beta-defensins (hBDs) antimicrobial peptides induce the secretion of a pruritogenic cytokine IL-31 by human mast cells. 11717805_a_at CASP3 caspase 3, apoptosis-related cysteine peptidase Cytoplasm peptidase IDN-6556 down 0.0033 -0.4909 ILMN_1756787 CASP3 down 0.0002 -0.3107 21441450 CAMP (LL-37) dramatically reduced TNFA and nitric oxide levels produced by LPS and IFNG-polarized M1 macrophages, in addition LL-37-treated M1 macrophages were more efficient at suppressing tumour growth in vitro. This demonstrates the selective ability o 11719839_a_at CASP3 caspase 3, apoptosis-related cysteine peptidase Cytoplasm peptidase IDN-6556 down 0.0259 -0.4648 20610648 CAMP (LL37) directs macrophage differentiation toward macrophages with a pro-inflammatory signature and this requires internalization of the peptide, resulting in low production of IL-10 and profound production of IL-12p40 upon LPS stimulation. 11731726_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase updown 0.0005 0 0.37 -1.1234 ILMN_1722158 CASP5 updown 0 0.0002 0.2148 -0.2952 19703986 CAMP (LL37) converts self-RNA into a trigger of TLR7 and TLR8 in human dendritic cells (DC), leading to production of TNF-alpha and IL6 and the differentiation of myeloid DCs into mature DCs. 11731727_x_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase updown 0.0002 0 0.5477 -0.9819 21393634 CAMP (LL-37) attenuates lethal sepsis/endotoxin shock by suppressing the LPS-induced apoptosis of vascular and hepatic endothelial cells. LL-37 was found to inhibit the binding of LPS to the LPS receptors expressed on the cells. 11753343_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase updown 0 0 0.5336 -0.8655 21389264 CAMP (LL37) is found in high concentrations within neutrophil extracellular traps (NETs). CAMP is a neutrophil protein that facilitates the uptake and recognition of mammalian DNA by plasmacytoid dendritic cells, and may play a role in Systemic Lupus Erth 11744835_s_at CBS cystathionine-beta-synthase Cytoplasm enzyme up 0.0099 0.4017 ILMN_1804735 CBS up 0 0.3283 20042575 CAMP enhances delivery of CpG oligodeoxynucleotides to stimulate immune cells and this is independent of its amphipathic structure and its bactericidal property. 11744286_s_at CBS cystathionine-beta-synthase Cytoplasm enzyme up 0.0304 0.4051 11728027_x_at CCDC58 coiled-coil domain containing 58 Cytoplasm other up 0.0083 0.3821 ILMN_1686920 CCDC58 up 0 0.2133 11758576_s_at CCDC59 coiled-coil domain containing 59 unknown other down 0.0292 -0.4051 ILMN_1662318 CCDC59 down 0.0053 -0.3691 11744442_at CCDC82 coiled-coil domain containing 82 unknown other down 0 -0.6428 ILMN_1791933 CCDC82 down 0 -0.3342 11736416_s_at CCDC82 coiled-coil domain containing 82 unknown other down 0 -0.7711 11744443_x_at CCDC82 coiled-coil domain containing 82 unknown other down 0.0009 -0.6814 11744660_s_at CCL4L1/CCL4L2 chemokine (C-C motif) ligand 4-like 1 Plasma Membrane other up 0 0.4363 ILMN_1716276 CCL4L1/CCL4L2 updown 0.0012 0.0224 0.3006 -0.2274 11728039_s_at CCL8 chemokine (C-C motif) ligand 8 Extracellular Space cytokine up 0.004 0.1984 ILMN_1772964 CCL8 up 0 0.2795 11747113_a_at CD160 CD160 molecule Plasma Membrane transmembrane receptor down 0 -0.7235 ILMN_1742001 CD160 down 0.0003 -0.3291 11735864_a_at CD160 CD160 molecule Plasma Membrane transmembrane receptor down 0.0001 -0.5856 11729741_x_at CD68 CD68 molecule Plasma Membrane other up 0.0297 0.2441 ILMN_1714861 CD68 up 0.0009 0.2072 11763509_at CD9 CD9 molecule Plasma Membrane other up 0.0001 0.7002 ILMN_1904242 CD9 up 0.0136 0.1746 11763854_a_at CD9 CD9 molecule Plasma Membrane other up 0.0021 0.5595 11715568_a_at CD9 CD9 molecule Plasma Membrane other up 0.0094 0.5216 11715570_x_at CD9 CD9 molecule Plasma Membrane other up 0.0199 0.386 11715569_at CD9 CD9 molecule Plasma Membrane other up 0.022 0.4077 11760080_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other updown 0.0216 0.0348 0.3577 -0.2596 ILMN_1716815 CEACAM1 updown 0.0005 0 0.1511 -0.4134 CEACAM1 18836450 CEACAM1 inhibits TLR2 induced pro-inflammatory immune responses by inducing PTPN6-(SHP-1)-mediated inhibition of the PI3K-NF-kappaB signal transduction pathway in pulmonary epithelial cells. 11756058_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0 -0.7924 ILMN_1664330 CEACAM1 updown 0.0305 0.0003 0.1597 -0.3779 11723282_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0 -0.7339 11751094_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0001 -0.6391 11760081_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0001 -0.6457 11751217_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0003 -0.6543 11723283_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0003 -0.4593 11751095_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0009 -0.5942 11753506_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0009 -0.5312 11762911_x_at CEACAM3 carcinoembryonic antigen-related cell adhesion molecule 3 unknown other down 0.0373 -0.525 ILMN_1743570 CEACAM3 down 0.0003 -0.41 11758685_s_at CEACAM8 carcinoembryonic antigen-related cell adhesion molecule 8 Plasma Membrane other down 0 -0.6491 ILMN_1806056 CEACAM8 down 0.007 -0.2441 11750177_x_at CEACAM8 carcinoembryonic antigen-related cell adhesion molecule 8 Plasma Membrane other down 0 -0.61 11734346_at CEBPE CCAAT/enhancer binding protein (C/EBP), epsilon Nucleus transcription regulator up 0 0.7045 ILMN_1779095 CEBPE up 0.0004 0.3413 CEBPE 21326902 CEBPE is a member of the CCAAT enhancer binding protein family and is a transcriptional factor regulating genes in innate immunity and inflammation. The activities of CEBP are regulated via methylation of arginine and lysine side chains. 11728857_at CEP19 centrosomal protein 19kDa unknown other down 0.0402 -0.5194 ILMN_1873107 CEP19 updown 0.0473 0.003 0.0639 -0.2302 11720247_a_at CEP55 centrosomal protein 55kDa Cytoplasm other down 0.0006 -0.4857 ILMN_1747016 CEP55 down 0.0019 -0.2775 11758261_s_at CEP55 centrosomal protein 55kDa Cytoplasm other down 0.0015 -0.4391 11759323_at CEP85L centrosomal protein 85kDa-like Cytoplasm other down 0.049 -0.3657 ILMN_1855286 CEP85L down 0.0002 -0.3817 11725980_at CFD complement factor D (adipsin) Extracellular Space peptidase down 0 -0.2821 ILMN_1777190 CFD updown 0.0005 0 0.075 -0.2959 11733638_at CHM choroideremia (Rab escort protein 1) Cytoplasm enzyme down 0.0006 -0.7421 ILMN_1771238 CHM down 0.0368 -0.2823 11721504_a_at CKLF chemokine-like factor Extracellular Space cytokine down 0.0171 -0.5927 ILMN_1712389 CKLF updown 0.0089 0 0.2072 -0.4603 11727473_at CLC Charcot-Leyden crystal protein Cytoplasm enzyme up 0.0009 0.4761 ILMN_1654875 CLC updown 0 0.0002 0.3414 -0.1892 11745500_a_at CLEC10A C-type lectin domain family 10, member A Plasma Membrane other up 0.0085 0.3863 ILMN_1653166 CLEC10A up 0.0029 0.1339 11753241_s_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other updown 0.0079 0.008 0.222 -0.371 ILMN_1663142 CLEC12A updown 0 0.0027 0.0929 -0.2539 11762101_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other up 0.0082 0.2454 11729479_a_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other up 0.0305 0.2284 11721302_a_at CLEC2B C-type lectin domain family 2, member B Plasma Membrane other up 0 0.7405 ILMN_1784608 CLEC2B up 0.0396 0.1156 11724885_at CLIC3 chloride intracellular channel 3 Nucleus ion channel up 0.0036 0.6329 ILMN_1796423 CLIC3 updown 0.0019 0.0021 0.3201 -0.2703 11728036_a_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.0001 0.6594 ILMN_1775373 CMTM5 up 0.0238 0.2672 11753465_a_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.0005 0.4611 11728037_x_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.0012 0.5143 11753119_x_at CMTM5 CKLF-like MARVEL transmembrane domain containing 5 Extracellular Space cytokine up 0.0075 0.3004 11755746_s_at CNIH4 cornichon homolog 4 (Drosophila) Plasma Membrane other down 0.0007 -0.6023 ILMN_1714759 CNIH4 updown 0.0444 0.0143 0.2671 -0.205 11723416_x_at CNN2 calponin 2 Cytoplasm other down 0 -0.3932 ILMN_1770290 CNN2 updown 0.0312 0.0464 0.3136 -0.2335 11748403_x_at CNN2 calponin 2 Cytoplasm other down 0.0011 -0.5452 11723414_a_at CNN2 calponin 2 Cytoplasm other down 0.0015 -0.4703 11723415_s_at CNN2 calponin 2 Cytoplasm other down 0.0024 -0.4695 11734956_a_at CNTNAP2 contactin associated protein-like 2 Plasma Membrane other down 0 -0.6362 ILMN_1690223 CNTNAP2 down 0 -0.6385 11741710_a_at COL6A3 collagen, type VI, alpha 3 Extracellular Space other collagenase clostridiumup histolyticum 0.0078 0.4866 ILMN_1706643 COL6A3 up 0.0386 0.1916 11753841_x_at COMMD6 COMM domain containing 6 unknown other updown 0 0 0.5099 -0.8318 ILMN_1777378 COMMD6 updown 0.0383 0.0098 -0.0059 -0.2189 11733495_a_at COMMD6 COMM domain containing 6 unknown other updown 0 0 0.3918 -0.8735 11733496_x_at COMMD6 COMM domain containing 6 unknown other updown 0 0 0.3502 -0.6778 11756875_x_at COMMD6 COMM domain containing 6 unknown other updown 0 0.0004 0.4726 -0.8582 11733497_a_at COMMD6 COMM domain containing 6 unknown other up 0.011 0.5019 11720069_s_at COMMD8 COMM domain containing 8 unknown other up 0.0243 0.3378 ILMN_1765644 COMMD8 up 0.0152 0.1672 11732141_a_at COX16 COX16 cytochrome c oxidase assembly homolog (S. cerevisiae) Cytoplasm other down 0.0156 -0.5512 ILMN_1706305 COX16 down 0.0018 -0.2878 11715349_a_at COX7C cytochrome c oxidase subunit VIIc Cytoplasm enzyme down 0.0009 -0.6457 ILMN_1798189 COX7C updown 0 0 0.2855 -0.6146 11735847_a_at CPA5 carboxypeptidase A5 Extracellular Space peptidase up 0.0001 0.339 ILMN_1791530 CPA5 up 0 0.3165 11727130_a_at CPD carboxypeptidase D Extracellular Space peptidase up 0.0248 0.6811 ILMN_1703074 CPD up 0.0356 0.1944 11724951_s_at CPEB2 cytoplasmic polyadenylation element binding protein 2 Cytoplasm other down 0.0128 -0.6135 ILMN_1774948 CPEB2 down 0.0088 -0.2355 11726485_at CPED1 cadherin-like and PC-esterase domain containing 1 Cytoplasm other down 0 -0.798 ILMN_1677038 CPED1 down 0.0418 -0.1752 11721433_a_at CRBN cereblon Cytoplasm enzyme down 0.0144 -0.5789 ILMN_1668582 CRBN down 0.006 -0.2814 11762865_a_at CREB5 cAMP responsive element binding protein 5 Nucleus transcription regulator up 0.0208 0.6378 ILMN_1731714 CREB5 updown 0.0009 0.0013 0.2796 -0.2568 11739552_a_at CREB5 cAMP responsive element binding protein 5 Nucleus transcription regulator down 0.0043 -0.5499 11750879_a_at CREB5 cAMP responsive element binding protein 5 Nucleus transcription regulator down 0.0154 -0.3367 11729632_a_at CSDA cold shock domain protein A Nucleus transcription regulator up 0.0442 0.4961 ILMN_1782788 CSDA updown 0 0.001 0.4742 -0.1046 11729633_x_at CSDA cold shock domain protein A Nucleus transcription regulator up 0.0488 0.5513 11725124_at CST7 cystatin F (leukocystatin) Extracellular Space other down 0.0085 -0.5552 ILMN_1679826 CST7 updown 0 0 0.1455 -0.5297 11757500_a_at CTDSPL CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase-likeNucleus other updown 0 0.0112 0.6328 -0.1556 ILMN_1683444 CTDSPL updown 0 0.0444 0.3583 -0.0121 11725332_a_at CTSL1 cathepsin L1 Cytoplasm peptidase up 0.0396 0.5343 ILMN_1812995 CTSL1 up 0.0149 0.3098 CTSL1 20926012 CTSL1 enhances angiogenesis by increasing extracellular matrix degradation and remodelling. 11746740_a_at CTTN cortactin Plasma Membrane other updown 0 0.0009 0.5352 -0.4966 ILMN_1744912 CTTN updown 0 0.0378 0.3857 -0.0937 11748448_a_at CTTN cortactin Plasma Membrane other updown 0 0.0013 0.3552 -0.5765 11719366_s_at CXCL1 chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)Extracellular Space cytokine down 0.0198 -0.4992 ILMN_1787897 CXCL1 down 0.0415 -0.1832 11754114_a_at CXCL1 chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)Extracellular Space cytokine down 0.0243 -0.4197 21518789 CXCL10 concentration in blood increases during neonatal polymicrobial sepsis, and the blockade of CXCL10 not only worsens recruitment and phagocytic function of macrophages, but also the survival of neonatal mice. (Demonstrated in murine model) 11720298_at CXCL10 chemokine (C-X-C motif) ligand 10 Extracellular Space cytokine MDX-1100 up 0.0002 0.5551 ILMN_1791759 CXCL10 up 0.0477 0.1459 CXCL10 21124994 CXCL10 exert direct antimicrobial effects in vitro against Bacillus anthracis spore and bacilli in a receptor-independent manner and contributes to pulmonary innate immunity. (Demonstrated in murine model) 11730972_x_at CYP4F12 cytochrome P450, family 4, subfamily F, polypeptide 12 Cytoplasm enzyme up 0.0194 0.4514 ILMN_1809384 CYP4F12 up 0.0027 0.392 11730971_a_at CYP4F12 cytochrome P450, family 4, subfamily F, polypeptide 12 Cytoplasm enzyme up 0.0233 0.5536 11749605_x_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.0019 -0.2417 ILMN_1736190 CYP4F3 updown 0.0122 0.0383 0.2114 -0.1678 11749604_s_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.0137 -0.4088 11749758_s_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.0192 -0.3054 11733297_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.0224 -0.2121 11716580_s_at CYSTM1 cysteine-rich transmembrane module containing 1 unknown other down 0.0003 -0.5424 ILMN_1761566 CYSTM1 updown 0.0008 0 0.1433 -0.5927 11716579_a_at CYSTM1 cysteine-rich transmembrane module containing 1 unknown other down 0.0005 -0.532 11724178_a_at DAAM2 dishevelled associated activator of morphogenesis 2 unknown other up 0 0.5898 ILMN_1752668 DAAM2 up 0.0401 0.2438 11743002_at DCTN6 dynactin 6 Cytoplasm enzyme down 0.0429 -0.6078 ILMN_1744059 DCTN6 down 0.0272 -0.1684 11721438_s_at DEFA1 (includes others) defensin, alpha 1 Cytoplasm other updown 0.0009 0 0.2546 -0.6363 ILMN_1725661 DEFA1 (includes others) updown 0 0 0.2836 -0.8338 ILMN_1679357 DEFA1 (includes others) updown 0 0 0.1369 -1.0857 Page 93 of 111 Diabetes

ILMN_1693262 DEFA1 (includes others) up 0.0276 0.1063 11732546_at DEFA4 defensin, alpha 4, corticostatin Extracellular Space other down 0 -0.3628 ILMN_1753347 DEFA4 down 0.0003 -0.2813 DEFA4 19024344 DEFA4 along with DEFA1 and DEFA3 are cationic alpha-defensin peptides that have multiple functions in the immune system. 11719707_a_at DHRS13 dehydrogenase/reductase (SDR family) member 13 unknown enzyme down 0.0401 -0.509 ILMN_1790781 DHRS13 down 0.0031 -0.3303 11723899_a_at DHRS9 dehydrogenase/reductase (SDR family) member 9 Cytoplasm enzyme down 0.014 -0.4809 ILMN_1733998 DHRS9 updown 0.0074 0 0.2476 -0.4269 11728731_s_at DSCC1 defective in sister chromatid cohesion 1 homolog (S. cerevisiae) Nucleus other down 0.0013 -0.6419 ILMN_1776577 DSCC1 down 0.0087 -0.2214 11719373_at DYNLT3 dynein, light chain, Tctex-type 3 Cytoplasm other down 0.0105 -0.6117 ILMN_1681890 DYNLT3 down 0.001 -0.3372 11747936_a_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other updown 0.04 0.0267 0.3433 -0.2839 ILMN_1810420 DYSF updown 0 0.005 0.5974 -0.2651 11745836_x_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other down 0.0105 -0.3042 11719223_a_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other down 0.0398 -0.2431 12954221 EIF2AK2 is a protein kinase that is regulated by RNA and is an important mediator of the antiviral and anti proliferative actions of interferon (IFN). 11737718_a_at EEF1E1 eukaryotic translation elongation factor 1 epsilon 1 Cytoplasm translation regulator down 0.0022 -0.6166 ILMN_1725105 EEF1E1 down 0.0304 -0.2091 12954221 EIF2AK2 binds both SP1 and SP3 but only SP3 functions as part of the interferon-inducible complex with ISGF-3 proteins, consisting of STAT1, STAT2, and IRF9. 11743582_a_at EEF1E1 eukaryotic translation elongation factor 1 epsilon 1 Cytoplasm translation regulator down 0.0198 -0.4906 19028691 EIF2AK2 enhances the induction of interferon-beta and apoptosis mediated by cytoplasmic RNA sensors where in addition to MAVS and IRF3 but not TRIF, it is required for maximal type I IFN-beta induction and the induction of apoptosis by both transfected T7 11730991_a_at EIF2AK2 eukaryotic translation initiation factor 2-alpha kinase 2 Cytoplasm kinase updown 0.0055 0.0043 0.3479 -0.4463 ILMN_1706502 EIF2AK2 updown 0 0.0008 0.2891 -0.3417 EIF2AK2 20485506 EIF2AK2 is used by hepatitis C virus to restrain its ability to induce IFN through the RIG-I/MAVS pathway. 11731775_a_at EMR1 egf-like module containing, mucin-like, hormone receptor-like 1 Plasma Membrane G-protein coupled receptor up 0.0051 0.5585 ILMN_1780601 EMR1 up 0.0051 0.1198 23372823 EIF2AK2 binds to dsRNA to inhibit IFN induction triggered by dengue virus. 11748205_a_at EMR1 egf-like module containing, mucin-like, hormone receptor-like 1 Plasma Membrane G-protein coupled receptor up 0.0175 0.5227 22912779 Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse) 11735193_x_at EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 Plasma Membrane G-protein coupled receptor down 0.0192 -0.54 ILMN_1800524 EMR2 updown 0.0014 0.0273 0.3437 -0.3616 23115300 Herpes simplex virus evades antiviral host defence by interacting with EIF2AK2 (PKR) to inhibit autophagy. 11735192_a_at EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 Plasma Membrane G-protein coupled receptor down 0.0208 -0.4262 23236554 Bacterial dsRNA or poly(I:C) induces tyrosine phosphorylation of PKR activation by JAK kinases. 11752837_x_at EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 Plasma Membrane G-protein coupled receptor down 0.0359 -0.3735 11729574_at ENC1 ectodermal-neural cortex 1 (with BTB-like domain) Nucleus peptidase down 0.0092 -0.2786 ILMN_1779147 ENC1 down 0.0233 -0.1913 11725009_a_at EPB42 erythrocyte membrane protein band 4.2 Plasma Membrane transporter updown 0 0.0003 0.9036 -0.4661 ILMN_1814397 EPB42 updown 0.0003 0.006 0.249 -0.1773 11741343_a_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0 0.8552 ILMN_1671686 EPB49 up 0 0.3162 11747661_x_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0 0.7753 11724319_x_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0 0.9467 11741344_x_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0 0.8124 11747660_a_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0 0.8344 11726219_x_at EPB49 erythrocyte membrane protein band 4.9 (dematin) Plasma Membrane other up 0 0.8624 11731181_a_at EPSTI1 epithelial stromal interaction 1 (breast) unknown other down 0.0006 -0.2359 ILMN_1688566 EPSTI1 updown 0.001 0.0002 0.1648 -0.0478 11722573_a_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase down 0.005 -0.2923 ILMN_1743145 ERAP2 down 0.0007 -0.1367 11731787_x_at ERC1 ELKS/RAB6-interacting/CAST family member 1 Cytoplasm other down 0 -0.4811 ILMN_1660547 ERC1 down 0.0041 -0.2147 11754048_a_at ERH enhancer of rudimentary homolog (Drosophila) Nucleus other down 0.0199 -0.471 ILMN_1781795 ERH down 0.0002 -0.3679 11745025_a_at ERLIN2 ER lipid raft associated 2 Plasma Membrane other down 0.041 -0.477 ILMN_1700549 ERLIN2 down 0.0106 -0.2932 11726321_a_at ERO1L ERO1-like (S. cerevisiae) Cytoplasm enzyme down 0.0083 -0.4803 ILMN_1744963 ERO1L updown 0.0202 0.0318 0.2345 -0.323 11733841_a_at EVI2A ecotropic viral integration site 2A Plasma Membrane transmembrane receptor down 0 -0.7005 ILMN_1733579 EVI2A updown 0.0001 0 0.3213 -0.6739 11752423_a_at F13A1 coagulation factor XIII, A1 polypeptide Extracellular Space enzyme up 0.0008 0.7102 ILMN_1717163 F13A1 up 0.0001 0.3093 11716479_s_at F13A1 coagulation factor XIII, A1 polypeptide Extracellular Space enzyme up 0.017 0.5157 11720023_a_at FAM118A family with sequence similarity 118, member A unknown other up 0.0028 -0.074 ILMN_1809147 FAM118A up 0.0038 0.1612 11746669_a_at FAM118A family with sequence similarity 118, member A unknown other up 0.0051 -0.031 11755895_a_at FAM129A family with sequence similarity 129, member A Cytoplasm other up 0.0059 0.5172 ILMN_1810725 FAM129A updown 0 0.0066 0.4356 -0.1751 11739154_at FAM129A family with sequence similarity 129, member A Cytoplasm other up 0.0069 0.2339 ILMN_1667966 FAM129A up 0 0.3369 11740946_at FAM153B family with sequence similarity 153, member B unknown other up 0.0381 0.4122 ILMN_1798557 FAM153B up 0.0131 0.1431 11739340_at FAM46C family with sequence similarity 46, member C Extracellular Space other down 0.032 -0.2996 ILMN_1713266 FAM46C down 0.0204 -0.2662 11719151_at FAM83H family with sequence similarity 83, member H unknown other up 0.0388 0.5581 ILMN_1751328 FAM83H up 0.0005 0.2969 11756362_x_at FCGR1B Fc fragment of IgG, high affinity Ib, receptor (CD64) Plasma Membrane transmembrane receptor up 0.018 0.3824 ILMN_1760133 FCGR1B up 0.0326 0.2348 11724171_a_at FCHO2 FCH domain only 2 Cytoplasm other down 0.0001 -0.7488 ILMN_1670322 FCHO2 down 0.0044 -0.3046 11724172_s_at FCHO2 FCH domain only 2 Cytoplasm other down 0.0143 -0.5659 11750086_s_at FGFBP2 fibroblast growth factor binding protein 2 Extracellular Space other updown 0.0257 0.0076 0.3745 -0.4308 ILMN_1761945 FGFBP2 updown 0 0 0.3142 -0.423 11722782_at FGFBP2 fibroblast growth factor binding protein 2 Extracellular Space other down 0.0027 -0.4893 11763278_s_at FGFR1OP2 FGFR1 oncogene partner 2 Cytoplasm other down 0.0107 -0.5794 ILMN_1657436 FGFR1OP2 down 0.0205 -0.2471 11736116_a_at FGFR1OP2 FGFR1 oncogene partner 2 Cytoplasm other down 0.0135 -0.6063 11743133_a_at FKBP8 FK506 binding protein 8, 38kDa Cytoplasm other up 0.0084 0.5451 ILMN_1733947 FKBP8 updown 0.0021 0.0436 0.3033 -0.1617 11743134_x_at FKBP8 FK506 binding protein 8, 38kDa Cytoplasm other up 0.0221 0.5427 11746216_x_at FKBP8 FK506 binding protein 8, 38kDa Cytoplasm other up 0.0237 0.5058 11744140_a_at FOLR3 folate receptor 3 (gamma) Extracellular Space other updown 0.0351 0 -0.4578 -0.9694 ILMN_1730454 FOLR3 updown 0.0066 0 -0.2285 -0.5684 11744141_x_at FOLR3 folate receptor 3 (gamma) Extracellular Space other down 0 -1.3103 11745309_a_at FRMD3 FERM domain containing 3 unknown other up 0.007 0.2872 ILMN_1698725 FRMD3 updown 0 0.0059 0.5252 -0.3004 11750746_a_at FRMD3 FERM domain containing 3 unknown other up 0.0086 0.5836 11736092_at GCA grancalcin, EF-hand calcium binding protein Cytoplasm other down 0.0004 -0.6318 ILMN_1800602 GCA down 0.0019 -0.3573 11728937_at GFRA2 GDNF family receptor alpha 2 Plasma Membrane transmembrane receptor up 0.015 0.6241 ILMN_1656300 GFRA2 up 0.0426 0.2091 11732432_a_at GK glycerol kinase Cytoplasm kinase down 0.0015 -0.6163 ILMN_1725471 GK updown 0.0036 0.0091 0.225 -0.2692 11734201_s_at GK glycerol kinase Cytoplasm kinase down 0.0087 -0.3921 11750720_s_at GK glycerol kinase Cytoplasm kinase down 0.0127 -0.5581 11718048_a_at GLRX glutaredoxin (thioltransferase) Cytoplasm enzyme down 0.0006 -0.6339 ILMN_1737308 GLRX down 0.0015 -0.3524 GLRX 21078302 GLRX (GRX-1), a degluationylation enzyme, activates TRAF6 and is responsible for IL1R / TLR-dependent induction of NFkB pathway. 11747441_a_at GLRX glutaredoxin (thioltransferase) Cytoplasm enzyme down 0.0013 -0.5939 11749165_a_at GLT1D1 glycosyltransferase 1 domain containing 1 Extracellular Space enzyme down 0.0473 -0.4284 ILMN_1656327 GLT1D1 updown 0.0029 0.0028 0.2384 -0.2856 11724167_s_at GLT25D2 glycosyltransferase 25 domain containing 2 unknown other down 0.0102 -0.4265 ILMN_1736742 GLT25D2 updown 0.001 0.0083 -0.0374 -0.1224 11724166_a_at GLT25D2 glycosyltransferase 25 domain containing 2 unknown other down 0.0141 -0.4713 11720202_at GMPR guanosine monophosphate reductase Cytoplasm enzyme up 0.0007 0.5537 ILMN_1729487 GMPR up 0.0006 0.3713 11723488_at GNAZ guanine nucleotide binding protein (G protein), alpha z polypeptide Plasma Membrane enzyme down 0.0048 -0.47 ILMN_1766182 GNAZ down 0.0002 -0.338 11749333_a_at GNL3 guanine nucleotide binding protein-like 3 (nucleolar) Nucleus other down 0.0066 -0.6402 ILMN_1806106 GNL3 down 0.0008 -0.3149 11763755_a_at GNLY granulysin Cytoplasm other down 0 -0.6889 ILMN_1708779 GNLY updown 0 0.0002 0.176 -0.2275 11756632_a_at GNLY granulysin Cytoplasm other down 0.0204 -0.5018 11763756_x_at GNLY granulysin Cytoplasm other down 0.0447 -0.4648 11761997_at GPR125 G protein-coupled receptor 125 Plasma Membrane G-protein coupled receptor down 0.0143 -0.3439 ILMN_1674181 GPR125 down 0.0014 -0.3484 11750979_a_at GPR97 G protein-coupled receptor 97 Plasma Membrane G-protein coupled receptor up 0.0307 0.4225 ILMN_1765941 GPR97 up 0.0377 0.2916 11718223_a_at GSPT1 G1 to S phase transition 1 Cytoplasm translation regulator up 0.0203 0.3968 ILMN_1750130 GSPT1 up 0 0.4531 11719246_a_at GSTT1 glutathione S-transferase theta 1 Cytoplasm enzyme up 0.0056 0.6507 ILMN_1730054 GSTT1 up 0.0402 0.1461 11745557_x_at GYPB glycophorin B (MNS blood group) Plasma Membrane other up 0.002 0.6414 ILMN_1683093 GYPB up 0.0001 0.3136 11753827_x_at GYPB glycophorin B (MNS blood group) Plasma Membrane other up 0.0025 0.4862 11745299_x_at GYPB glycophorin B (MNS blood group) Plasma Membrane other up 0.0033 0.5683 11753662_x_at GYPB glycophorin B (MNS blood group) Plasma Membrane other up 0.0033 0.5953 11755052_s_at GYPE glycophorin E (MNS blood group) Plasma Membrane other up 0.001 0.3077 ILMN_1695187 GYPE updown 0 0.0048 0.3948 0.0036 11720496_at GZMA granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3) Cytoplasm peptidase down 0.0405 -0.2348 ILMN_1779324 GZMA down 0 -0.2816 11728125_a_at GZMH granzyme H (cathepsin G-like 2, protein h-CCPX) Cytoplasm peptidase updown 0.0001 0.0147 0.3464 -0.2566 ILMN_1731233 GZMH updown 0 0 0.5656 -0.3475 11734159_a_at HACE1 HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 Cytoplasm enzyme down 0.0315 -0.3683 ILMN_1740217 HACE1 down 0.0024 -0.2599 11725438_a_at HBD hemoglobin, delta Cytoplasm transporter updown 0.0494 0.0147 0.3734 -0.2197 ILMN_1815527 HBD updown 0.0269 0.0199 0.1809 -0.1221 11725439_at HBD hemoglobin, delta Cytoplasm transporter updown 0.0007 0.021 0.3644 -0.1545 11735475_at HBQ1 hemoglobin, theta 1 unknown other up 0.0014 0.4813 ILMN_1696183 HBQ1 up 0.0002 0.35 11755386_a_at HDC histidine decarboxylase Cytoplasm enzyme updown 0.0139 0.0001 0.2386 -0.4831 ILMN_1792323 HDC updown 0 0 0.2948 -0.3247 11755374_a_at HERC5 HECT and RLD domain containing E3 ubiquitin protein ligase 5 Cytoplasm enzyme updown 0.0061 0 0.0675 -0.6201 ILMN_1729749 HERC5 updown 0 0.0014 0.2484 -0.3079 HERC5 20308324 HERC5 positively regulates the innate antiviral responses by sustaining IRF3 activation via a novel post-translational modification, ISGylation. 11718201_at HEY1 hairy/enhancer-of-split related with YRPW motif 1 Nucleus transcription regulator up 0.0017 0.4168 ILMN_1788203 HEY1 up 0.0327 0.205 11753759_x_at HINT1 histidine triad nucleotide binding protein 1 Nucleus enzyme down 0.0119 -0.5812 ILMN_1807710 HINT1 updown 0 0 0.3024 -0.6777 11719406_a_at HIPK2 homeodomain interacting protein kinase 2 Nucleus kinase up 0.0153 0.6246 ILMN_1889602 HIPK2 up 0.0004 0.2384 11719409_a_at HIPK2 homeodomain interacting protein kinase 2 Nucleus kinase up 0.0329 0.4972 11719407_a_at HIPK2 homeodomain interacting protein kinase 2 Nucleus kinase up 0.041 0.4639 11731694_s_at HIST1H2AB/HIST1H2AE histone cluster 1, H2ae Nucleus other up 0.0338 0.6084 ILMN_1756849 HIST1H2AB/HIST1H2AE up 0.0029 0.2526 11731693_at HIST1H2AB/HIST1H2AE histone cluster 1, H2ae Nucleus other up 0.0467 0.604 11724021_at HIST1H2BD histone cluster 1, H2bd Nucleus other down 0.0478 -0.4535 ILMN_1651496 HIST1H2BD down 0.0007 -0.2464 11728153_x_at HIST1H2BD histone cluster 1, H2bd Nucleus other down 0.0499 -0.2424 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other up 0 0.3534 ILMN_1671054 HLA-A updown 0.0088 0.0004 0.2972 -0.2591 11762119_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other up 0 0.4015 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other up 0.001 0.127 ILMN_1721113 HLA-C up 0 0.2053 11761071_at HLA-DOB major histocompatibility complex, class II, DO beta Plasma Membrane transmembrane receptor down 0.0364 -0.293 ILMN_1700428 HLA-DOB down 0.0002 -0.2984 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor up 0.0001 0.348 ILMN_1791534 HLA-DQA1 up 0.0482 0.1435 11745004_x_at HOPX HOP homeobox Nucleus transcription regulator down 0.0006 -0.5872 ILMN_1766643 HOPX down 0.0011 -0.2602 11749980_x_at HOPX HOP homeobox Nucleus transcription regulator down 0.0007 -0.6523 11727401_x_at HOPX HOP homeobox Nucleus transcription regulator down 0.0007 -0.5995 11734396_at HRASLS2 HRAS-like suppressor 2 unknown other down 0.0383 -0.3857 ILMN_1809259 HRASLS2 down 0.0165 -0.182 18950863 HSP90AA1 regulates the stability of transforming growth factor beta-activated kinase 1 (TAK1) in interleukin-1beta (IL1B)-induced cell signalling and IL1B-induced signalling by interacting with and maintaining the stability of TAK1, suggesting that HSP90A 11758308_s_at HSP90AA1 heat shock protein 90kDa alpha (cytosolic), class A member 1 Cytoplasm enzyme 17-dimethylaminoethylamino-17-demethoxygeldanamycin,down IPI-504,0.0346 cisplatin -0.425 ILMN_1691097 HSP90AA1 down 0.0012 -0.3127 HSP90AA1 17420470 HSP90AA1 (HSP90) positively regulates NOD1 activation. 11760254_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0379 0 0.2301 -0.7494 ILMN_1760062 IFI44 updown 0 0 0.3309 -0.3247 11748003_a_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0046 0 0.375 -0.609 15685448 IFI6 has a function as a cell survival protein by inhibiting mitochondrial-mediated apoptosis. 11760252_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0469 0 0.3457 -0.5271 20939681 IFI6 (G1P3) gene encodes a low molecular weight mitochondrial protein that stabilizes mitochondrial function and opposes apoptosis. 11719886_a_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0241 0 0.4095 -0.5021 16785313 IFIH1 (MDA5) recognizes distinct RNA viruses and plays a major role in the elimination of RNA viruses in vivo. 11760253_x_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0056 0.0007 0.3846 -0.1972 21637773 IFIH1 deficiency results in a delayed type I IFN and attenuated type III IFN response to rhinovirus infection, leading to a transient increase in viral titer. Upon recognition of viral dsRNA, IFIH1 synergizes with TLR3 to induce pro-inflammatory signals l 11746088_a_at IFI44 interferon-induced protein 44 Cytoplasm other down 0.0003 -0.3845 15563593 IFIH1 binds V proteins of paramyxoviruses and this inhibit its activation of the IFNB1 (IFN-beta) promoter. 11723234_at IFI44L interferon-induced protein 44-like unknown other updown 0.0003 0 0.3523 -0.4857 ILMN_1723912 IFI44L updown 0 0.0002 0.4559 -0.0937 23328395 Paramyxovirus V proteins bind to IFIH1 (MDA5) to disrupt viral RNA recognition and induction of antiviral immunity. 11723236_at IFI44L interferon-induced protein 44-like unknown other updown 0.0001 0 0.2779 -0.4163 20107606 IFIH1 is indispensable for sustained expression of IFN in response to paramyxovirus infection and provide the first evidence of MDA5-dependent containment of in vivo infections caused by (-) sense RNA viruses. 11723235_a_at IFI44L interferon-induced protein 44-like unknown other updown 0.0007 0 0.4541 -0.3501 19936053 IFIH1 (MDA5) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response. (Demonstrated in murine model) 11718986_a_at IFI6 interferon, alpha-inducible protein 6 Cytoplasm other down 0.0021 -0.4713 ILMN_1687384 IFI6 down 0.0051 -0.1725 IFI6 21245317 IFIH1 is an RNA helicase and is a key component in activating the expression of type I IFN in response to viral infection. Viral mRNA with 5' cap and 3' poly(A) from parainfluenza virus 5 is able to activate IFN expression through RNASEL-IFIH1 signalling 11761686_at IFIH1 interferon induced with helicase C domain 1 Nucleus enzyme down 0.0141 -0.5082 ILMN_1781373 IFIH1 down 0.0011 -0.2722 IFIH1 11805321 IFIH1 is a double-stranded RNA-dependent ATPase that contains both a caspase recruitment domain and RNA helicase motifs. IFIH1 may also function as a mediator of interferon (IFN)-induced growth inhibition and/or apoptosis. 11756820_a_at IFIT1 interferon-induced protein with tetratricopeptide repeats 1 Cytoplasm other updown 0.002 0 0.2552 -0.5168 ILMN_1707695 IFIT1 updown 0 0 0.2315 -0.3447 IFIT1 20386592 IFIT1 expression activates the IFN response during C. pneumoniae infection, mediated by intracellular nucleotide-sensing pattern recognition receptors (PRRs), which operate through a mechanism dependent on the bacterial type III secretion system (T3SS). 11721873_at IFIT2 interferon-induced protein with tetratricopeptide repeats 2 Cytoplasm other updown 0.0424 0 0.0793 -0.7491 ILMN_1739428 IFIT2 updown 0.0007 0.0002 0.1445 -0.4456 IFIT2 22745654 IFIT1 is an innate immune network bottleneck with the ability to suppress induction of TLR4 response genes in LPS-stimulated macrophages. (Demonstrated in mice) 11726656_a_at IFIT5 interferon-induced protein with tetratricopeptide repeats 5 unknown other down 0.0022 -0.4446 ILMN_1696654 IFIT5 down 0.0105 -0.3107 21642987 IFIT1 recognizes and directly binds to 5'-triphosphate RNA and functions as an innate inhibitor of viral replication and pathogenicity. (Demonstrated in murine model) 11726655_at IFIT5 interferon-induced protein with tetratricopeptide repeats 5 unknown other down 0.0063 -0.3215 22065572 IFIT2 expression imparts anti-viral immunity to restrict West Nile virus infection and control viral pathogenesis. (Demonstrated in mice) 11715239_x_at IFITM3 interferon induced transmembrane protein 3 Plasma Membrane other updown 0.0027 0 0.4391 -0.4883 ILMN_1805750 IFITM3 updown 0 0 0.1287 -0.6053 IFITM3 19108715 IFIT2 belongs to type 1 interferon response genes and is highly induced after stimulation with LPS and selectively affects LPS induced protein expression by regulation at different post-transcriptional levels. 11757763_s_at IGF2BP2 insulin-like growth factor 2 mRNA binding protein 2 Cytoplasm translation regulator updown 0.0014 0.038 0.5964 -0.3466 ILMN_1702447 IGF2BP2 updown 0 0.002 0.4457 -0.202 20601941 IFITM3 is post-translationally regulated by S-palmitoylation on membrane-proximal cysteines, which controls its clustering in membrane compartments and its antiviral activity against influenza virus. 11741712_a_at IGF2BP2 insulin-like growth factor 2 mRNA binding protein 2 Cytoplasm translation regulator up 0.0012 0.6281 20064371 IFITM3 is an antiviral restriction factor that mediates cellular resistance to influenza A H1N1 virus, West Nile virus, and Dengue virus. 11759852_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0 0 0.1044 -0.3589 ILMN_1908133 IGHG1 updown 0.0004 0.0005 0.1781 -0.3353 11760929_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0001 0 0.1099 -0.4379 11745244_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0002 0 0.0549 -0.7216 11760819_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0001 0 0.0728 -0.5768 11750231_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0001 0 0.0271 -0.6651 11754032_x_at IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) Extracellular Space other updown 0.0001 0 0.0548 -0.5138 22940097 IL15 secreted by inflammatory monocytes is critical for the differentiation of memory CD8(+) T and NK lymphocytes into antimicrobial effector cells. (Demonstrated in mice) 11725255_a_at IL15 interleukin 15 Extracellular Space cytokine down 0.0228 -0.581 ILMN_1724181 IL15 down 0.0467 -0.1795 IL15 22084435 IL15 regulates homeostasis and terminal maturation of NKT cells. (Demonstrated in mice) 11732017_a_at IL18RAP interleukin 18 receptor accessory protein Plasma Membrane transmembrane receptor down 0.003 -0.4966 ILMN_1721762 IL18RAP down 0.0003 -0.2442 20026737 IL15 is a pluripotent anti-apoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. IL15 prevents two immunopathologic hallmarks of sepsis, namel 11749598_a_at IL18RAP interleukin 18 receptor accessory protein Plasma Membrane transmembrane receptor down 0.0032 -0.592 22426547 IL1B is an inflammatory cytokine that binds to its primary receptor, IL1R1, that then recruits the accessory protein IL1RAP to form a signalling-competent heterotrimeric complex. 11719916_at IL1B interleukin 1, beta Extracellular Space cytokine IL-1 trap, canakinumabdown 0.015 -0.4967 ILMN_1775501 IL1B updown 0 0.0001 0.2786 -0.3047 IL1B 20620944 IL1B-producing conventional dendritic cells preserves and expands IL-22(+)AHR(+) immature human natural killer cells in the secondary lymphoid tissue. 11734541_a_at IL5RA interleukin 5 receptor, alpha Plasma Membrane transmembrane receptor up 0 0.8853 ILMN_1863116 IL5RA updown 0 0.0184 0.2518 -0.005 21170027 IL1B acts as a growth factor for neutrophil progenitors and as a survival factor for mature neutrophils. In the absence of IKBKB, the IL1B production is enhanced and provides a compensatory mechanism for maintaining antibacterial defense when NFKB is inhi 11753566_a_at IL5RA interleukin 5 receptor, alpha Plasma Membrane transmembrane receptor up 0 0.5803 21228274 IL1B secretion in macrophages is regulated by autophagy by two mechanisms; sequestering of pro-IL1B in autophagosome during TLR stimulation, and processing,secretion of IL1B in a NLRP3- and TRIF-dependent manner. 11728592_at IPO11 importin 11 Nucleus transporter down 0 -0.693 ILMN_1684746 IPO11 down 0.0077 -0.2785 22158745 IL1B is an important component of the cellular network involving macrophages and epithelial cells, which facilitates IL8 chemokine expression and aids neutrophil recruitment during pneumococcal pneumonia. 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator updown 0 0.0038 0.1737 -0.2112 ILMN_1670576 IRF5 updown 0 0.0004 0.177 -0.0159 IRF5 20195505 IL1B is an important proinflammatory cytokine that activates monocytes, macropages, and neutrophils. IL1B processing during infection is a complex process in which the inflammasomes are only one of several activation mechanisms. 11719292_a_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other down 0 -0.6195 ILMN_1665107 ITGB1BP1 down 0.0255 -0.2405 21602824 IL1B secretion is induced only during viable E. coli infection (as oppose to heat-killed E. coli or LPS); Viable bacteria specifically elicit cleavage of pro-IL1B. (Demonstrated in murine model) 11719293_s_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other down 0 -0.6065 21628463 IL1B secretion is tightly regulated by the redox status in myeloid cells. TLR engagement in monocytes induces ROS generation followed by a sustained antioxidant response and efficient IL1B secretion. In macrophages, the antioxidant systems are in an upreg 11732454_at KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 Plasma Membrane ion channel down 0 -0.7469 ILMN_1675756 KCNJ15 updown 0.0096 0 0.1035 -0.4818 21270399 IL1B derived from alveolar macrophages is the critical mediator which induces chemokine production in non-hematopoietic cells in the lung, resulting in swift and robust recruitment of infection-controlling neutrophils into the airways. (Demonstrated in mu 11732455_at KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 Plasma Membrane ion channel down 0.0016 -0.6062 20401526 Mature IL1B production requires, in addition to the synthesis of pro-IL1B, cleavage of the precursor protein by the inflammatory CASP1 (Caspase-1) which is controlled within the NLRP3 inflammasome. 11730465_at KCNJ2 potassium inwardly-rectifying channel, subfamily J, member 2 Plasma Membrane ion channel nicorandil, amiodaronedown 0.0089 -0.6018 ILMN_1780334 KCNJ2 down 0.0009 -0.38 18332133 IRF5 is activated by both TBK1 and MYD88 to form a homodimer that binds to and activates transcription of type I interferon and inflammatory cytokine genes. 11722627_at KIAA1033 KIAA1033 Cytoplasm other down 0.0147 -0.4075 ILMN_1782222 KIAA1033 down 0.0015 -0.3295 12600985 IRF5 can act as both an activator and a repressor of interferon (IFN) gene induction dependent on the IRF-interacting partner, and may be a part of the regulatory network that ensures timely expression of the immediate early inflammatory genes. 11720780_a_at KIAA1324 KIAA1324 Plasma Membrane other updown 0.0001 0.0065 0.4811 -0.3828 ILMN_1771482 KIAA1324 updown 0 0.0022 0.4597 -0.2747 22412986 Phosphorylation of IRF5 at ser451 and ser462 is the primary trigger of IRF5 function in nuclear accumulation, transcription and apoptosis. 11760258_x_at KIAA1324 KIAA1324 Plasma Membrane other up 0.0041 0.5552 11722881_at KIAA1468 KIAA1468 unknown other down 0.0215 -0.4971 ILMN_1798346 KIAA1468 down 0.0039 -0.3139 11742301_x_at KIR2DL3 (includes others) killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 3 Plasma Membrane other updown 0.002 0.0139 0.4563 -0.2446 ILMN_1667232 KIR2DL3 (includes others) updown 0.0477 0.0001 0.0995 -0.4015 11742216_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0 -0.5384 ILMN_1799134 KLRD1 updown 0.0005 0 0.0663 -0.5222 11753534_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0 -0.4993 11753535_x_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0009 -0.5026 11753484_x_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0015 -0.4923 11740451_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0015 -0.4951 11740452_x_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor down 0.0041 -0.5545 11723952_at KRT1 keratin 1 Cytoplasm other up 0 0.7521 ILMN_1735712 KRT1 up 0 0.6581 11740592_a_at KRT72 keratin 72 unknown other up 0.0071 0.3793 ILMN_1695812 KRT72 up 0 0.276 11753776_x_at LAIR2 leukocyte-associated immunoglobulin-like receptor 2 Plasma Membrane other down 0.0216 -0.5333 ILMN_1807491 LAIR2 down 0.0317 -0.1851 11733718_x_at LAIR2 leukocyte-associated immunoglobulin-like receptor 2 Plasma Membrane other down 0.0267 -0.3821 11749876_a_at LAMP2 lysosomal-associated membrane protein 2 Plasma Membrane enzyme down 0.001 -0.5535 ILMN_1673282 LAMP2 down 0.0342 -0.1699 11718769_a_at LAMTOR3 late endosomal/lysosomal adaptor, MAPK and MTOR activator 3 Cytoplasm other down 0.0318 -0.5066 ILMN_1659415 LAMTOR3 updown 0.0152 0.0015 0.2084 -0.3618 11718768_a_at LAMTOR3 late endosomal/lysosomal adaptor, MAPK and MTOR activator 3 Cytoplasm other down 0.0358 -0.562 11757634_a_at LCN2 lipocalin 2 Extracellular Space transporter updown 0.0001 0 0.3743 -0.5495 ILMN_1692223 LCN2 updown 0.0009 0 0.1463 -0.2849 11754408_s_at LDB2 LIM domain binding 2 Nucleus transcription regulator down 0 -0.4266 ILMN_1800697 LDB2 down 0.0193 -0.2427 11754409_x_at LDB2 LIM domain binding 2 Nucleus transcription regulator down 0.0142 -0.5455 11722353_s_at LDB2 LIM domain binding 2 Nucleus transcription regulator down 0.0262 -0.6003 11747931_a_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.0076 0.5802 ILMN_1904481 LEF1 up 0 0.5401 11746636_a_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.009 0.5382 ILMN_1679185 LEF1 up 0.0057 0.1974 11736566_a_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.0092 0.5114 11747932_x_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.0445 0.4635 11731798_a_at LGALS2 lectin, galactoside-binding, soluble, 2 Cytoplasm other down 0.0015 -0.4582 ILMN_1687306 LGALS2 down 0.0422 -0.1598 LGALS2 15356130 LGASL2 binds to T cells in a beta-galactoside-specific manner and acts as pro-apoptotic effector for activated T cells. 11752506_s_at LMNA lamin A/C Nucleus other up 0.004 0.5734 ILMN_1696749 LMNA up 0.0494 0.2503 11729750_a_at LPAR1 lysophosphatidic acid receptor 1 Plasma Membrane G-protein coupled receptor down 0.0276 -0.3811 ILMN_1701441 LPAR1 down 0.045 -0.2268 11743071_a_at LPAR6 lysophosphatidic acid receptor 6 Plasma Membrane G-protein coupled receptor updown 0.0427 0 0.2549 -0.4593 ILMN_1786429 LPAR6 updown 0 0 0.1879 -0.367 11725418_a_at LPCAT2 lysophosphatidylcholine acyltransferase 2 Cytoplasm enzyme up 0 0.6418 ILMN_1796335 LPCAT2 up 0 0.4174 LPCAT2 20663880 LPCAT2 is highly expressed in inflammatory cells and is activated by lipopolysaccharide (LPS) treatment through Toll-like receptor 4 (TLR4) and LPCAT2 phosphorylation through LPS-TLR4 signalling may directly depend on MAPK-activated protein kinase 2 (MAPK 11751459_x_at LRG1 leucine-rich alpha-2-glycoprotein 1 Extracellular Space other updown 0.0158 0.0203 0.4114 -0.293 ILMN_1805228 LRG1 updown 0.0033 0.0017 0.1853 -0.2694 Diabetes Page 94 of 111

11725368_at LRG1 leucine-rich alpha-2-glycoprotein 1 Extracellular Space other down 0.0062 -0.4365 11734144_s_at LRRC37A3 (includes others)leucine rich repeat containing 37, member A3 unknown other up 0.0467 0.3865 ILMN_1790114 LRRC37A3 (includes others)up 0.0466 0.2211 11732413_a_at LRRC8B leucine rich repeat containing 8 family, member B unknown other down 0.0063 -0.4835 ILMN_1838313 LRRC8B down 0.0192 -0.1691 19840871 LY96 (MD-2) recognizes only exogenous pathogen-associated molecular patterns (PAMPs) when complexed with TLR2-CD14 or TLR4-CD14. 11715419_at LY6E lymphocyte antigen 6 complex, locus E Plasma Membrane other up 0.0337 0.3696 ILMN_1695404 LY6E updown 0.0006 0.0002 0.0896 -0.3616 15852007 LY86 and CD180 interact directly with the TLR4 signalling complex, inhibiting its ability to bind microbial ligand. 11728507_at LY96 lymphocyte antigen 96 Plasma Membrane other updown 0 0 1.013 -0.6542 ILMN_1724533 LY96 updown 0 0 0.5829 -0.4178 LY96 10359581 LY96 is physically associated with TLR4 on the cell surface and confers responsiveness to lipopolysaccharide (LPS). 11715461_at LYZ lysozyme Extracellular Space enzyme down 0.027 -0.2518 ILMN_1815205 LYZ updown 0.0015 0 -0.0543 -0.4532 22433852 Amino acid Phe126 of LY96 acts as a hydrophobic switch driving agonist-dependent contacts necessary for TLR4 dimerization and activation. 11743772_a_at LZTFL1 leucine zipper transcription factor-like 1 unknown other down 0.0012 -0.756 ILMN_1815705 LZTFL1 down 0.005 -0.3237 22474354 Morphine binds to LY96, triggering TLR4 oligomerization and induces neuroinflammation within the central nervous system. 11724410_x_at MARCH2 membrane-associated ring finger (C3HC4) 2, E3 ubiquitin protein ligase Cytoplasm enzyme up 0.0433 0.4915 ILMN_1669592 MARCH2 up 0.0067 0.2839 ILMN_1703142 MARCH2 up 0.0105 0.2769 11723771_a_at MASTL microtubule associated serine/threonine kinase-like Cytoplasm kinase down 0.0341 -0.3542 ILMN_1682336 MASTL down 0.0303 -0.2086 21712422 TLR4::LY96 functions as intracellular LPS sensor and triggers a unique set of LPS responses upon recognition of phagocytosed bacteria in macrophages. (Demonstrated in murine model) 11743661_a_at MBNL1 muscleblind-like splicing regulator 1 Nucleus other down 0.0049 -0.4862 ILMN_1807304 MBNL1 down 0.0193 -0.2621 11763531_a_at METTL15 methyltransferase like 15 unknown other down 0.0049 -0.3923 ILMN_1738342 METTL15 down 0.0065 -0.261 11731270_a_at MGAM maltase-glucoamylase (alpha-glucosidase) Plasma Membrane enzyme miglitol, MDL 28574,down acarbose 0.0008 -0.3542 ILMN_1727177 MGAM down 0.0189 -0.2787 11731271_a_at MGAM maltase-glucoamylase (alpha-glucosidase) Plasma Membrane enzyme miglitol, MDL 28574,down acarbose 0.0092 -0.4119 11751744_a_at MMD monocyte to macrophage differentiation-associated Plasma Membrane other up 0 0.6141 ILMN_1733937 MMD up 0.0212 0.1655 11720022_a_at MME membrane metallo-endopeptidase Plasma Membrane peptidase down 0.0256 -0.4167 ILMN_1678170 MME updown 0 0.0032 0.3389 -0.196 11747693_a_at MME membrane metallo-endopeptidase Plasma Membrane peptidase down 0.0337 -0.4937 21873432 MMP9 and NEU1 cross-talk in alliance with TLR4 on the cell surface is a novel membrane sialidase-controlling mechanism that depends on ligand binding to its Toll-like receptor (TLR) to induce NEU1 activity, to influence receptor desialylation and subseque 11755860_a_at MME membrane metallo-endopeptidase Plasma Membrane peptidase down 0.0396 -0.5298 22496659 MMP9 inhibits influenza virus pathogenesis by mediating neutrophil migration to the respiratory tract. (Demonstrated in mice) 11719657_a_at MMP9 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)Extracellular Space peptidase down 0 -0.8217 ILMN_1796316 MMP9 updown 0.0108 0.0003 0.2257 -0.2913 MMP9 22860023 MMP9 cleaves the pulmonary collectin SFTPD (SP-D) leading to loss of its innate immune functions. (Demonstrated in mouse) 11740944_at MPL myeloproliferative leukemia virus oncogene Plasma Membrane transmembrane receptor eltrombopag, romiplostimup 0 0.3126 ILMN_1776640 MPL updown 0.0081 0.0165 0.1357 -0.2875 11715771_a_at MRPL13 mitochondrial ribosomal protein L13 Cytoplasm other down 0.0001 -0.5252 ILMN_1671158 MRPL13 down 0.0008 -0.3268 11715772_x_at MRPL13 mitochondrial ribosomal protein L13 Cytoplasm other down 0.0003 -0.5389 11745391_x_at MRPL3 mitochondrial ribosomal protein L3 Cytoplasm other down 0.019 -0.6087 ILMN_1713143 MRPL3 down 0.0002 -0.2548 11757551_a_at MRPL3 mitochondrial ribosomal protein L3 Cytoplasm other down 0.0437 -0.4071 11754705_a_at MRPL43 mitochondrial ribosomal protein L43 Cytoplasm translation regulator down 0.0202 -0.2599 ILMN_1652147 MRPL43 down 0.0389 -0.1593 ILMN_1700477 MRPL43 down 0.045 -0.2595 21460221 MSR1 deficiency leads to greater sensitivity to LPS-induced endotoxic shock. MSR1 down-regulates inflammatory gene expression in dendritic cells by suppressing TLR4-mediated activation of NFKB. 11721262_at MRPL50 mitochondrial ribosomal protein L50 Cytoplasm other down 0.0012 -0.711 ILMN_1664833 MRPL50 updown 0.0057 0 0.158 -0.4093 19914718 MSR1 is required for sensing human cytomegalovirus (HCMV) by endosomal TLR3 and TLR9 in monocytic THP-1 cells. 11756089_s_at MSR1 macrophage scavenger receptor 1 Plasma Membrane transmembrane receptor down 0 -0.5774 ILMN_1743301 MSR1 down 0.0007 -0.5145 MSR1 20162551 MRS1 (SR-A) is upregulated in TLR4-mediated LPS responses and these receptors contribute to the efficient capturing and clearance of invading microbial pathogens. 11737428_a_at MSR1 macrophage scavenger receptor 1 Plasma Membrane transmembrane receptor down 0.0002 -0.7141 21756882 MSR1, one of the principal receptors expressed on macrophages, suppresses macrophage activation by inhibiting the binding of lipopolysaccharide (LPS) to TLR4 in a competitive manner; thus playing a pivotal role in the regulation of the LPS-induced inflamm 11737429_x_at MSR1 macrophage scavenger receptor 1 Plasma Membrane transmembrane receptor down 0.004 -0.5333 22751446 Deletion of MSR1 results in protection from septic shock and modulation of TLR4 signalling in peritoneal macrophages. (Demonstrated in mice) 11744002_s_at MTHFD2 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolateCytoplasm cyclohydrolaseenzyme down 0.0405 -0.4382 ILMN_1674706 MTHFD2 updown 0.0048 0.006 0.2974 -0.2132 18062906 MX1 is an interferon-induced member of the dynamin superfamily of large GTPases, which inhibit a wide range of viruses by blocking an early stage of the replication cycle. 11716167_a_at MX1 myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse)Nucleus enzyme updown 0.0448 0.0003 0.2281 -0.5037 ILMN_1662358 MX1 updown 0.0016 0 0.1689 -0.4819 MX1 22531919 MX1 expression is upregulated by alpha-defensins in gigival epithelial cell. 11720703_at MYL4 myosin, light chain 4, alkali; atrial, embryonic Cytoplasm other up 0.005 0.511 ILMN_1684255 MYL4 up 0.0006 0.3276 20538602 MX1 GTPase is a key mediator of cell-autonomous innate immunity against a broad range of viruses such as influenza and bunyaviruses. 11729192_a_at MYNN myoneurin Nucleus transcription regulator down 0 -0.5298 ILMN_1672287 MYNN down 0.0016 -0.3082 11729193_s_at MYNN myoneurin Nucleus transcription regulator down 0.0005 -0.8592 11749019_a_at MYNN myoneurin Nucleus transcription regulator down 0.0124 -0.5744 11725136_a_at MYOM2 myomesin (M-protein) 2, 165kDa Cytoplasm other updown 0 0.0049 0.7012 0.5332 ILMN_1716733 MYOM2 updown 0 0.0003 0.7344 0.4174 11739475_s_at NAB1 NGFI-A binding protein 1 (EGR1 binding protein 1) Nucleus transcription regulator down 0.0242 -0.5341 ILMN_1774617 NAB1 updown 0.0335 0.0126 0.2935 -0.2511 18280719 NAIP is important for CASP1 activation and IL-1 processing. 11736898_s_at NAIP NLR family, apoptosis inhibitory protein unknown other down 0.012 -0.5589 ILMN_1788237 NAIP down 0.0009 -0.4087 NAIP 21918512 NAIP specifically recognizes the Chromobacterium violaceum type III secretion system protein, Cprl, and activates the NLRC4 inflammasome in macrophages. 11736899_x_at NAIP NLR family, apoptosis inhibitory protein unknown other down 0.0269 -0.4468 11760312_at NAMPT nicotinamide phosphoribosyltransferase Extracellular Space cytokine updown 0.0025 0.0113 0.5652 -0.4178 ILMN_1753111 NAMPT updown 0 0.0013 0.4915 -0.1626 NAMPT 22377803 NAMPT secretion is enhanced by extracellular ATP in LPS-primed monocytes. 11743110_at NAMPT nicotinamide phosphoribosyltransferase Extracellular Space cytokine down 0.006 -0.5435 ILMN_1653871 NAMPT updown 0.0003 0.0004 0.2405 -0.3501 11715369_s_at NDUFA4 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDa Cytoplasm enzyme down 0.0007 -0.6729 ILMN_1751258 NDUFA4 updown 0.0121 0 0.0709 -0.4505 11758717_x_at NDUFA4 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDa Cytoplasm enzyme down 0.0062 -0.4957 11749795_a_at NFIX nuclear factor I/X (CCAAT-binding transcription factor) Nucleus transcription regulator up 0 0.7482 ILMN_1694325 NFIX up 0.0214 0.3604 11750285_a_at NFIX nuclear factor I/X (CCAAT-binding transcription factor) Nucleus transcription regulator up 0.0078 0.4597 11750902_x_at NFIX nuclear factor I/X (CCAAT-binding transcription factor) Nucleus transcription regulator up 0.0344 0.4285 11725210_s_at NFXL1 nuclear transcription factor, X-box binding-like 1 Nucleus transcription regulator up 0.0016 0.418 ILMN_1682197 NFXL1 up 0.0242 0.2566 11761655_at NPCDR1 nasopharyngeal carcinoma, down-regulated 1 unknown other up 0.0005 0.4314 ILMN_1780774 NPCDR1 up 0.0248 0.1593 11748257_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other updown 0 0.0066 0.809 -0.1516 ILMN_1733581 NPRL3 updown 0 0.0003 0.6268 -0.2105 11724497_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other updown 0 0.0117 0.7145 -0.0119 11763176_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other updown 0 0.0238 0.7292 -0.2202 11753912_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other updown 0 0.0373 0.7052 -0.1823 11724496_a_at NPRL3 nitrogen permease regulator-like 3 (S. cerevisiae) unknown other up 0.0056 0.547 11718787_at NRGN neurogranin (protein kinase C substrate, RC3) Cytoplasm other updown 0 0.0338 0.7904 -0.1107 ILMN_1705686 NRGN updown 0 0.0107 0.4974 -0.1233 11748198_a_at NSG1 neuron specific gene family member 1 Cytoplasm other down 0.0114 -0.2023 ILMN_1772627 NSG1 down 0.001 -0.2302 11743423_a_at NSG1 neuron specific gene family member 1 Cytoplasm other down 0.0149 -0.2669 11727032_a_at NSG1 neuron specific gene family member 1 Cytoplasm other down 0.0216 -0.2919 11721042_at NSMCE2 non-SMC element 2, MMS21 homolog (S. cerevisiae) Nucleus enzyme down 0.0139 -0.4751 ILMN_1693210 NSMCE2 down 0.0226 -0.268 23319625 OAS1 is a cytoplasmic dsRNA sensor. 11724255_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme down 0 -0.6336 ILMN_1675640 OAS1 updown 0.0121 0.0002 0.0399 -0.4026 OAS1 21190483 OAS1 is a pathogen recognition receptor for the viral pathogen-associated molecular pattern, double-stranded RNA. Upon recognition of dsRNA, the OAS1 activates RNASEL to cleave ssRNA. The OAS/RNASEL pathway triggers the RIG-I pathway and induce IFNB produ 11740891_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme down 0.0015 -0.4653 ILMN_1658247 OAS1 updown 0 0.0003 0.2954 -0.1036 11719588_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme down 0.0043 -0.5648 11724256_s_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme down 0.0338 -0.4745 11723698_a_at OAS3 2-5-oligoadenylate synthetase 3, 100kDa Cytoplasm enzyme updown 0.0105 0 0.1827 -0.7737 ILMN_1745397 OAS3 updown 0 0 0.3341 -0.3335 OAS3 21190483 OAS3 is a pathogen recognition receptor for the viral pathogen-associated molecular pattern, double-stranded RNA. Upon recognition of dsRNA, the OAS3 activates RNASEL to cleave ssRNA. The OAS/RNASEL pathway triggers the RIG-I pathway and induce IFNB produ 11723699_s_at OAS3 2-5-oligoadenylate synthetase 3, 100kDa Cytoplasm enzyme updown 0.0422 0 0.2364 -0.781 11726364_x_at OASL 2-5-oligoadenylate synthetase-like Cytoplasm enzyme up 0.0006 0.2938 ILMN_1674811 OASL up 0.0028 0.1385 11744920_a_at ODF3B outer dense fiber of sperm tails 3B unknown enzyme down 0.0488 -0.3023 ILMN_1738867 ODF3B down 0.0349 -0.253 11736090_a_at OLIG2 oligodendrocyte lineage transcription factor 2 Nucleus transcription regulator updown 0 0.0008 1.1575 -0.2214 ILMN_1727567 OLIG2 updown 0 0 0.4594 -0.1467 11744904_a_at ORM1 orosomucoid 1 Extracellular Space other up 0 0.9185 ILMN_1696584 ORM1 up 0 0.4896 11744905_x_at ORM1 orosomucoid 1 Extracellular Space other up 0 0.8757 11754065_x_at ORM1 orosomucoid 1 Extracellular Space other up 0 0.8929 11758794_x_at ORM1 orosomucoid 1 Extracellular Space other up 0 0.9245 11723341_x_at OXR1 oxidation resistance 1 Cytoplasm other down 0.0294 -0.5285 ILMN_1737462 OXR1 updown 0.0242 0 0.0816 -0.5662 11752300_a_at PADI2 peptidyl arginine deiminase, type II Cytoplasm enzyme down 0.0001 -0.7329 ILMN_1771223 PADI2 down 0 -0.375 11727597_at PADI2 peptidyl arginine deiminase, type II Cytoplasm enzyme down 0.0157 -0.1714 11745141_a_at PADI2 peptidyl arginine deiminase, type II Cytoplasm enzyme down 0.0191 -0.4317 11728043_at PANX2 pannexin 2 Plasma Membrane transporter up 0.0474 0.4271 ILMN_1694810 PANX2 up 0.0405 0.2278 11749412_a_at PARP14 poly (ADP-ribose) polymerase family, member 14 Cytoplasm other up 0.0239 0.4434 ILMN_1691731 PARP14 up 0.028 0.1779 11754379_at PARP9 poly (ADP-ribose) polymerase family, member 9 Nucleus other up 0.0167 0.4619 ILMN_1731224 PARP9 updown 0.0481 0.0059 0.1352 -0.2375 11719414_a_at PBX1 pre-B-cell leukemia homeobox 1 Nucleus transcription regulator up 0 0.7444 ILMN_1784678 PBX1 up 0.0119 0.2875 11757871_s_at PBX1 pre-B-cell leukemia homeobox 1 Nucleus transcription regulator up 0 0.5814 11749792_a_at PBX1 pre-B-cell leukemia homeobox 1 Nucleus transcription regulator up 0.0025 0.4348 11758070_s_at PBX1 pre-B-cell leukemia homeobox 1 Nucleus transcription regulator up 0.0118 0.4594 11723385_s_at PCSK6 proprotein convertase subtilisin/kexin type 6 Extracellular Space peptidase down 0.0104 -0.4886 ILMN_1802550 PCSK6 down 0.0144 -0.2102 19734906 PELI1 is a ubiquitin ligase that facilitates TRIF-dependent Toll-like receptor signalling and pro-inflammatory cytokine production. 11716974_a_at PDK4 pyruvate dehydrogenase kinase, isozyme 4 Cytoplasm kinase up 0.0097 0.5232 ILMN_1684982 PDK4 up 0 0.3331 17997719 PELI1 (pellino) isoforms are E3 ubiquitin ligases that mediate the IL-1-stimulated formation of K63-pUb-IRAK1 in cells, contributing to the activation of IKBKB and NF-kappaB, as well as other signalling pathways dependent on IRAK1 and IRAK4. 11745912_a_at PELI1 pellino E3 ubiquitin protein ligase 1 Cytoplasm enzyme down 0.0074 -0.442 ILMN_1679268 PELI1 down 0.0057 -0.2881 PELI1 21120624 PELI1 is an adaptor protein involved in IL1R/TLR signaling. PELI1 is sumoylated by SUMO1at 5 lysine residues, and binds to the SUMO-conjugating enzyme UBE2I. 11756227_s_at PEX2 peroxisomal biogenesis factor 2 Cytoplasm other down 0.0171 -0.5309 ILMN_1743299 PEX2 down 0.0003 -0.2608 20171181 Discrete regions of PELI1 are bound by SMAD6 and SMAD7 via their MH2 domains to mediate TGF-beta1-induced negative regulation of IL-1R/TLR signalling. 11720549_a_at PEX6 peroxisomal biogenesis factor 6 Cytoplasm enzyme up 0.0443 0.3058 ILMN_1683279 PEX6 up 0.0074 0.208 11756898_a_at PGM5 phosphoglucomutase 5 Cytoplasm enzyme up 0.0009 0.4442 ILMN_1781388 PGM5 up 0.0029 0.1903 ILMN_1709590 PGM5 up 0.0167 0.2043 11733294_at PHF20L1 PHD finger protein 20-like 1 unknown other down 0.0404 -0.4648 ILMN_1732985 PHF20L1 down 0.0078 -0.2925 11720361_at PHIP pleckstrin homology domain interacting protein Nucleus other down 0.0178 -0.6108 ILMN_1898682 PHIP updown 0 0.0047 0.3983 -0.2837 11721650_at PI3 peptidase inhibitor 3, skin-derived Extracellular Space other down 0.0005 -0.5517 ILMN_1693192 PI3 updown 0.0013 0 0.2345 -0.5759 11725842_a_at PIF1 PIF1 5-to-3 DNA helicase homolog (S. cerevisiae) Nucleus enzyme down 0.0061 -0.2139 ILMN_1737699 PIF1 down 0.0487 -0.1606 11725271_a_at PIGA phosphatidylinositol glycan anchor biosynthesis, class A Cytoplasm enzyme down 0.0377 -0.4763 ILMN_1705985 PIGA down 0.0002 -0.3728 ILMN_1802390 PIGA down 0.0256 -0.3924 21779477 Pml(-/-) mice are resistant to LPS-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-kB pathway. Pml(-/-) mice also exhibit impaired functi 11728557_s_at PML promyelocytic leukemia Nucleus transcription regulator arsenic trioxide up 0.0318 0.5048 ILMN_1728019 PML up 0.037 0.1933 PML 21131187 PML, a member of the TRIM protein family, is upregulated by Type I and Type II interferons and have been found to restrict viral replication by modulating the RIG-I pathway. 11715585_a_at PMP22 peripheral myelin protein 22 Plasma Membrane other up 0 0.7891 ILMN_1785646 PMP22 updown 0 0.0118 0.4799 -0.1264 11729581_x_at PPDPF pancreatic progenitor cell differentiation and proliferation factor homolog (zebrafish)unknown other up 0.0488 0.3062 ILMN_1720430 PPDPF up 0.0123 0.2272 11730267_a_at PPIG peptidylprolyl isomerase G (cyclophilin G) Nucleus enzyme down 0.0119 -0.4649 ILMN_1807611 PPIG down 0.045 -0.2741 11722879_a_at PPP2R2B protein phosphatase 2, regulatory subunit B, beta Cytoplasm phosphatase up 0.0248 0.3149 ILMN_1660732 PPP2R2B updown 0.0001 0 0.3153 -0.4691 11747295_a_at PRF1 perforin 1 (pore forming protein) Cytoplasm other up 0.0264 0.4108 ILMN_1740633 PRF1 up 0.0131 0.207 11732808_a_at PROK2 prokineticin 2 Extracellular Space other updown 0.0216 0 0.0835 -0.8609 ILMN_1775257 PROK2 updown 0.0015 0 0.1659 -0.779 11732809_a_at PROK2 prokineticin 2 Extracellular Space other down 0 -0.6218 11720134_s_at PROS1 protein S (alpha) Extracellular Space other updown 0 0.0216 0.4951 -0.0717 ILMN_1671928 PROS1 updown 0 0.0327 0.2943 -0.2157 PROS1 22043818 PROS1 works with GAS6 to synergistically suppress the basal and TLR-triggered production of inflammatory cytokines in macrophages. (Demonstrated in mice) 11720133_a_at PROS1 protein S (alpha) Extracellular Space other up 0.0288 0.2841 11731941_at PRSS33 protease, serine, 33 Extracellular Space peptidase updown 0 0.0029 1.2598 -0.2633 ILMN_1736831 PRSS33 updown 0 0.0009 0.6564 -0.1822 11761869_at PSIP1 PC4 and SFRS1 interacting protein 1 Nucleus other up 0.0011 0.7052 ILMN_1788701 PSIP1 up 0.0027 0.383 11720983_s_at PSMC6 proteasome (prosome, macropain) 26S subunit, ATPase, 6 Nucleus peptidase down 0.003 -0.4588 ILMN_1655316 PSMC6 updown 0.0044 0.0063 0.3198 -0.2681 11735589_at PTGDR prostaglandin D2 receptor (DP) Plasma Membrane G-protein coupled receptor down 0.0138 -0.5016 ILMN_1706268 PTGDR down 0.0171 -0.2272 11728067_at PTGDR2 prostaglandin D2 receptor 2 Plasma Membrane G-protein coupled receptor up 0 0.7885 ILMN_1703326 PTGDR2 updown 0 0.0031 0.3952 -0.3384 11719827_a_at QPCT glutaminyl-peptide cyclotransferase Cytoplasm enzyme down 0.0287 -0.4338 ILMN_1741727 QPCT updown 0.0076 0 0.1671 -0.4824 11719828_x_at QPCT glutaminyl-peptide cyclotransferase Cytoplasm enzyme down 0.0294 -0.456 11740390_a_at RBM47 RNA binding motif protein 47 unknown other down 0.0101 -0.4371 ILMN_1689046 RBM47 down 0.0312 -0.251 11725237_a_at RBPMS2 RNA binding protein with multiple splicing 2 unknown other up 0 1.2686 ILMN_1808238 RBPMS2 up 0 0.7317 11729123_a_at RCN2 reticulocalbin 2, EF-hand calcium binding domain Cytoplasm other down 0.0177 -0.4417 ILMN_1662129 RCN2 down 0.0063 -0.2378 11729124_x_at RCN2 reticulocalbin 2, EF-hand calcium binding domain Cytoplasm other down 0.0192 -0.4188 11739588_a_at RERE arginine-glutamic acid dipeptide (RE) repeats Nucleus other up 0.0338 0.3932 ILMN_1802380 RERE up 0.0017 0.2686 11755743_a_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme updown 0.001 0 0.2035 -0.2249 ILMN_1730628 RNASE2 updown 0.0005 0 0.134 -0.2354 11729772_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme updown 0.0019 0 0.0483 -0.2066 11757329_s_at RPL26 ribosomal protein L26 Cytoplasm other updown 0.0003 0.0001 0.3808 -0.7015 ILMN_1731546 RPL26 updown 0 0 0.3768 -0.6172 11757027_x_at RPL31 ribosomal protein L31 Nucleus other updown 0.0209 0.0018 0.2721 -0.5083 ILMN_1754195 RPL31 updown 0 0 0.3811 -0.4839 11757421_x_at RPL31 ribosomal protein L31 Nucleus other updown 0.0199 0.0022 0.4621 -0.5472 11729386_s_at RPL31 ribosomal protein L31 Nucleus other up 0 0.6874 11729387_x_at RPL31 ribosomal protein L31 Nucleus other up 0.0003 0.4507 11746229_a_at RPL31 ribosomal protein L31 Nucleus other down 0.0016 -0.3694 11760320_at RPL31 ribosomal protein L31 Nucleus other down 0.0359 -0.4817 11757059_x_at RPL36A ribosomal protein L36a Cytoplasm other down 0.0245 -0.4892 ILMN_1781137 RPL36A down 0.0058 -0.2884 11763301_x_at RPL39 ribosomal protein L39 Cytoplasm other down 0.0015 -0.6391 ILMN_1737015 RPL39 updown 0 0 0.3728 -0.5099 11758357_x_at RPL9 ribosomal protein L9 Cytoplasm other down 0.0001 -0.6199 ILMN_1750507 RPL9 updown 0.0192 0 0.122 -0.4428 11715238_x_at RPL9 ribosomal protein L9 Cytoplasm other down 0.0171 -0.5635 11715237_s_at RPL9 ribosomal protein L9 Cytoplasm other down 0.0379 -0.4317 11723251_at RPS15A ribosomal protein S15a Cytoplasm other updown 0.0353 0 0.2228 -0.4987 ILMN_1787949 RPS15A updown 0 0 0.4652 -0.7155 11719784_x_at RPS23 ribosomal protein S23 Cytoplasm translation regulator down 0.0088 -0.3773 ILMN_1772459 RPS23 down 0 -0.2369 11744350_a_at RPS27L ribosomal protein S27-like Nucleus other updown 0.0018 0.0021 0.3056 -0.6247 ILMN_1712678 RPS27L updown 0 0.0123 0.251 -0.2258 200099_PM_s_at RPS3A ribosomal protein S3A Cytoplasm other down 0.019 -0.5249 ILMN_1673638 RPS3A updown 0 0 0.1365 -0.4609 11716320_x_at RPS3A ribosomal protein S3A Cytoplasm other down 0.0243 -0.5237 11758816_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.0019 -0.3773 ILMN_1688178 RRP7A updown 0.001 0.0003 0.1697 -0.1927 11758817_x_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.0141 -0.1061 11758818_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.0189 -0.4409 11758819_x_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.0315 -0.4415 11739217_a_at RSAD2 radical S-adenosyl methionine domain containing 2 Cytoplasm enzyme updown 0 0 -0.0216 -0.9211 ILMN_1657871 RSAD2 updown 0 0.0002 0.1604 -0.2531 RSAD2 20308629 RSAD2 (viperin) is an antiviral protein whose expression is highly upregulated during viral infections via IFN-dependent and/or IFN-independent pathways and an IRF1 mediated type I IFN independent mechanism of enhanced RSAD2 expression provides a redundan 11739216_x_at RSAD2 radical S-adenosyl methionine domain containing 2 Cytoplasm enzyme updown 0.0017 0 0.0519 -0.7221 11717539_at RYBP RING1 and YY1 binding protein Nucleus transcription regulator up 0.0046 0.5541 ILMN_1721842 RYBP up 0 0.5015 11725138_at S100A12 S100 calcium binding protein A12 Cytoplasm other updown 0.0178 0 0.1732 -0.8643 ILMN_1748915 S100A12 updown 0 0 0.2687 -0.4897 11718347_a_at S100P S100 calcium binding protein P Cytoplasm other down 0.0003 -0.5807 ILMN_1801216 S100P updown 0.0073 0 0.1025 -0.7749 11751213_s_at SCOC short coiled-coil protein Cytoplasm other down 0 -0.7469 ILMN_1768050 SCOC down 0.0072 -0.329 11757358_s_at SCOC short coiled-coil protein Cytoplasm other down 0.0003 -0.6163 11745739_a_at SCOC short coiled-coil protein Cytoplasm other down 0.0013 -0.4595 11725694_at SDPR serum deprivation response Plasma Membrane other up 0.0019 0.6003 ILMN_1715991 SDPR up 0.003 0.345 11717754_a_at SEC14L1 SEC14-like 1 (S. cerevisiae) Cytoplasm transporter up 0.0337 0.4444 ILMN_1732575 SEC14L1 updown 0 0.0111 0.3923 -0.1913 11717753_a_at SEC14L1 SEC14-like 1 (S. cerevisiae) Cytoplasm transporter up 0.0479 0.4171 11732749_at SEC14L5 SEC14-like 5 (S. cerevisiae) unknown other up 0.0065 0.4812 ILMN_1687268 SEC14L5 updown 0 0.0309 0.4909 -0.0367 11716401_a_at SELENBP1 selenium binding protein 1 Cytoplasm other up 0 0.7386 ILMN_1680652 SELENBP1 up 0.0013 0.3342 11755826_a_at SELP selectin P (granule membrane protein 140kDa, antigen CD62) Plasma Membrane other up 0.0305 0.3599 ILMN_1715417 SELP up 0.0169 0.2958 11758712_s_at SELT selenoprotein T Cytoplasm other down 0.0127 -0.5368 ILMN_1746368 SELT down 0.0062 -0.3718 11716028_x_at SELT selenoprotein T Cytoplasm other down 0.0145 -0.4869 11716027_at SELT selenoprotein T Cytoplasm other down 0.0154 -0.4535 11751845_x_at SERPING1 serpin peptidase inhibitor, clade G (C1 inhibitor), member 1 Extracellular Space other updown 0 0 0.2433 -0.7169 ILMN_1670305 SERPING1 updown 0.0018 0.0373 0.1635 -0.2186 SERPING1 17709141 A likely regulator of MASP2 11715368_a_at SERPING1 serpin peptidase inhibitor, clade G (C1 inhibitor), member 1 Extracellular Space other updown 0 0 0.1792 -0.7634 11759250_at SGSM1 small G protein signaling modulator 1 Nucleus other up 0.0003 0.7309 ILMN_1762207 SGSM1 updown 0.0499 0.0007 0.1514 -0.2408 11740156_a_at SH2D1B SH2 domain containing 1B Cytoplasm other down 0.0003 -0.4573 ILMN_1701237 SH2D1B down 0.0321 -0.2516 11740157_at SH2D1B SH2 domain containing 1B Cytoplasm other down 0.0004 -0.5894 11749207_a_at SH2D1B SH2 domain containing 1B Cytoplasm other down 0.0012 -0.487 11718446_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0 1.0035 ILMN_1762764 SH3BGRL2 up 0 0.3922 11718447_s_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0 0.8568 11718448_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0 0.6147 11718445_at SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 Plasma Membrane other up 0 0.713 11747888_a_at SH3YL1 SH3 domain containing, Ysc84-like 1 (S. cerevisiae) unknown other down 0.0431 -0.296 ILMN_1712231 SH3YL1 down 0.041 -0.2292 11757924_s_at SIPA1L2 signal-induced proliferation-associated 1 like 2 unknown other updown 0.005 0.0019 0.3981 -0.5144 ILMN_1732923 SIPA1L2 updown 0 0.0271 0.3543 -0.2427 11744184_a_at SIPA1L2 signal-induced proliferation-associated 1 like 2 unknown other updown 0.0174 0.0027 0.2931 -0.4015 11744185_a_at SIPA1L2 signal-induced proliferation-associated 1 like 2 unknown other updown 0.0244 0.0104 0.3883 -0.6165 11747774_a_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter down 0.0023 -0.5738 ILMN_1741165 SLC11A1 down 0.0002 -0.4371 11748920_x_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter down 0.0307 -0.6035 11727843_a_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter down 0.0373 -0.5083 11724454_at SLC22A4 solute carrier family 22 (organic cation/ergothioneine transporter), member 4 Plasma Membrane transporter down 0.0026 -0.5272 ILMN_1685057 SLC22A4 updown 0.009 0.0364 0.2824 -0.2266 Page 95 of 111 Diabetes

11717162_a_at SLC29A1 solute carrier family 29 (nucleoside transporters), member 1 Plasma Membrane transporter up 0.0007 0.729 ILMN_1723971 SLC29A1 updown 0 0.0025 0.4686 -0.1268 11726491_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) updown 0 0 0.6967 -0.3669 ILMN_1772809 SLC4A1 updown 0 0 0.27 -0.3488 11758430_s_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) updown 0 0.0003 0.5597 -0.0408 11726490_a_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) updown 0 0.0004 0.8056 -0.3949 11726489_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) up 0.0092 0.5157 11730162_s_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0 0.9029 ILMN_1806349 SLC6A8 up 0 0.4419 11716741_x_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0 0.8616 11730163_x_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0 0.6912 11716740_a_at SLC6A8 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 Cytoplasm transporter up 0.0022 0.5239 11716270_a_at SLIRP SRA stem-loop interacting RNA binding protein Cytoplasm other up 0.0244 0.461 ILMN_1661945 SLIRP updown 0.0046 0.0004 -0.0064 -0.3315 11741507_a_at SMOX spermine oxidase Cytoplasm enzyme updown 0 0 0.4811 -0.3807 ILMN_1775380 SMOX updown 0 0 0.3283 -0.2488 11731064_a_at SMOX spermine oxidase Cytoplasm enzyme updown 0 0.0001 0.6374 -0.177 11741508_x_at SMOX spermine oxidase Cytoplasm enzyme down 0.0045 -0.4634 11753731_x_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other updown 0.001 0.0297 0.4112 -0.2204 ILMN_1701933 SNCA updown 0 0.0002 0.3652 0.0684 SNCA 21747756 SNCA acts as a danger-associated molecular pattern that activates the expression of TLRs to initiate the proinflammatory pathway and microglial activation. 11731447_x_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other updown 0.001 0.0342 0.4661 -0.2247 ILMN_1766165 SNCA up 0.0095 0.2638 11754090_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other updown 0.0013 0.0345 0.4819 -0.2227 11739782_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other updown 0.001 0.0373 0.4649 -0.2446 11731448_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0001 0.5808 11731446_s_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0011 0.297 11753730_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other up 0.0014 0.4068 11753974_s_at SNRPG small nuclear ribonucleoprotein polypeptide G Nucleus other up 0.0351 0.4045 ILMN_1683562 SNRPG up 0.0058 0.2652 11757703_x_at SNRPG small nuclear ribonucleoprotein polypeptide G Nucleus other up 0.0466 0.4448 11730054_s_at SNX16 sorting nexin 16 unknown transporter down 0.0001 -0.6797 ILMN_1787415 SNX16 down 0 -0.4746 11730053_a_at SNX16 sorting nexin 16 unknown transporter down 0.0001 -0.5451 11721911_at SOX8 SRY (sex determining region Y)-box 8 Nucleus transcription regulator up 0.0002 0.7465 ILMN_1789244 SOX8 up 0.0183 0.2631 11736145_a_at SPATA20 spermatogenesis associated 20 unknown other up 0.0008 0.2801 ILMN_1687247 SPATA20 updown 0 0.0165 0.412 -0.1677 11721115_at SPCS3 signal peptidase complex subunit 3 homolog (S. cerevisiae) Cytoplasm peptidase down 0.0135 -0.4683 ILMN_1667707 SPCS3 updown 0.0373 0.0002 0.0347 -0.4396 11744191_x_at SPNS3 spinster homolog 3 (Drosophila) unknown other up 0.0002 0.6597 ILMN_1668984 SPNS3 updown 0.0001 0.035 0.261 -0.1844 11744190_a_at SPNS3 spinster homolog 3 (Drosophila) unknown other up 0.0002 0.6338 11746362_x_at SPNS3 spinster homolog 3 (Drosophila) unknown other up 0.0006 0.556 11716526_x_at SPON2 spondin 2, extracellular matrix protein Extracellular Space other up 0.0018 0.486 ILMN_1676099 SPON2 up 0.0115 0.1679 SPON2 20205276 SPON2 expression is upregulated during intestinal inflammation and may induce NF-kappaB promoter activation in a TLR-9 mediated manner. 11754601_s_at SPON2 spondin 2, extracellular matrix protein Extracellular Space other up 0.0031 0.3023 11716525_a_at SPON2 spondin 2, extracellular matrix protein Extracellular Space other up 0.0104 0.3833 11734826_s_at SPRED1 sprouty-related, EVH1 domain containing 1 Plasma Membrane other down 0.0001 -0.6075 ILMN_1804277 SPRED1 down 0.0017 -0.236 11734824_at SPRED1 sprouty-related, EVH1 domain containing 1 Plasma Membrane other down 0.0004 -0.5118 11734825_at SPRED1 sprouty-related, EVH1 domain containing 1 Plasma Membrane other down 0.0102 -0.3922 11722689_a_at SPTBN1 spectrin, beta, non-erythrocytic 1 Plasma Membrane other up 0.001 0.5447 ILMN_1661335 SPTBN1 up 0.001 0.3095 11716418_a_at SPTBN1 spectrin, beta, non-erythrocytic 1 Plasma Membrane other up 0.0025 0.5423 11716419_at SPTBN1 spectrin, beta, non-erythrocytic 1 Plasma Membrane other up 0.0305 0.5534 11744850_a_at SSH2 slingshot homolog 2 (Drosophila) Cytoplasm phosphatase up 0.0483 0.4747 ILMN_1672834 SSH2 up 0 0.3904 11743839_a_at ST3GAL6 ST3 beta-galactoside alpha-2,3-sialyltransferase 6 Cytoplasm enzyme down 0.0443 -0.4668 ILMN_1781560 ST3GAL6 down 0.0003 -0.2625 11726264_s_at STRADB STE20-related kinase adaptor beta Cytoplasm kinase up 0.0013 0.5809 ILMN_1701386 STRADB up 0.0008 0.2766 11720598_x_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator updown 0.0001 0 0.1485 -0.4821 ILMN_1736054 SUB1 updown 0.014 0 0.1972 -0.354 11758245_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator updown 0.0008 0.0004 0.2291 -0.4341 11751297_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.0015 -0.5528 11756654_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.0021 -0.6192 11720599_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.0094 -0.6001 11725898_s_at TAL1 T-cell acute lymphocytic leukemia 1 Nucleus transcription regulator down 0.0077 -0.2857 ILMN_1748450 TAL1 down 0.0011 -0.3227 20304918 TAX1BP1 and TNFAIP3 (A20) inhibit antiviral signalling by targeting TBK1/IKKi kinases and disrupting the TRAF3-TBK1-IKKi signalling complex. 11718272_a_at TAX1BP1 Tax1 (human T-cell leukemia virus type I) binding protein 1 Cytoplasm other down 0.0055 -0.5024 ILMN_1793118 TAX1BP1 down 0 -0.4665 TAX1BP1 21765415 TAX1BP1 phosphorylation by CHUK is pivotal for the proinflammatory cytokine-dependent assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation. (Demonstrated in mouse) 11755219_a_at THBD thrombomodulin Plasma Membrane transmembrane receptor down 0.0126 -0.4035 ILMN_1759787 THBD down 0.0002 -0.3166 17283140 TAX1BP1 is a nuclear receptor co-activator that forms a complex with the glucocorticoid receptor (NR3C1). TAX1BP1 can bind Tax, a human T-cell leukemia virus type 1 oncoprotein, directly and this induces the dissociation of TAX1BP1 from the glucocorticoid 11744390_s_at TIMM8B translocase of inner mitochondrial membrane 8 homolog B (yeast) Cytoplasm transporter down 0.0383 -0.5301 ILMN_1738938 TIMM8B down 0.0023 -0.3055 11323673 TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and its activation mobilizes the nuclear factor NF-kappaB and stimulates tumour necrosis factor-alpha (TNF) production. 11733111_a_at TLK1 tousled-like kinase 1 Nucleus kinase down 0.0251 -0.1969 ILMN_1811029 TLK1 down 0.0114 -0.1974 11489966 TLR5 expressed on the basolateral surface of intestinal epithelia mediates innate immune inflammatory responses to Salmonella by inducing epithelial pro-inflammatory gene expression. 11743123_a_at TLN1 talin 1 Plasma Membrane other up 0.0004 0.6408 ILMN_1696643 TLN1 updown 0.0004 0.0054 0.2961 -0.248 12794153 TLR5 forms heteromeric complexes with TLR4 as well as homomeric complexes. Signaling via heteromeric TLR5/TLR4 complexes is involved in the induction of macrophage nitric oxide (NO) production by Gram-negative flagellin. 11731200_a_at TLR5 toll-like receptor 5 Plasma Membrane transmembrane receptor up 0.0156 0.4215 ILMN_1722981 TLR5 up 0.0006 0.2752 TLR5 22434932 TLR5 forms a dimer upon binding to bacterial flagellin. ILMN_1822384 TLR5 up 0.0217 0.2811 22545147 TLR5 is highly expressed in mucosal dendritic cells and TLR5 signalling restricts regulatory T cell generation. (Demonstrated in mice) 11726947_a_at TLR8 toll-like receptor 8 Plasma Membrane transmembrane receptor resiquimod down 0.0345 -0.4925 ILMN_1657892 TLR8 updown 0.0319 0.016 0.2022 -0.28 TLR8 17283206 Toll-like receptor 5 (TLR5) is the TLR activated by bacterial flagellin and TLR5 residue 268 is responsible for human and mouse discrimination between flagellin molecules. 11721931_s_at TMCC2 transmembrane and coiled-coil domain family 2 Extracellular Space other up 0.0099 0.6357 ILMN_1659024 TMCC2 up 0.0052 0.2805 15069060 TLR5 engagement with its ligand, flagellin, results in the activation of MAP kinases (ERK1/2, JNK, and p38) and degradation of NFKBIA (I-kappa-B-alpha). 11744965_x_at TMCC2 transmembrane and coiled-coil domain family 2 Extracellular Space other up 0.0288 0.4657 22863420 TLR5 deficiency in mice leads to a transient inability to manage proteobacteria which promotes chronic gut inflammation. (Demonstrated in mouse) 11762892_at TMCO1 transmembrane and coiled-coil domains 1 unknown other down 0.0004 -0.746 ILMN_1793829 TMCO1 updown 0.045 0 0.1135 -0.4844 17264163 TLR8 signalling strongly promotes inflammatory lipid mediator biosynthesis, providing novel insights on innate immune response to viral infections. 11731400_s_at TMCO1 transmembrane and coiled-coil domains 1 unknown other down 0.0021 -0.6589 20652908 TLR8 is activated in human monocytic cells following Helicobacter pylori phagocytosis and TLR8 single nucleotide polymorphism play a role in the modulation of TLR8-dependent microbicidal response of infected macrophages. 11731401_a_at TMCO1 transmembrane and coiled-coil domains 1 unknown other down 0.0052 -0.6391 21734241 TLR7 and TLR8 are translocated from the endoplasmic reticulum to the endosome in the presence of antiphospholipid antibodies, as a consequence, plasmacytoid dendritic cells become dramatically sensitized to TLR7/8 agonists and this may play a role in syst 11731402_at TMCO1 transmembrane and coiled-coil domains 1 unknown other down 0.0399 -0.4905 14579267 Toll-like receptor 8 (TLR8), 7 and 9 form a functional subgroup within the TLR family that recognizes pathogen-associated molecular patterns in endosomal/lysosomal compartments. 11752680_a_at TMEM135 transmembrane protein 135 Cytoplasm other down 0.016 -0.5262 ILMN_1700202 TMEM135 down 0.0479 -0.29 22753494 TLR8 binds to exosomal MIR21 and MIR29A secreted by tumour cells and initiates a prometastatic inflammatory response. 11745789_a_at TMEM135 transmembrane protein 135 Cytoplasm other down 0.0228 -0.4703 14976262 TLR8 and TLR7 bind single-stranded RNA, stimulating dendritic cells (DCs) and macrophages to secrete interferon-alpha and pro-inflammatory, as well as regulatory, cytokines. 11752681_s_at TMEM135 transmembrane protein 135 Cytoplasm other down 0.0239 -0.3233 18985539 TLR8 expression and function is highly up-regulated in colonic epithelium from patients with active inflammatory bowel disease (IBD), suggesting that TLR8 signalling is important in the pathogenesis of IBD. 11751628_a_at TMEM140 transmembrane protein 140 unknown other down 0.014 -0.4152 ILMN_1736863 TMEM140 down 0 -0.3519 22393042 TLR8 binding of HIV ssRNA induces endosomal acidification and chromatin remodeling at the TNF-alpha promoter to promote TNF-alpha release in infected macrophages. 11724275_s_at TMEM158 transmembrane protein 158 (gene/pseudogene) Plasma Membrane other updown 0 0.0369 0.8196 -0.3302 ILMN_1792455 TMEM158 updown 0 0.0023 0.5778 -0.1453 11720217_a_at TMEM176A transmembrane protein 176A unknown other updown 0.0263 0 -0.4161 -0.8649 ILMN_1791511 TMEM176A updown 0.0386 0 -0.1004 -0.4176 11732501_a_at TMOD1 tropomodulin 1 Cytoplasm enzyme up 0.022 0.4439 ILMN_1736911 TMOD1 up 0.0006 0.3247 11721098_x_at TMX1 thioredoxin-related transmembrane protein 1 Cytoplasm enzyme down 0.0216 -0.3993 ILMN_1691181 TMX1 updown 0.011 0 0.2608 -0.4611 11721097_at TMX1 thioredoxin-related transmembrane protein 1 Cytoplasm enzyme down 0.0404 -0.4951 11743636_at TNFAIP6 tumor necrosis factor, alpha-induced protein 6 Extracellular Space other updown 0.001 0 0.2692 -0.7565 ILMN_1785732 TNFAIP6 updown 0 0.0002 0.409 -0.234 11751841_a_at TNFRSF17 tumor necrosis factor receptor superfamily, member 17 Plasma Membrane other updown 0 0.0009 0.6056 -0.1445 ILMN_1768016 TNFRSF17 updown 0.0063 0.0123 0.0493 -0.1512 11716559_x_at TNS1 tensin 1 Plasma Membrane other updown 0 0 0.7586 -0.3833 ILMN_1807919 TNS1 updown 0 0.002 0.5 -0.1647 11745268_a_at TNS1 tensin 1 Plasma Membrane other updown 0 0 0.838 -0.6072 11716558_at TNS1 tensin 1 Plasma Membrane other updown 0 0 0.7181 -0.3418 11716556_a_at TNS1 tensin 1 Plasma Membrane other updown 0 0.0061 0.5028 -0.0727 11716557_a_at TNS1 tensin 1 Plasma Membrane other updown 0.0025 0.015 0.5557 -0.358 11727649_a_at TOMM5 translocase of outer mitochondrial membrane 5 homolog (yeast) Cytoplasm other down 0.0041 -0.5397 ILMN_1808661 TOMM5 updown 0.0159 0.013 0.0923 -0.3118 21555403 TREM1 expression is upregulated following Pseudomonas aeruginosa infection in the cornea and the inhibition of TREM1 reduces the severity of corneal disease. TREM1 acts as an inflammatory amplifier in P. aeruginosa keratitis by modulating TLR signalling a 11743578_x_at TOMM5 translocase of outer mitochondrial membrane 5 homolog (yeast) Cytoplasm other down 0.0049 -0.4511 21393102 TREM1 is an activating receptor expressed on neutrophils and monocytes that amplifies inflammation induced by TLR4-signalling, specifically in the induction of TNFA production. 11720970_at TOP2A topoisomerase (DNA) II alpha 170kDa Nucleus enzyme novobiocin, etoposide,down CPI-0004Na, pixantrone, becatecarin, elsamitrucin,0.0015 AQ4N, BN 80927,-0.5542 tafluposide, ILMN_1686097 mitoxantrone,TOP2A norfloxacin, dexrazoxane,down tirapazamine, TAS-103, gatifloxacin,0.0037 valrubicin, gemifloxacin, -0.2285nemorubicin, nalidixic acid, epirubicin,22459945 doxorubicin, TREM1 daunorubicin mediates endotoxin tolerance in monocytes through its ability to induce anti- or pro-inflammatory signals depending on its membrane-bound state. 11720971_at TOP2A topoisomerase (DNA) II alpha 170kDa Nucleus enzyme novobiocin, etoposide,down CPI-0004Na, pixantrone, becatecarin, elsamitrucin,0.0484 AQ4N, BN 80927,-0.414 tafluposide, mitoxantrone, norfloxacin, dexrazoxane, tirapazamine, TAS-103, gatifloxacin, valrubicin, gemifloxacin, nemorubicin, nalidixic acid, epirubicin,20797396 doxorubicin, TREM1 daunorubicin is a superimmunoglobulin receptor present on neutrophils and monocytes, which plays an important role in the amplification of inflammation and its expression is inhibited by PGD(2) and PGJ(2) in macrophages. 11716399_at TP53INP2 tumor protein p53 inducible nuclear protein 2 Nucleus other up 0.0155 0.5209 ILMN_1686906 TP53INP2 updown 0 0.0262 0.3739 -0.131 21690199 TREM1 expression is induced by vitamin D3 in human bronchial epithelial cells. Activation of TREM1 leads to the induction of human beta defensin 2 and TNF-alpha mRNA in the airway epithelium. 11746721_a_at TREM1 triggering receptor expressed on myeloid cells 1 Plasma Membrane other down 0.0077 -0.5518 ILMN_1688231 TREM1 down 0.0216 -0.2371 TREM1 23475790 TREM1 expression and shedding are regulated by CpG-mediated TLR9 activation in macrophages. 11746560_a_at TREML1 triggering receptor expressed on myeloid cells-like 1 Plasma Membrane other up 0 0.7298 ILMN_1690783 TREML1 up 0.0214 0.2395 11750170_a_at TRIM22 tripartite motif containing 22 Cytoplasm transcription regulator down 0.0228 -0.3388 ILMN_1779252 TRIM22 updown 0.0081 0 0.1519 -0.2558 TRIM22 19218198 An E3 ubiquitin ligase that ubiquitinates the viral 3C protease and acts as a component of an antiviral pathway induced by IFN against picornaviruses 11722369_x_at TRIM22 tripartite motif containing 22 Cytoplasm transcription regulator down 0.0278 -0.3579 11736582_a_at TRIM36 tripartite motif containing 36 Cytoplasm other down 0.009 -0.517 ILMN_1668453 TRIM36 down 0.0167 -0.2735 TRIM36 23438823 TRIM36 was identified in a systematic screen for positive regulators of innate immune responses. 11722902_a_at TRMT13 tRNA methyltransferase 13 homolog (S. cerevisiae) unknown other down 0.0161 -0.4703 ILMN_1659786 TRMT13 down 0.0002 -0.3322 11722543_at TRPC1 transient receptor potential cation channel, subfamily C, member 1 Plasma Membrane ion channel down 0.0286 -0.4321 ILMN_1674380 TRPC1 down 0.0391 -0.2283 11721184_at TSPAN33 tetraspanin 33 Plasma Membrane other up 0.0145 0.5219 ILMN_1749403 TSPAN33 up 0.0004 0.3345 11749969_a_at TSPAN5 tetraspanin 5 Plasma Membrane other up 0.0043 0.6783 ILMN_1799028 TSPAN5 updown 0 0.0097 0.4062 -0.1068 11717082_a_at TSPAN9 tetraspanin 9 Plasma Membrane other up 0.0001 0.5787 ILMN_1729453 TSPAN9 up 0 0.4669 11759710_at TXNDC9 thioredoxin domain containing 9 unknown other down 0.0003 -0.6156 ILMN_1731137 TXNDC9 down 0.0005 -0.2983 11754067_a_at TXNDC9 thioredoxin domain containing 9 unknown other down 0.0054 -0.628 11731479_s_at TXNDC9 thioredoxin domain containing 9 unknown other down 0.02 -0.5675 11730895_at UBA6 ubiquitin-like modifier activating enzyme 6 Cytoplasm enzyme down 0.0022 -0.6786 ILMN_1675085 UBA6 down 0.0196 -0.2237 11738859_s_at UBXN6 UBX domain protein 6 Cytoplasm other up 0.0244 0.5856 ILMN_1658624 UBXN6 updown 0 0.0439 0.4567 -0.0777 11733901_a_at UQCRQ ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5kDa Cytoplasm enzyme updown 0.028 0.0047 0.0421 -0.5572 ILMN_1666471 UQCRQ updown 0.0014 0 0.1571 -0.5127 11739800_a_at VCPIP1 valosin containing protein (p97)/p47 complex interacting protein 1 Cytoplasm peptidase down 0.0336 -0.5198 ILMN_1682180 VCPIP1 down 0.0368 -0.2926 11732665_a_at VSTM1 V-set and transmembrane domain containing 1 unknown other up 0.0009 0.7766 ILMN_1763455 VSTM1 up 0 0.4384 11756497_a_at VWCE von Willebrand factor C and EGF domains unknown other updown 0 0.0311 1.1275 -0.2081 ILMN_1760315 VWCE updown 0 0.006 0.5714 -0.2001 11751281_a_at VWCE von Willebrand factor C and EGF domains unknown other up 0 1.0898 11747666_a_at WARS tryptophanyl-tRNA synthetase Cytoplasm enzyme updown 0.0051 0.0266 0.4851 -0.5438 ILMN_1727271 WARS updown 0 0.0003 0.4536 -0.3154 11743471_a_at WDFY3 WD repeat and FYVE domain containing 3 Cytoplasm enzyme down 0.0048 -0.5766 ILMN_1697493 WDFY3 down 0.0174 -0.3261 11743470_a_at WDFY3 WD repeat and FYVE domain containing 3 Cytoplasm enzyme down 0.0066 -0.5821 11735912_a_at WDFY3 WD repeat and FYVE domain containing 3 Cytoplasm enzyme down 0.0071 -0.4428 11743469_a_at WDFY3 WD repeat and FYVE domain containing 3 Cytoplasm enzyme down 0.0145 -0.4773 11736518_a_at WHSC1 Wolf-Hirschhorn syndrome candidate 1 Nucleus enzyme down 0.0452 -0.4409 ILMN_1663502 WHSC1 down 0.0001 -0.4023 11745018_a_at WLS wntless homolog (Drosophila) Cytoplasm other up 0.0188 0.6085 ILMN_1660549 WLS up 0.003 0.2442 11743281_a_at WNK1 WNK lysine deficient protein kinase 1 Cytoplasm kinase up 0.0007 0.4929 ILMN_1876924 WNK1 up 0.0203 0.2971 11749370_x_at XAF1 XIAP associated factor 1 Nucleus other down 0.0197 -0.2037 ILMN_1742618 XAF1 updown 0.0154 0.0002 0.095 -0.2106 11747630_a_at XAF1 XIAP associated factor 1 Nucleus other down 0.0227 -0.1672 11747631_x_at XAF1 XIAP associated factor 1 Nucleus other down 0.0314 -0.1855 11717368_x_at ZC3HAV1 zinc finger CCCH-type, antiviral 1 Plasma Membrane other up 0.028 0.5433 ILMN_1729973 ZC3HAV1 up 0.0122 0.258 ZC3HAV1 21102435 ZC3HAV1 isoform ZAPS is selectively induced by 5'-triphosphate-modified RNA and functions as a potent stimulator of interferon responses via the RIG-I signalling pathway. 11721521_at ZDHHC17 zinc finger, DHHC-type containing 17 Cytoplasm enzyme down 0.0072 -0.5949 ILMN_1697153 ZDHHC17 down 0.0003 -0.3193 11721520_at ZDHHC17 zinc finger, DHHC-type containing 17 Cytoplasm enzyme down 0.0472 -0.4222 11751981_a_at ZMYM1 zinc finger, MYM-type 1 unknown other down 0.0188 -0.4429 ILMN_1702763 ZMYM1 down 0.016 -0.1625 11739953_at ZNF14 zinc finger protein 14 Nucleus transcription regulator down 0.0481 -0.5062 ILMN_1692145 ZNF14 updown 0.0257 0.0308 0.1929 -0.2088 11743149_at ZNF22 zinc finger protein 22 Nucleus other down 0.0447 -0.2757 ILMN_1798533 ZNF22 down 0 -0.2937 11731362_a_at ZNF624 zinc finger protein 624 Nucleus other down 0.0026 -0.6548 ILMN_1670122 ZNF624 down 0.0044 -0.28 11745146_a_at ZNF624 zinc finger protein 624 Nucleus other down 0.0044 -0.4964 11729517_a_at ZNF644 zinc finger protein 644 Nucleus other down 0.0086 -0.5975 ILMN_1730118 ZNF644 down 0.0428 -0.2881 11729261_a_at ZNF644 zinc finger protein 644 Nucleus other down 0.0303 -0.5577 11729465_x_at ZNF816 zinc finger protein 816 unknown other down 0.0072 -0.6009 ILMN_1728710 ZNF816 down 0.0052 -0.2494 11732579_s_at ZNF880 zinc finger protein 880 unknown other up 0.0041 0.2883 ILMN_1773367 ZNF880 up 0.0413 0.1452 11728652_x_at ZRANB2 zinc finger, RAN-binding domain containing 2 Nucleus transcription regulator down 0.0387 -0.5459 ILMN_1662383 ZRANB2 down 0.0004 -0.3081 Diabetes Page 96 of 111

Differentially expressed genes at T1D diagnosis (FDR < 0.05) showing concordant changes in Affymetrix and Illumina arrays, and information regarding the innate immunity function of the genes (InnateDB)

AFFYMETRIX Case vs. control ILLUMINA Case vs. control InnateDB (www.innatedb.org) Innate Immunity Genes in human. P value for overlap is 0.00000071. Affymetrix ID Gene Symbol (IPA) Gene name (IPA) Location (IPA) Type (IPA) Drug (IPA) Change probeset FDR max FDR min SLR max SLR min Illumina ID Gene Symbol (IPA) Change probeFDR max FDR min SLR max SLR min Gene Symbol (human)Pubmed ID Annotation 11736635_a_at AAK1 AP2 associated kinase 1 Cytoplasm kinase up 0.0148 0.2712 ILMN_1688755 AAK1 up 0.0057 0.1804 11756406_x_at ADM adrenomedullin Extracellular Space other down 0.0008 -0.4279 ILMN_1708934 ADM down 0.0012 -0.1451 11753618_a_at ADM adrenomedullin Extracellular Space other down 0.0032 -0.4169 11716710_a_at ADM adrenomedullin Extracellular Space other down 0.0092 -0.3517 11739641_a_at AFAP1 actin filament associated protein 1 Cytoplasm other up 0.0229 0.2757 ILMN_1701998 AFAP1 up 0.0161 0.0423 11733383_a_at AFAP1 actin filament associated protein 1 Cytoplasm other up 0.035 0.1752 11727638_a_at AHI1 Abelson helper integration site 1 Cytoplasm other up 0.013 0.2833 ILMN_1791006 AHI1 up 0.0219 0.1258 11715711_a_at AKR1C3 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase,Cytoplasm type II) enzyme up 0.0201 0.0704 ILMN_1713124 AKR1C3 up 0.0185 -0.0273 11734503_x_at ALOX15 arachidonate 15-lipoxygenase Cytoplasm enzyme updown 0.0391 0.0002 -0.11 -0.11 ILMN_2403534 ALOX15 updown 0.0009 0.0005 0.1507 0.1507 11750808_a_at ALOX15 arachidonate 15-lipoxygenase Cytoplasm enzyme down 0.0002 -0.0273 11750344_a_at ALOX15 arachidonate 15-lipoxygenase Cytoplasm enzyme down 0.0014 -0.1735 11750919_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase down 0.0002 -0.2366 ILMN_1701603 ALPL down 0 -0.2119 11748032_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase down 0.0011 -0.327 11748031_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase down 0.0025 -0.1117 11729337_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase down 0.0035 -0.0753 11729336_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase down 0.006 -0.0551 11740441_a_at APOBEC3A apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A Cytoplasm enzyme down 0.0268 -0.2403 ILMN_1680192 APOBEC3A down 0.0002 -0.2022 APOBEC3A 20615867 APOBEC3A has deaminase activity in monocytes and macrophages and this induces high levels of TC-specific deaminase activity in IFN-alpha signalling. 11725701_a_at AQP9 aquaporin 9 Plasma Membrane transporter down 0.0112 -0.2905 ILMN_1715068 AQP9 down 0.0033 -0.1208 11749906_a_at AQP9 aquaporin 9 Plasma Membrane transporter down 0.0363 -0.229 11728909_s_at B3GALTL beta 1,3-galactosyltransferase-like unknown other down 0.031 -0.2276 ILMN_1764813 B3GALTL down 0.0138 -0.061 11730096_a_at BCL2A1 BCL2-related protein A1 Cytoplasm other down 0 -0.4226 ILMN_1769229 BCL2A1 down 0.0158 -0.0713 BCL2A1 21167304 BCL2A1 negatively regulates autophagy and expression of BCL2A1 in Mycobacterium tuberculosis infected macrophages provides the bacteria a survival strategy to overcome host defences. 11734979_at BTNL3 butyrophilin-like 3 unknown other down 0 -0.322 ILMN_1783795 BTNL3 down 0 -0.3488 11734978_at BTNL3 butyrophilin-like 3 unknown other down 0 -0.4846 11736058_s_at C10orf32 chromosome 10 open reading frame 32 unknown other down 0.0362 -0.0841 ILMN_2151056 C10orf32 down 0.0001 -0.2558 11755220_a_at C17orf97 chromosome 17 open reading frame 97 unknown other up 0.0116 -0.136 ILMN_1707137 C17orf97 up 0.0024 0.0262 11730006_at C19orf18 chromosome 19 open reading frame 18 unknown other up 0.0244 0.2573 ILMN_1785933 C19orf18 up 0.0316 0.1927 11725888_at C19orf59 chromosome 19 open reading frame 59 unknown other down 0 -0.4668 ILMN_1762713 C19orf59 down 0 -0.4906 11725889_at C19orf59 chromosome 19 open reading frame 59 unknown other down 0.0011 -0.3548 22031815 LL-37 (CAMP) reduces influenza A viral load and disease severity in mice. 11738455_a_at C20orf197 chromosome 20 open reading frame 197 unknown other down 0.0152 -0.1907 ILMN_1691228 C20orf197 down 0.0021 -0.1881 21832078 CAMP expression is induced upon endoplasmic reticulum stress via NF-kB-C/EBP-alpha activation. 11738456_s_at C20orf197 chromosome 20 open reading frame 197 unknown other down 0.0277 -0.193 21448240 CAMP (LL-37), at sufficiently low concentrations, is able to reduce fungal infectivity by inhibiting C. albicans adhesion to plastic surfaces, oral epidermoid cells, and the urinary bladders of female mice. The inhibitory effects of LL-37 on cell adhesion 11757208_s_at C22orf34 chromosome 22 open reading frame 34 unknown other up 0.0023 0.3378 ILMN_1717371 C22orf34 up 0 0.3135 21562230 CAMP (LL-37) confers protective immunity against psoriasis by neutralizing cytosolic DNA in keratinocytes and blocking the formation of AIM2 inflammasomes. 11730513_a_at C7orf53 chromosome 7 open reading frame 53 unknown other down 0.0064 -0.4321 ILMN_1804895 C7orf53 down 0.0005 -0.2963 21762664 CAMP protects against colitis induction in mice. The increased expression of CAMP in monocytes involves the activation of TLR9/ERK signalling pathway by bacterial DNA. (Demonstrated in mouse) 11758239_s_at C9orf72 chromosome 9 open reading frame 72 unknown other down 0.0206 -0.2206 ILMN_1741881 C9orf72 down 0.0001 -0.1422 23328115 CAMP (LL-37) is downregulated during septic shock. 11726688_at CAMP cathelicidin antimicrobial peptide Cytoplasm other down 0.0007 -0.2745 ILMN_1688580 CAMP down 0.0002 -0.2116 CAMP 21464330 CAMP (LL-37) translocates across the E. coli outer membrane and halts bacterial growth by interfering cell wall biogenesis. 11723012_a_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0031 -0.2012 ILMN_1768870 CAPZA2 down 0.0278 -0.2001 19625657 CAMP represents a potent antimicrobial and cell-stimulating agent, most abundantly expressed in peripheral organs such as lung and skin during inflammation. 11723013_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0049 -0.3918 19748465 CAMP, a protein that has direct antimicrobial activity, serves as a mediator of vitamin D3-induced autophagy. 11750192_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0079 -0.3438 19812202 CAMP (LL-37) modulates IFN-gamma responses during both the innate and adaptive phases of immune responses, indicating an immunomodulatory role for this endogenous peptide. 11747046_x_at CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2 Cytoplasm other down 0.0268 -0.317 18397922 CAMP induces endothelium-dependent relaxation in human omental veins, or vasodilation, mediated via an effect on endothelial ALX. 11731726_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase down 0.0002 0.0378 ILMN_1722158 CASP5 down 0.0091 -0.1109 18923446 CAMP is involved in various aspects of skin biology, including protection against infection, wound healing, and also in psoriasis where it suppresses apoptosis in keratinocytes. 11753343_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase down 0.0006 -0.1377 20036634 CAMP has dual function as an antimicrobial agent against bacterial target cells and a cell penetrating peptide that can deliver nucleic acids into the host cells. 11731727_x_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase down 0.0013 -0.1129 19797203 CAMP has both antimicrobial and regenerative capabilities and promotes high glucose-attenuated epithelial wound healing via EGFR transactivation in organ cultured corneas. 11744442_at CCDC82 coiled-coil domain containing 82 unknown other down 0.0268 -0.312 ILMN_1791933 CCDC82 down 0.0353 -0.1387 20163451 CAMP decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs) and this inhibition is dependent on phosphorylation of extracellular signal-regulated kinase (ERK). Vitamin C attenuates ERK signalling to inhibit the regulat 11736416_s_at CCDC82 coiled-coil domain containing 82 unknown other down 0.0303 -0.2505 20190140 CAMP and human beta-defensins (hBDs) antimicrobial peptides induce the secretion of a pruritogenic cytokine IL-31 by human mast cells. 11728039_s_at CCL8 chemokine (C-C motif) ligand 8 Extracellular Space cytokine up 0.0092 0.0023 ILMN_1772964 CCL8 up 0.0034 0.1119 21441450 CAMP (LL-37) dramatically reduced TNFA and nitric oxide levels produced by LPS and IFNG-polarized M1 macrophages, in addition LL-37-treated M1 macrophages were more efficient at suppressing tumour growth in vitro. This demonstrates the selective ability o 11729741_x_at CD68 CD68 molecule Plasma Membrane other up 0.0109 0.1397 ILMN_2359907 CD68 up 0.001 0.0616 20610648 CAMP (LL37) directs macrophage differentiation toward macrophages with a pro-inflammatory signature and this requires internalization of the peptide, resulting in low production of IL-10 and profound production of IL-12p40 upon LPS stimulation. 11750359_x_at CD68 CD68 molecule Plasma Membrane other up 0.041 0.2128 19703986 CAMP (LL37) converts self-RNA into a trigger of TLR7 and TLR8 in human dendritic cells (DC), leading to production of TNF-alpha and IL6 and the differentiation of myeloid DCs into mature DCs. 11723679_s_at CD69 CD69 molecule Plasma Membrane transmembrane receptor down 0.044 -0.2564 ILMN_2188333 CD69 updown 0.042 0.0122 -0.0634 -0.0634 21393634 CAMP (LL-37) attenuates lethal sepsis/endotoxin shock by suppressing the LPS-induced apoptosis of vascular and hepatic endothelial cells. LL-37 was found to inhibit the binding of LPS to the LPS receptors expressed on the cells. 11760081_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0 -0.5585 ILMN_1664330 CEACAM1 down 0.0005 -0.3069 CEACAM1 21389264 CAMP (LL37) is found in high concentrations within neutrophil extracellular traps (NETs). CAMP is a neutrophil protein that facilitates the uptake and recognition of mammalian DNA by plasmacytoid dendritic cells, and may play a role in Systemic Lupus Erth 11751094_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0007 -0.4517 20042575 CAMP enhances delivery of CpG oligodeoxynucleotides to stimulate immune cells and this is independent of its amphipathic structure and its bactericidal property. 11756058_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0021 -0.3474 18836450 CEACAM1 inhibits TLR2 induced pro-inflammatory immune responses by inducing PTPN6-(SHP-1)-mediated inhibition of the PI3K-NF-kappaB signal transduction pathway in pulmonary epithelial cells. 11751217_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0026 -0.4502 11753506_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0031 -0.3224 11723283_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0035 -0.2068 11751095_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)Plasma Membrane other down 0.0043 -0.4044 11758261_s_at CEP55 centrosomal protein 55kDa Cytoplasm other down 0.002 -0.2129 ILMN_1747016 CEP55 down 0.0062 -0.1498 11720247_a_at CEP55 centrosomal protein 55kDa Cytoplasm other down 0.0048 0.0228 11725980_at CFD complement factor D (adipsin) Extracellular Space peptidase down 0 -1.116 ILMN_1777190 CFD updown 0.0135 0 -0.6887 -0.6887 11730536_at CHST13 carbohydrate (chondroitin 4) sulfotransferase 13 Cytoplasm enzyme down 0.0003 -0.1645 ILMN_1734707 CHST13 down 0.0094 -0.1846 11727473_at CLC Charcot-Leyden crystal protein Cytoplasm enzyme down 0.0015 -0.1918 ILMN_1654875 CLC down 0 -0.3329 11753241_s_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other updown 0.0466 0.0018 -0.2008 -0.2008 ILMN_2292178 CLEC12A updown 0.0088 0.0068 0.0347 0.0347 11762101_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other updown 0.0135 0.0334 -0.0132 -0.0132 ILMN_1663142 CLEC12A down 0.0002 -0.2406 11729479_a_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other down 0.0117 -0.3058 11724885_at CLIC3 chloride intracellular channel 3 Nucleus ion channel up 0.0029 0.4036 ILMN_1796423 CLIC3 up 0 0.313 11726437_a_at CMTM8 CKLF-like MARVEL transmembrane domain containing 8 Extracellular Space cytokine up 0.0388 0.2613 ILMN_1710124 CMTM8 up 0.0297 0.0442 11734956_a_at CNTNAP2 contactin associated protein-like 2 Plasma Membrane other down 0.0038 -0.1159 ILMN_1690223 CNTNAP2 down 0.0004 -0.0557 11715694_at COX7B cytochrome c oxidase subunit VIIb Cytoplasm enzyme down 0 -0.2762 ILMN_2184049 COX7B down 0.0005 -0.2039 11715695_x_at COX7B cytochrome c oxidase subunit VIIb Cytoplasm enzyme down 0 -0.416 11715349_a_at COX7C cytochrome c oxidase subunit VIIc Cytoplasm enzyme down 0.014 -0.3845 ILMN_1798189 COX7C down 0.0001 -0.3097 11735847_a_at CPA5 carboxypeptidase A5 Extracellular Space peptidase up 0.0002 0.1439 ILMN_1791530 CPA5 up 0.0009 0.0763 11726485_at CPED1 cadherin-like and PC-esterase domain containing 1 Cytoplasm other down 0.0163 -0.0472 ILMN_1677038 CPED1 down 0.0001 -0.2936 11749604_s_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.0074 -0.2923 ILMN_1736190 CYP4F3 down 0.0328 -0.1021 11733297_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.0339 -0.1483 11750945_x_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.0373 -0.1973 11749605_x_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.04 -0.2782 11733296_s_at CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3 Cytoplasm enzyme down 0.0422 -0.1035 11716580_s_at CYSTM1 cysteine-rich transmembrane module containing 1 unknown other down 0.0002 -0.5052 ILMN_1761566 CYSTM1 down 0 -0.2816 11716579_a_at CYSTM1 cysteine-rich transmembrane module containing 1 unknown other down 0.0007 -0.5037 11741500_a_at DAGLB diacylglycerol lipase, beta Plasma Membrane enzyme up 0.0084 0.2343 ILMN_1658885 DAGLB up 0.0281 0.1072 11720934_a_at DAGLB diacylglycerol lipase, beta Plasma Membrane enzyme up 0.0313 0.2024 11743972_a_at DDIT4 DNA-damage-inducible transcript 4 Cytoplasm other up 0.0013 0.4507 ILMN_1661599 DDIT4 up 0 0.3617 11721438_s_at DEFA1 (includes others) defensin, alpha 1 Cytoplasm other updown 0.0001 0.0002 0.0072 0.0072 ILMN_2193213 DEFA1 (includes others) updown 0 0 -0.3736 -0.3736 ILMN_1679357 DEFA1 (includes others) updown 0 0 -0.3425 -0.3425 ILMN_1725661 DEFA1 (includes others) updown 0 0 -0.3799 -0.3799 ILMN_2165289 DEFA1 (includes others) updown 0 0 -0.3578 -0.3578 ILMN_2102721 DEFA1 (includes others) updown 0 0 -0.4433 -0.4433 11724330_s_at DGCR8 DiGeorge syndrome critical region gene 8 Nucleus enzyme up 0.0193 0.1216 ILMN_1694223 DGCR8 updown 0.0399 0.0051 -0.1761 -0.1761 11723899_a_at DHRS9 dehydrogenase/reductase (SDR family) member 9 Cytoplasm enzyme down 0.0006 -0.3567 ILMN_1733998 DHRS9 down 0 -0.3458 11737096_a_at DSC2 desmocollin 2 Plasma Membrane other down 0.0001 -0.513 ILMN_1663119 DSC2 down 0.0015 -0.1599 11725531_a_at DSC2 desmocollin 2 Plasma Membrane other down 0.0001 -0.4788 11757702_s_at DSC2 desmocollin 2 Plasma Membrane other down 0.0011 -0.2711 11750862_a_at EMR3 egf-like module containing, mucin-like, hormone receptor-like 3 Plasma Membrane G-protein coupled receptor down 0.0074 -0.2878 ILMN_2348487 EMR3 down 0.0123 0.0107 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase up 0.0234 0.3011 ILMN_1743145 ERAP2 up 0 0.5042 ILMN_2123312 ERAP2 up 0.0228 0.1403 11762512_a_at ERICH1 glutamate-rich 1 unknown other up 0.0019 0.3844 ILMN_1904238 ERICH1 up 0 0.4032 11726321_a_at ERO1L ERO1-like (S. cerevisiae) Cytoplasm enzyme down 0.0076 -0.3237 ILMN_1744963 ERO1L down 0.0066 -0.1539 11733841_a_at EVI2A ecotropic viral integration site 2A Plasma Membrane transmembrane receptor down 0.0059 -0.2467 ILMN_2369018 EVI2A down 0 -0.2909 ILMN_1733579 EVI2A down 0 -0.3039 11746669_a_at FAM118A family with sequence similarity 118, member A unknown other updown 0.0177 0.0001 -0.091 -0.091 ILMN_1809147 FAM118A updown 0.0121 0.0003 -0.0074 -0.0074 11720023_a_at FAM118A family with sequence similarity 118, member A unknown other updown 0.0351 0.0015 -0.0995 -0.0995 11740946_at FAM153B family with sequence similarity 153, member B unknown other up 0.0022 0.2423 ILMN_1798557 FAM153B up 0.0001 0.2875 11761206_at FAM153B family with sequence similarity 153, member B unknown other up 0.0031 0.0962 11734736_a_at FAR1 fatty acyl CoA reductase 1 Cytoplasm enzyme down 0.0297 -0.2894 ILMN_2143250 FAR1 down 0.0013 -0.1905 11728532_at FCER1A Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide Plasma Membrane transmembrane receptor down 0.0015 -0.4101 ILMN_1688423 FCER1A down 0 -0.2905 11716486_at FCGBP Fc fragment of IgG binding protein Extracellular Space other up 0.0002 0.5779 ILMN_2302757 FCGBP up 0 0.5135 11736312_s_at FCGR1A Fc fragment of IgG, high affinity Ia, receptor (CD64) Plasma Membrane transmembrane receptor updown 0.0033 0.0006 -0.1475 -0.1475 ILMN_2176063 FCGR1A updown 0.0148 0.0003 -0.1491 -0.1491 FCGR1A 21044955 FCGR1A (FcgammaRI) is a receptor that recognizes IgG opsonized particles and initiates phagocytosis in immune clearance. FCGR1A is also a negative regulator of complement-mediated phagocytosis. 11736311_x_at FCGR1A Fc fragment of IgG, high affinity Ia, receptor (CD64) Plasma Membrane transmembrane receptor updown 0.0262 0.0013 -0.2602 -0.2602 11756362_x_at FCGR1B Fc fragment of IgG, high affinity Ib, receptor (CD64) Plasma Membrane transmembrane receptor down 0.0005 -0.1829 ILMN_2261600 FCGR1B down 0.0014 -0.1135 11724171_a_at FCHO2 FCH domain only 2 Cytoplasm other down 0.0002 -0.4265 ILMN_1670322 FCHO2 down 0.0005 -0.1832 11724172_s_at FCHO2 FCH domain only 2 Cytoplasm other down 0.0112 -0.2307 11762375_a_at FCRL5 Fc receptor-like 5 unknown other down 0.0055 -0.2878 ILMN_1684445 FCRL5 down 0.0142 -0.1424 11750086_s_at FGFBP2 fibroblast growth factor binding protein 2 Extracellular Space other up 0.0332 -0.1557 ILMN_1761945 FGFBP2 updown 0.0015 0.0055 -0.1135 -0.1135 11743306_at FHDC1 FH2 domain containing 1 unknown other down 0 -0.5754 ILMN_1699206 FHDC1 down 0.0185 -0.1929 11723696_at FLI1 Friend leukemia virus integration 1 Nucleus transcription regulator up 0.0275 -0.1137 ILMN_1665738 FLI1 up 0.0082 0.0664 FLI1 20879862 FLI1 contributes to lipopolysaccharide (LPS)-induced expression of matrix metalloprotease 1 (MMP-1), MMP-3, MMP-10, and interleukin-10 (IL-10) and rapid down-regulation of FLI1 expression after LPS stimulation attenuates the induction of various MMPs and 11744141_x_at FOLR3 folate receptor 3 (gamma) Extracellular Space other down 0 -0.6333 ILMN_1730454 FOLR3 down 0 -0.3801 11744140_a_at FOLR3 folate receptor 3 (gamma) Extracellular Space other down 0 -0.5476 11762622_at FPR1 formyl peptide receptor 1 Plasma Membrane G-protein coupled receptor down 0.0264 -0.2869 ILMN_2092118 FPR1 down 0.0002 -0.3225 11734034_a_at FPR2 formyl peptide receptor 2 Plasma Membrane G-protein coupled receptor down 0.014 -0.2327 ILMN_2392569 FPR2 down 0.0017 -0.2529 11739140_a_at FPR2 formyl peptide receptor 2 Plasma Membrane G-protein coupled receptor down 0.0478 -0.2839 ILMN_1740875 FPR2 down 0.0354 -0.176 11745309_a_at FRMD3 FERM domain containing 3 unknown other up 0.0081 0.2902 ILMN_1698725 FRMD3 up 0.0005 0.1068 11750746_a_at FRMD3 FERM domain containing 3 unknown other up 0.0351 0.134 11736092_at GCA grancalcin, EF-hand calcium binding protein Cytoplasm other down 0.0107 -0.1721 ILMN_1800602 GCA down 0.0308 -0.1166 11721010_a_at GDPD5 glycerophosphodiester phosphodiesterase domain containing 5 unknown other up 0.0093 0.3313 ILMN_1701643 GDPD5 up 0.0044 0.2335 11734201_s_at GK glycerol kinase Cytoplasm kinase down 0.045 -0.1397 ILMN_2393296 GK down 0.0194 -0.15 ILMN_1725471 GK down 0.0414 -0.0172 11724166_a_at GLT25D2 glycosyltransferase 25 domain containing 2 unknown other up 0.0012 0.2541 ILMN_1736742 GLT25D2 up 0 0.0024 11724167_s_at GLT25D2 glycosyltransferase 25 domain containing 2 unknown other up 0.0019 0.2091 11722379_at GNG11 guanine nucleotide binding protein (G protein), gamma 11 Plasma Membrane enzyme down 0.002 -0.2958 ILMN_1782419 GNG11 down 0.0413 -0.0271 11756632_a_at GNLY granulysin Cytoplasm other up 0.0076 0.1298 ILMN_1708779 GNLY updown 0 0.0358 0.1573 0.1573 11751857_a_at GNLY granulysin Cytoplasm other up 0.0129 0.1065 ILMN_1790692 GNLY up 0 0.1802 11763715_a_at GNLY granulysin Cytoplasm other up 0.013 0.1392 11763756_x_at GNLY granulysin Cytoplasm other up 0.0149 0.1249 11763755_a_at GNLY granulysin Cytoplasm other up 0.0186 -0.0281 11716395_a_at GPR56 G protein-coupled receptor 56 Plasma Membrane G-protein coupled receptor up 0 0.3561 ILMN_2384122 GPR56 updown 0 0.026 0.1267 0.1267 ILMN_2352097 GPR56 up 0 0.1995 11719246_a_at GSTT1 glutathione S-transferase theta 1 Cytoplasm enzyme up 0.0305 0.1238 ILMN_1730054 GSTT1 up 0.0061 0.2145 11755052_s_at GYPE glycophorin E (MNS blood group) Plasma Membrane other up 0.0007 0.0907 ILMN_1695187 GYPE up 0.003 0.0508 11724900_a_at GZMB granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1) Cytoplasm peptidase up 0.0009 0.2696 ILMN_2109489 GZMB up 0 0.4022 11728125_a_at GZMH granzyme H (cathepsin G-like 2, protein h-CCPX) Cytoplasm peptidase up 0.0022 0.2612 ILMN_1731233 GZMH up 0 0.1962 11752202_a_at HAL histidine ammonia-lyase Cytoplasm enzyme down 0.0102 -0.3766 ILMN_2074748 HAL down 0.0005 -0.2718 11725439_at HBD hemoglobin, delta Cytoplasm transporter down 0 -0.4355 ILMN_1815527 HBD down 0.0208 -0.1534 11725438_a_at HBD hemoglobin, delta Cytoplasm transporter down 0.0002 -0.404 11758698_x_at HBG1 hemoglobin, gamma A Cytoplasm other down 0.0017 -0.062 ILMN_1796678 HBG1 updown 0 0.0002 0.1917 0.1917 11744478_s_at HBG2 hemoglobin, gamma G Cytoplasm other down 0 -0.2331 ILMN_2084825 HBG2 updown 0 0 -0.0549 -0.0549 11758696_x_at HBG2 hemoglobin, gamma G Cytoplasm other down 0 -0.249 11755537_s_at HBG2 hemoglobin, gamma G Cytoplasm other down 0 -0.232 11715494_s_at HBG2 hemoglobin, gamma G Cytoplasm other down 0 -0.2188 11724835_s_at HCAR3 hydroxycarboxylic acid receptor 3 Plasma Membrane G-protein coupled receptor down 0.0044 -0.2304 ILMN_1677693 HCAR3 down 0.0002 -0.343 11755386_a_at HDC histidine decarboxylase Cytoplasm enzyme down 0 -0.3644 ILMN_1792323 HDC updown 0.0028 0 -0.2111 -0.2111 11755374_a_at HERC5 HECT and RLD domain containing E3 ubiquitin protein ligase 5 Cytoplasm enzyme down 0.0326 0.0029 ILMN_1729749 HERC5 updown 0.0143 0.0087 0.0171 0.0171 HERC5 20308324 HERC5 positively regulates the innate antiviral responses by sustaining IRF3 activation via a novel post-translational modification, ISGylation. 11728152_a_at HIST1H2BD histone cluster 1, H2bd Nucleus other down 0 -0.6093 ILMN_1758623 HIST1H2BD down 0.0002 -0.3748 11724021_at HIST1H2BD histone cluster 1, H2bd Nucleus other down 0.0002 -0.4657 ILMN_1651496 HIST1H2BD down 0.0003 -0.1887 11728153_x_at HIST1H2BD histone cluster 1, H2bd Nucleus other down 0.0002 -0.577 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other updown 0.0002 0.0027 -0.0959 -0.0959 ILMN_2165753 HLA-A updown 0.0353 0 -0.242 -0.242 11762119_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other updown 0.0002 0.0266 0.0399 0.0399 ILMN_2203950 HLA-A down 0.0005 0.003 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other updown 0.0021 0.0006 0.0459 0.0459 ILMN_1721113 HLA-C updown 0.0019 0.0006 -0.0474 -0.0474 11761071_at HLA-DOB major histocompatibility complex, class II, DO beta Plasma Membrane transmembrane receptor down 0.0185 -0.2692 ILMN_1700428 HLA-DOB down 0.0003 -0.3225 11750528_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor down 0.0113 -0.0276 ILMN_1808405 HLA-DQA1 down 0.0067 -0.1655 11724799_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor down 0.0469 -0.0173 11755998_x_at HLA-DRB4 major histocompatibility complex, class II, DR beta 4 Plasma Membrane transmembrane receptor down 0.0077 -0.0167 ILMN_2159694 HLA-DRB4 down 0.0018 -0.1455 ILMN_1752592 HLA-DRB4 down 0.0308 -0.1047 11725869_at HOXC4 homeobox C4 Nucleus transcription regulator up 0.0422 0.3042 ILMN_1719975 HOXC4 up 0.0397 0.1243 11757480_x_at IFI27 interferon, alpha-inducible protein 27 Cytoplasm other updown 0.0019 0.002 -0.0604 -0.0604 ILMN_2058782 IFI27 updown 0 0.0175 0.0703 0.0703 IFI27 20939681 IFI27 is a mitochondrial protein and its expression sensitizes cells to apoptotic stimuli via mitochondrial membrane destabilization. 11715893_s_at IFI27 interferon, alpha-inducible protein 27 Cytoplasm other up 0.0059 -0.0506 11760254_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0232 0.0007 0.0389 0.0389 ILMN_1760062 IFI44 updown 0 0.0007 0.1445 0.1445 11748003_a_at IFI44 interferon-induced protein 44 Cytoplasm other updown 0.0177 0.006 0.0988 0.0988 11719886_a_at IFI44 interferon-induced protein 44 Cytoplasm other up 0.0313 0.2904 11723236_at IFI44L interferon-induced protein 44-like unknown other updown 0.0019 0.0016 0.1411 0.1411 ILMN_1723912 IFI44L updown 0 0.0457 0.1769 0.1769 11723234_at IFI44L interferon-induced protein 44-like unknown other updown 0.0017 0.0108 0.2403 0.2403 11723235_a_at IFI44L interferon-induced protein 44-like unknown other updown 0.0041 0.0248 0.2204 0.2204 11756820_a_at IFIT1 interferon-induced protein with tetratricopeptide repeats 1 Cytoplasm other down 0.0032 0.0391 ILMN_1707695 IFIT1 updown 0 0 -0.0185 -0.0185 IFIT1 20386592 IFIT1 expression activates the IFN response during C. pneumoniae infection, mediated by intracellular nucleotide-sensing pattern recognition receptors (PRRs), which operate through a mechanism dependent on the bacterial type III secretion system (T3SS). 11721873_at IFIT2 interferon-induced protein with tetratricopeptide repeats 2 Cytoplasm other down 0.0064 0.04 ILMN_1739428 IFIT2 down 0.0024 -0.0631 IFIT2 22745654 IFIT1 is an innate immune network bottleneck with the ability to suppress induction of TLR4 response genes in LPS-stimulated macrophages. (Demonstrated in mice) 11731407_x_at IFIT3 interferon-induced protein with tetratricopeptide repeats 3 Cytoplasm other down 0.0201 0.031 ILMN_1701789 IFIT3 updown 0.0003 0 -0.0143 -0.0143 IFIT3 21642987 IFIT1 recognizes and directly binds to 5'-triphosphate RNA and functions as an innate inhibitor of viral replication and pathogenicity. (Demonstrated in murine model) Page 97 of 111 Diabetes

11715239_x_at IFITM3 interferon induced transmembrane protein 3 Plasma Membrane other down 0.0157 -0.186 ILMN_1805750 IFITM3 updown 0.0044 0 -0.3423 -0.3423 IFITM3 22065572 IFIT2 expression imparts anti-viral immunity to restrict West Nile virus infection and control viral pathogenesis. (Demonstrated in mice) 11735989_s_at IGJ immunoglobulin J polypeptide, linker protein for immunoglobulin alpha and muExtracellular polypeptides Space other down 0.0499 -0.3492 ILMN_2105441 IGJ down 0.0149 -0.2006 19108715 IFIT2 belongs to type 1 interferon response genes and is highly induced after stimulation with LPS and selectively affects LPS induced protein expression by regulation at different post-transcriptional levels. 11732017_a_at IL18RAP interleukin 18 receptor accessory protein Plasma Membrane transmembrane receptor down 0.004 -0.3003 ILMN_1721762 IL18RAP down 0.0004 -0.1281 21813773 IFIT3 triggers host antiviral responses by bridging TBK1 to MAVS, and IFIT3 plays an important role in the activation of IRF3. 11753566_a_at IL5RA interleukin 5 receptor, alpha Plasma Membrane transmembrane receptor down 0.0015 -0.0781 ILMN_1863116 IL5RA down 0.0053 -0.1503 20601941 IFITM3 is post-translationally regulated by S-palmitoylation on membrane-proximal cysteines, which controls its clustering in membrane compartments and its antiviral activity against influenza virus. 11734541_a_at IL5RA interleukin 5 receptor, alpha Plasma Membrane transmembrane receptor down 0.0216 0.0383 20064371 IFITM3 is an antiviral restriction factor that mediates cellular resistance to influenza A H1N1 virus, West Nile virus, and Dengue virus. 11718841_s_at IL8 interleukin 8 Extracellular Space cytokine down 0.0003 -0.3425 ILMN_2184373 IL8 down 0.0001 -0.1864 IL8 17220369 IL8 is produced by airway epithelial cells in response to invading bacteria and mediates airway epithelial defence against bacterial infection via the DUOX1-TACE-TGF-alpha-EGFR signalling pathway. 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator updown 0.0013 0 -0.2245 -0.2245 ILMN_2312606 IRF5 updown 0.0357 0 -0.3802 -0.3802 IRF5 18332133 IRF5 is activated by both TBK1 and MYD88 to form a homodimer that binds to and activates transcription of type I interferon and inflammatory cytokine genes. ILMN_1670576 IRF5 down 0 -0.5479 12600985 IRF5 can act as both an activator and a repressor of interferon (IFN) gene induction dependent on the IRF-interacting partner, and may be a part of the regulatory network that ensures timely expression of the immediate early inflammatory genes. 11755311_a_at ITGB1BP1 integrin beta 1 binding protein 1 Plasma Membrane other up 0.0307 0.3701 ILMN_1690099 ITGB1BP1 up 0.0043 0.2443 22412986 Phosphorylation of IRF5 at ser451 and ser462 is the primary trigger of IRF5 function in nuclear accumulation, transcription and apoptosis. 11732454_at KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 Plasma Membrane ion channel down 0.0068 -0.3049 ILMN_1675756 KCNJ15 down 0.0087 -0.1713 11732455_at KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 Plasma Membrane ion channel down 0.0483 -0.1564 ILMN_2396903 KCNJ15 down 0.0277 -0.0959 11724676_a_at KLHL2 kelch-like 2, Mayven (Drosophila) Cytoplasm transporter down 0.007 -0.3056 ILMN_1701837 KLHL2 down 0.0227 -0.129 11740450_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor up 0.0495 0.1128 ILMN_1799134 KLRD1 up 0 0.2792 11740669_x_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor up 0.0022 0.3686 ILMN_2055781 KLRF1 up 0.0102 0.0982 11753219_a_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor up 0.0032 0.4404 11745699_a_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor up 0.0051 0.2998 11740668_a_at KLRF1 killer cell lectin-like receptor subfamily F, member 1 Plasma Membrane transmembrane receptor up 0.0066 0.2335 11723952_at KRT1 keratin 1 Cytoplasm other up 0 0.1581 ILMN_1735712 KRT1 up 0.0122 0.1275 11740592_a_at KRT72 keratin 72 unknown other up 0.0008 0.3982 ILMN_1695812 KRT72 up 0 0.4122 11749876_a_at LAMP2 lysosomal-associated membrane protein 2 Plasma Membrane enzyme down 0.0216 -0.3481 ILMN_2243687 LAMP2 down 0.0212 -0.1591 11721243_a_at LAP3 leucine aminopeptidase 3 Cytoplasm peptidase up 0.0286 0.2598 ILMN_1683792 LAP3 up 0.0394 0.0135 11757634_a_at LCN2 lipocalin 2 Extracellular Space transporter down 0.0026 0.0432 ILMN_1692223 LCN2 down 0.0022 -0.131 11746636_a_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.0109 0.3425 ILMN_1904481 LEF1 up 0 0.4596 11747931_a_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.0271 0.3022 11736566_a_at LEF1 lymphoid enhancer-binding factor 1 Nucleus transcription regulator up 0.035 0.3678 11730656_a_at LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), memberExtracellular 3 Space other down 0.0011 -0.1927 ILMN_1661631 LILRA3 down 0 -0.304 ILMN_1786303 LILRA3 down 0.0199 -0.1833 19840871 LY96 (MD-2) recognizes only exogenous pathogen-associated molecular patterns (PAMPs) when complexed with TLR2-CD14 or TLR4-CD14. 11734144_s_at LRRC37A3 (includes others)leucine rich repeat containing 37, member A3 unknown other up 0.0247 0.1417 ILMN_1783673 LRRC37A3 (includes others)up 0.0349 0.0924 15852007 LY86 and CD180 interact directly with the TLR4 signalling complex, inhibiting its ability to bind microbial ligand. 11715419_at LY6E lymphocyte antigen 6 complex, locus E Plasma Membrane other up 0.0192 -0.0597 ILMN_1695404 LY6E up 0.0019 -0.0725 10359581 LY96 is physically associated with TLR4 on the cell surface and confers responsiveness to lipopolysaccharide (LPS). 11728507_at LY96 lymphocyte antigen 96 Plasma Membrane other down 0.0015 -0.3263 ILMN_1724533 LY96 down 0.0002 -0.0595 LY96 22433852 Amino acid Phe126 of LY96 acts as a hydrophobic switch driving agonist-dependent contacts necessary for TLR4 dimerization and activation. 11728644_a_at MLC1 megalencephalic leukoencephalopathy with subcortical cysts 1 Plasma Membrane transporter up 0.0487 0.285 ILMN_1747725 MLC1 up 0.0102 0.1918 22474354 Morphine binds to LY96, triggering TLR4 oligomerization and induces neuroinflammation within the central nervous system. 11751744_a_at MMD monocyte to macrophage differentiation-associated Plasma Membrane other up 0.0302 0.2617 ILMN_1733937 MMD up 0.0214 0.1381 21712422 TLR4::LY96 functions as intracellular LPS sensor and triggers a unique set of LPS responses upon recognition of phagocytosed bacteria in macrophages. (Demonstrated in murine model) 11719657_a_at MMP9 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)Extracellular Space peptidase down 0.0471 -0.2939 ILMN_1796316 MMP9 down 0.0007 -0.2989 MMP9 21873432 MMP9 and NEU1 cross-talk in alliance with TLR4 on the cell surface is a novel membrane sialidase-controlling mechanism that depends on ligand binding to its Toll-like receptor (TLR) to induce NEU1 activity, to influence receptor desialylation and subseque 11754705_a_at MRPL43 mitochondrial ribosomal protein L43 Cytoplasm translation regulator down 0.0115 -0.1037 ILMN_1652147 MRPL43 down 0.0387 -0.1458 22496659 MMP9 inhibits influenza virus pathogenesis by mediating neutrophil migration to the respiratory tract. (Demonstrated in mice) 11737424_at MS4A2 membrane-spanning 4-domains, subfamily A, member 2 Plasma Membrane transmembrane receptor down 0 -0.328 ILMN_1806721 MS4A2 down 0.0387 -0.2387 22860023 MMP9 cleaves the pulmonary collectin SFTPD (SP-D) leading to loss of its innate immune functions. (Demonstrated in mouse) 11732452_a_at MS4A3 membrane-spanning 4-domains, subfamily A, member 3 (hematopoietic cell-specific)Plasma Membrane other down 0 -0.5887 ILMN_1695530 MS4A3 down 0.0012 -0.1859 18062906 MX1 is an interferon-induced member of the dynamin superfamily of large GTPases, which inhibit a wide range of viruses by blocking an early stage of the replication cycle. 11716167_a_at MX1 myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse)Nucleus enzyme down 0.0269 -0.1773 ILMN_1662358 MX1 updown 0.0084 0.002 -0.0468 -0.0468 MX1 22531919 MX1 expression is upregulated by alpha-defensins in gigival epithelial cell. 11725136_a_at MYOM2 myomesin (M-protein) 2, 165kDa Cytoplasm other up 0 1.0678 ILMN_1716733 MYOM2 up 0 1.0668 20538602 MX1 GTPase is a key mediator of cell-autonomous innate immunity against a broad range of viruses such as influenza and bunyaviruses. 11743110_at NAMPT nicotinamide phosphoribosyltransferase Extracellular Space cytokine down 0.0449 -0.2959 ILMN_1653871 NAMPT down 0.0007 -0.0215 NAMPT 22377803 NAMPT secretion is enhanced by extracellular ATP in LPS-primed monocytes. ILMN_1753111 NAMPT down 0.0026 -0.297 11763960_a_at NDUFB3 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa Cytoplasm enzyme down 0 -0.3902 ILMN_2119945 NDUFB3 down 0.0003 -0.2709 11717159_a_at NDUFB3 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa Cytoplasm enzyme down 0 -0.495 ILMN_2119937 NDUFB3 down 0.0005 -0.1381 11764061_s_at NDUFB3 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa Cytoplasm enzyme down 0.0034 -0.2088 11725210_s_at NFXL1 nuclear transcription factor, X-box binding-like 1 Nucleus transcription regulator up 0.013 -0.0736 ILMN_1682197 NFXL1 up 0.0243 0.1734 11731035_a_at NLRP7 NLR family, pyrin domain containing 7 Extracellular Space other up 0.0277 0.2903 ILMN_1652366 NLRP7 up 0.0015 0.2879 NLRP7 15817483 NLRP7 is a member of the PYRIN-containing apoptotic protease-activating factor-1-like proteins that functions as a feedback regulator of CASP1-dependent interleukin-1beta secretion. 11761655_at NPCDR1 nasopharyngeal carcinoma, down-regulated 1 unknown other up 0 0.4889 ILMN_1780774 NPCDR1 up 0.0176 0.1526 11740891_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme updown 0.0235 0.0208 0.1053 0.1053 ILMN_1658247 OAS1 updown 0.0016 0 -0.2931 -0.2931 OAS1 23319625 OAS1 is a cytoplasmic dsRNA sensor. 11724255_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme updown 0.0072 0.0292 0.313 0.313 ILMN_1675640 OAS1 updown 0.007 0.0493 0.0231 0.0231 21190483 OAS1 is a pathogen recognition receptor for the viral pathogen-associated molecular pattern, double-stranded RNA. Upon recognition of dsRNA, the OAS1 activates RNASEL to cleave ssRNA. The OAS/RNASEL pathway triggers the RIG-I pathway and induce IFNB produ ILMN_2410826 OAS1 updown 0.0175 0.0065 -0.169 -0.169 11723698_a_at OAS3 2-5-oligoadenylate synthetase 3, 100kDa Cytoplasm enzyme updown 0.0258 0.0096 -0.2528 -0.2528 ILMN_1745397 OAS3 updown 0.0149 0.0121 -0.0723 -0.0723 OAS3 21190483 OAS3 is a pathogen recognition receptor for the viral pathogen-associated molecular pattern, double-stranded RNA. Upon recognition of dsRNA, the OAS3 activates RNASEL to cleave ssRNA. The OAS/RNASEL pathway triggers the RIG-I pathway and induce IFNB produ 11723699_s_at OAS3 2-5-oligoadenylate synthetase 3, 100kDa Cytoplasm enzyme down 0.0431 -0.1736 11726364_x_at OASL 2-5-oligoadenylate synthetase-like Cytoplasm enzyme up 0.0066 0.0376 ILMN_1674811 OASL up 0.0017 0.216 11736090_a_at OLIG2 oligodendrocyte lineage transcription factor 2 Nucleus transcription regulator down 0.0205 -0.1503 ILMN_1727567 OLIG2 down 0 -0.3974 11744905_x_at ORM1 orosomucoid 1 Extracellular Space other down 0 -0.3408 ILMN_1696584 ORM1 down 0.0299 -0.0735 11744904_a_at ORM1 orosomucoid 1 Extracellular Space other down 0 -0.3562 11754065_x_at ORM1 orosomucoid 1 Extracellular Space other down 0 -0.2949 11758794_x_at ORM1 orosomucoid 1 Extracellular Space other down 0.0002 -0.0668 11761414_x_at ORM1 orosomucoid 1 Extracellular Space other down 0.0216 -0.298 11738092_a_at PDE9A phosphodiesterase 9A Cytoplasm enzyme up 0.0183 0.3643 ILMN_2306540 PDE9A up 0.0178 0.2409 20418257 PGLYRP1 is a secreted innate immunity protein that is expressed in polymorphonuclear leukocytes and is conserved from insects to mammals, it recognizes bacterial peptidoglycan, and functions in antibacterial immunity and inflammation. 11732642_at PGLYRP1 peptidoglycan recognition protein 1 Plasma Membrane transmembrane receptor down 0.0002 -0.5084 ILMN_1704870 PGLYRP1 down 0 -0.5037 PGLYRP1 21602801 PGLYRP1 binds to Gram-positive bacterial wall and activates a protein-sensing two-component system to induce bacterial death. PLGYRP1-mediated activation results in membrane depolarization and cessation of peptidoglycan, protein, and RNA/DNA synthesis, as 11756898_a_at PGM5 phosphoglucomutase 5 Cytoplasm enzyme down 0.0006 0.3686 ILMN_1781388 PGM5 down 0.0111 -0.0209 21134971 PGLYRP1 is a peptidoglycan recognition protein and play a role in innate immunity against L. monocytogenes infection by inducing TNFA. (Demonstrated in murine model) ILMN_1709590 PGM5 down 0.0277 -0.1788 21439073 PGLYRP1 is a member of the Peptidoglycan Recognition Proteins (PGRP) family and recognizes peptidoglycan, a structural component of bacterial cell walls, as a part of innate immune response against infections. 11724792_a_at PGS1 phosphatidylglycerophosphate synthase 1 Cytoplasm enzyme down 0.0247 -0.0766 ILMN_2075051 PGS1 down 0.0003 -0.1867 11721650_at PI3 peptidase inhibitor 3, skin-derived Extracellular Space other down 0 -0.4486 ILMN_1693192 PI3 down 0 -0.4112 11724510_at PMAIP1 phorbol-12-myristate-13-acetate-induced protein 1 Cytoplasm other down 0.0021 -0.1661 ILMN_2098446 PMAIP1 down 0.0033 -0.1305 PMAIP1 21698224 PMAIP1 is induced by the RIG-I/MDA5 axis during viral infection and activates apoptosis in macrophages, dendritic cells and primary lymphocytes. 11724509_a_at PMAIP1 phorbol-12-myristate-13-acetate-induced protein 1 Cytoplasm other down 0.0074 -0.2686 11732808_a_at PROK2 prokineticin 2 Extracellular Space other down 0 -0.8824 ILMN_1775257 PROK2 down 0 -0.6218 11732809_a_at PROK2 prokineticin 2 Extracellular Space other down 0.0007 -0.5284 11731941_at PRSS33 protease, serine, 33 Extracellular Space peptidase down 0.0064 -0.002 ILMN_1736831 PRSS33 down 0.0014 0.0039 11761869_at PSIP1 PC4 and SFRS1 interacting protein 1 Nucleus other up 0.0157 0.1945 ILMN_1679319 PSIP1 up 0.0297 0.1913 11724037_at PTGS2 prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)Cytoplasm enzyme acetaminophen/pentazocine,down acetaminophen/clemastine/pseudoephedrine,0.032 aspirin/butalbital/caffeine,-0.1488 ILMN_2054297 acetaminophen/caffeine/dihydrocodeine,PTGS2 down aspirin/hydrocodone, aspirin/oxycodone,0.0005 acetaminophen/aspirin/caffeine,-0.1464 PTGS2 aspirin/pravastatin, acetaminophen/dexbrompheniramine/pseudoephedrine,18955820 PTGS2 (COX-2) is suppressed through inhibiting aspirin/meprobamate, the NF-kappaB activation aspirin/caffeine/propoxyphene, by LPS and this may be associated aspirin/butalbital/caffeine/codeine, with the anti-inflammatory effects aspirin/caffeine/dihydrocodeine, of L. casei on Raw264.7 cells. chlorpheniramine/ibuprofen/pseudoephedrine, licofelone, menatetrenone, suprofen, tiaprofenic acid, tenoxicam, naproxen/sumatriptan, ibuprofen/phenylephrine/chlorpheniramine, diclofenac/misoprostol, acetaminophen/butalbital/caffeine, hydrocodone/ibuprofen, acetaminophen/hydrocodone, acetaminophen/tramadol, acetaminophen/codeine, acetaminophen/oxycodone, acetaminophen/propoxyphene, nitroaspirin, ketoprofen, diclofenac, naproxen, meclofenamic acid, meloxicam, celecoxib, dipyrone, acetaminophen, mefenamic acid, diflunisal, ibuprofen, GW406381X, indomethacin, sulfasalazine, piroxicam, valdecoxib, aspirin, zomepirac, rof ILMN_1677511 PTGS2 down 0.0405 -0.1882 11721420_a_at RAP1GAP2 RAP1 GTPase activating protein 2 Cytoplasm other down 0.0139 -0.1658 ILMN_2041236 RAP1GAP2 down 0.0003 -0.1015 11749458_a_at RAP1GAP2 RAP1 GTPase activating protein 2 Cytoplasm other down 0.0338 -0.0945 11740390_a_at RBM47 RNA binding motif protein 47 unknown other down 0.0092 -0.391 ILMN_1689046 RBM47 down 0.0055 -0.2648 11725237_a_at RBPMS2 RNA binding protein with multiple splicing 2 unknown other up 0 0.6187 ILMN_1808238 RBPMS2 up 0 0.3681 11755653_a_at RFX2 regulatory factor X, 2 (influences HLA class II expression) Nucleus transcription regulator down 0.0019 -0.6434 ILMN_2396287 RFX2 down 0 -0.3385 11739797_a_at RFX2 regulatory factor X, 2 (influences HLA class II expression) Nucleus transcription regulator down 0.0207 -0.4056 ILMN_1706357 RFX2 down 0 -0.2816 11729758_at RGS18 regulator of G-protein signaling 18 Cytoplasm other down 0.0266 -0.2722 ILMN_2101278 RGS18 down 0.0009 -0.2566 11755743_a_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme down 0 -0.5095 ILMN_1730628 RNASE2 down 0.0001 -0.3154 11729772_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme down 0 -0.4544 11720349_at ROPN1L rhophilin associated tail protein 1-like Cytoplasm kinase down 0.0014 -0.4846 ILMN_1696466 ROPN1L down 0.0013 -0.3176 11726119_at RPGR retinitis pigmentosa GTPase regulator Cytoplasm other down 0.0423 -0.1059 ILMN_1768097 RPGR down 0.0279 -0.1766 11757329_s_at RPL26 ribosomal protein L26 Cytoplasm other down 0.0072 -0.2303 ILMN_1731546 RPL26 updown 0.0392 0 -0.3516 -0.3516 11757027_x_at RPL31 ribosomal protein L31 Nucleus other down 0.0188 -0.2716 ILMN_1754195 RPL31 updown 0.0014 0 -0.4019 -0.4019 11757421_x_at RPL31 ribosomal protein L31 Nucleus other down 0.0216 -0.2904 11763301_x_at RPL39 ribosomal protein L39 Cytoplasm other down 0.0069 -0.2603 ILMN_1737015 RPL39 updown 0.0294 0 -0.4225 -0.4225 11758357_x_at RPL9 ribosomal protein L9 Cytoplasm other down 0.0092 -0.2643 ILMN_1729033 RPL9 down 0 -0.3423 ILMN_1750507 RPL9 down 0.0001 -0.2825 ILMN_2408415 RPL9 updown 0.0011 0.0001 -0.2135 -0.2135 11723251_at RPS15A ribosomal protein S15a Cytoplasm other down 0.0071 -0.1181 ILMN_1787949 RPS15A down 0 -0.4183 11758880_at RPS15A ribosomal protein S15a Cytoplasm other down 0.0205 -0.2773 ILMN_2255310 RPS15A down 0 -0.414 ILMN_2337241 RPS15A updown 0.0029 0.0018 -0.3052 -0.3052 11744334_x_at RPS17/RPS17L ribosomal protein S17 Cytoplasm other down 0.0217 -0.1914 ILMN_2207539 RPS17/RPS17L updown 0.0235 0 -0.4869 -0.4869 ILMN_2207533 RPS17/RPS17L updown 0.0266 0.0001 -0.3727 -0.3727 11719784_x_at RPS23 ribosomal protein S23 Cytoplasm translation regulator down 0.0141 -0.1271 ILMN_1772459 RPS23 down 0 -0.3352 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other down 0 -0.5493 ILMN_2209027 RPS26 down 0 -0.638 11736193_a_at RRM2B ribonucleotide reductase M2 B (TP53 inducible) Nucleus enzyme triapine, hydroxyureadown 0.0064 -0.341 ILMN_2170595 RRM2B down 0.0032 0.0834 11758819_x_at RRP7A ribosomal RNA processing 7 homolog A (S. cerevisiae) Cytoplasm other down 0.0134 -0.3859 ILMN_1688178 RRP7A updown 0.0102 0.0009 0.1077 0.1077 11739217_a_at RSAD2 radical S-adenosyl methionine domain containing 2 Cytoplasm enzyme updown 0.0054 0.0001 -0.08 -0.08 ILMN_1657871 RSAD2 updown 0.0024 0.0004 -0.0081 -0.0081 RSAD2 20308629 RSAD2 (viperin) is an antiviral protein whose expression is highly upregulated during viral infections via IFN-dependent and/or IFN-independent pathways and an IRF1 mediated type I IFN independent mechanism of enhanced RSAD2 expression provides a redundan 11739216_x_at RSAD2 radical S-adenosyl methionine domain containing 2 Cytoplasm enzyme updown 0.0294 0.0012 0.0427 0.0427 11744411_s_at RSL24D1 ribosomal L24 domain containing 1 Nucleus other down 0.004 -0.215 ILMN_2175465 RSL24D1 down 0.0003 -0.0787 11745760_x_at RSL24D1 ribosomal L24 domain containing 1 Nucleus other down 0.0073 -0.0068 11717539_at RYBP RING1 and YY1 binding protein Nucleus transcription regulator up 0.0033 0.4408 ILMN_1721842 RYBP up 0 0.3386 11717538_a_at RYBP RING1 and YY1 binding protein Nucleus transcription regulator up 0.042 0.2566 11725138_at S100A12 S100 calcium binding protein A12 Cytoplasm other down 0.0006 -0.43 ILMN_1748915 S100A12 down 0.0001 -0.253 11718347_a_at S100P S100 calcium binding protein P Cytoplasm other down 0 -0.655 ILMN_1801216 S100P down 0 -0.7772 11732749_at SEC14L5 SEC14-like 5 (S. cerevisiae) unknown other up 0.0129 0.2467 ILMN_1687268 SEC14L5 up 0.0088 0.0972 11757025_s_at SERPINF1 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derivedExtracellular factor), Spacemember 1 other up 0.0011 0.4799 ILMN_2141482 SERPINF1 up 0.0393 0.0786 11757026_x_at SERPINF1 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derivedExtracellular factor), Spacemember 1 other up 0.0061 0.3406 11716014_a_at SERPINF1 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derivedExtracellular factor), Spacemember 1 other up 0.0066 0.2744 11756312_a_at SERPINF1 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derivedExtracellular factor), Spacemember 1 other up 0.0233 0.301 11756313_x_at SERPINF1 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derivedExtracellular factor), Spacemember 1 other up 0.0259 0.3353 11737749_a_at SGK1 serum/glucocorticoid regulated kinase 1 Cytoplasm kinase down 0.0499 -0.3341 ILMN_1702487 SGK1 down 0.0136 -0.1871 11747774_a_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter down 0.0031 -0.39 ILMN_1741165 SLC11A1 down 0 -0.4414 ILMN_1735737 SLC11A1 down 0.0022 0.0253 11739044_s_at SLC15A2 solute carrier family 15 (H+/peptide transporter), member 2 Plasma Membrane transporter down 0.0059 -0.2479 ILMN_2211739 SLC15A2 down 0.0112 -0.2532 11724454_at SLC22A4 solute carrier family 22 (organic cation/ergothioneine transporter), member 4 Plasma Membrane transporter down 0.0272 -0.2992 ILMN_2050911 SLC22A4 down 0 -0.2389 ILMN_1685057 SLC22A4 down 0.0001 -0.425 11739214_at SLC25A23 solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 23 Cytoplasm transporter up 0.0211 0.3786 ILMN_1679949 SLC25A23 up 0.0055 0.0573 11729677_a_at SLC26A8 solute carrier family 26, member 8 Plasma Membrane transporter down 0.0003 -0.365 ILMN_1755843 SLC26A8 down 0.0001 -0.1979 11754821_s_at SLC38A1 solute carrier family 38, member 1 Plasma Membrane transporter up 0.0064 0.3418 ILMN_1769911 SLC38A1 up 0 0.3722 11726491_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) down 0.0041 -0.3319 ILMN_1772809 SLC4A1 down 0.0296 -0.1115 11758430_s_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) down 0.0134 -0.2724 11726490_a_at SLC4A1 solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane proteinPlasma band Membrane 3, Diego blood transporter group) down 0.0287 -0.1835 11716033_at SLPI secretory leukocyte peptidase inhibitor Cytoplasm other down 0 -0.9587 ILMN_2114720 SLPI down 0.0002 -0.3046 11741508_x_at SMOX spermine oxidase Cytoplasm enzyme down 0.0072 -0.159 ILMN_2367258 SMOX down 0.0015 -0.1049 11741507_a_at SMOX spermine oxidase Cytoplasm enzyme down 0.0085 -0.1103 ILMN_1775380 SMOX down 0.0442 -0.0262 11731064_a_at SMOX spermine oxidase Cytoplasm enzyme down 0.0096 -0.0452 11753730_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other down 0.0042 -0.4378 ILMN_1701933 SNCA updown 0.0118 0.0196 -0.1078 -0.1078 SNCA 21747756 SNCA acts as a danger-associated molecular pattern that activates the expression of TLRs to initiate the proinflammatory pathway and microglial activation. 11731446_s_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other down 0.0092 -0.3488 11754090_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other down 0.0103 -0.3221 11753731_x_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other down 0.013 -0.4016 11739782_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other down 0.017 -0.2056 11731448_a_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other down 0.0256 -0.2885 11731447_x_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other down 0.0257 -0.3054 11756527_a_at SNX10 sorting nexin 10 Cytoplasm transporter down 0.0137 -0.3194 ILMN_2170949 SNX10 down 0.0089 -0.1895 11751097_x_at SNX10 sorting nexin 10 Cytoplasm transporter down 0.0152 -0.3392 11730053_a_at SNX16 sorting nexin 16 unknown transporter down 0.0071 0.041 ILMN_1787415 SNX16 down 0.0007 -0.1434 11730054_s_at SNX16 sorting nexin 16 unknown transporter down 0.0098 0.0226 11740248_s_at SPAG1 sperm associated antigen 1 Cytoplasm other down 0.0162 -0.1886 ILMN_2367681 SPAG1 down 0.0001 -0.3869 11740420_s_at SPAG1 sperm associated antigen 1 Cytoplasm other down 0.0387 -0.1666 11736145_a_at SPATA20 spermatogenesis associated 20 unknown other up 0 0.271 ILMN_1687247 SPATA20 up 0 0.2187 11754601_s_at SPON2 spondin 2, extracellular matrix protein Extracellular Space other up 0 0.5487 ILMN_1676099 SPON2 up 0.0019 0.1264 SPON2 20205276 SPON2 expression is upregulated during intestinal inflammation and may induce NF-kappaB promoter activation in a TLR-9 mediated manner. 11716526_x_at SPON2 spondin 2, extracellular matrix protein Extracellular Space other up 0 0.4399 11716525_a_at SPON2 spondin 2, extracellular matrix protein Extracellular Space other up 0.0002 0.5098 11734826_s_at SPRED1 sprouty-related, EVH1 domain containing 1 Plasma Membrane other down 0.0034 -0.376 ILMN_1804277 SPRED1 down 0.008 -0.0067 11716418_a_at SPTBN1 spectrin, beta, non-erythrocytic 1 Plasma Membrane other up 0.0045 0.3362 ILMN_1661335 SPTBN1 up 0 0.3487 11722689_a_at SPTBN1 spectrin, beta, non-erythrocytic 1 Plasma Membrane other up 0.0258 0.1701 11743839_a_at ST3GAL6 ST3 beta-galactoside alpha-2,3-sialyltransferase 6 Cytoplasm enzyme down 0.0064 -0.3927 ILMN_1781560 ST3GAL6 down 0.0006 -0.2037 11758670_s_at STK3 serine/threonine kinase 3 Cytoplasm kinase down 0.0212 -0.3041 ILMN_1666453 STK3 down 0.0196 -0.1212 11720598_x_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.0001 -0.3781 ILMN_1736054 SUB1 down 0.0116 -0.052 11758245_s_at SUB1 SUB1 homolog (S. cerevisiae) Nucleus transcription regulator down 0.0038 -0.1534 11732538_at TBX21 T-box 21 Nucleus transcription regulator up 0.0351 -0.0428 ILMN_1692714 TBX21 up 0.0237 0.1802 11744600_a_at TESPA1 thymocyte expressed, positive selection associated 1 Cytoplasm other up 0.0213 0.3513 ILMN_1690139 TESPA1 up 0.0405 0.1137 11748786_a_at TESPA1 thymocyte expressed, positive selection associated 1 Cytoplasm other up 0.047 0.2803 11736608_a_at TGM3 transglutaminase 3 (E polypeptide, protein-glutamine-gamma-glutamyltransferase)Cytoplasm enzyme down 0 -0.5278 ILMN_1786847 TGM3 down 0.0038 -0.2852 11724275_s_at TMEM158 transmembrane protein 158 (gene/pseudogene) Plasma Membrane other up 0.0003 0.6184 ILMN_1792455 TMEM158 up 0 0.3409 11720217_a_at TMEM176A transmembrane protein 176A unknown other down 0 -0.7344 ILMN_1791511 TMEM176A down 0 -0.3558 11719871_a_at TMEM176B transmembrane protein 176B unknown other down 0 -0.6169 ILMN_2085012 TMEM176B down 0.025 -0.0937 11724551_x_at TMEM55A transmembrane protein 55A unknown phosphatase down 0.0299 -0.1739 ILMN_1752117 TMEM55A down 0.0003 -0.2654 11743636_at TNFAIP6 tumor necrosis factor, alpha-induced protein 6 Extracellular Space other down 0.0014 -0.3587 ILMN_1785732 TNFAIP6 down 0.0484 -0.1568 11753764_s_at TNFRSF21 tumor necrosis factor receptor superfamily, member 21 Plasma Membrane transmembrane receptor up 0.0029 0.0814 ILMN_1699695 TNFRSF21 up 0.012 0.1761 11732111_a_at TNFRSF21 tumor necrosis factor receptor superfamily, member 21 Plasma Membrane transmembrane receptor up 0.0347 0.2834 11715469_s_at TXN thioredoxin Cytoplasm enzyme down 0.0166 -0.2913 ILMN_2038776 TXN down 0.0001 -0.3816 11753804_x_at TXN thioredoxin Cytoplasm enzyme down 0.0386 -0.2412 ILMN_1680314 TXN down 0.0038 -0.2935 11729844_at VNN1 vanin 1 Plasma Membrane enzyme down 0 -0.53 ILMN_1674574 VNN1 down 0.0001 -0.2965 11758233_s_at VNN1 vanin 1 Plasma Membrane enzyme down 0.0002 -0.449 11729843_s_at VNN1 vanin 1 Plasma Membrane enzyme down 0.003 -0.1727 11729842_at VNN1 vanin 1 Plasma Membrane enzyme down 0.0036 -0.473 11737877_a_at VNN3 vanin 3 Extracellular Space enzyme down 0.0215 -0.1749 ILMN_2387680 VNN3 down 0.0132 -0.1013 11751281_a_at VWCE von Willebrand factor C and EGF domains unknown other up 0 0.5145 ILMN_1760315 VWCE up 0.0091 0.3094 11756497_a_at VWCE von Willebrand factor C and EGF domains unknown other up 0.0008 0.4371 11745018_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.0002 -0.4238 ILMN_2283325 WLS down 0 -0.2068 11718761_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.0002 -0.261 ILMN_1671260 WLS down 0.0009 -0.295 11718760_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.0033 -0.2794 ILMN_1660549 WLS down 0.0021 -0.1308 Diabetes Page 98 of 111

11733513_a_at WLS wntless homolog (Drosophila) Cytoplasm other down 0.0054 -0.1927 11754534_a_at ZFYVE16 zinc finger, FYVE domain containing 16 Nucleus transporter down 0.0432 -0.1006 ILMN_1651769 ZFYVE16 down 0.0009 -0.1391 11739855_a_at ZFYVE16 zinc finger, FYVE domain containing 16 Nucleus transporter down 0.0461 -0.2457 11731062_s_at ZNF516 zinc finger protein 516 Nucleus other down 0.0233 -0.2375 ILMN_1699648 ZNF516 down 0.0424 -0.1265 Page 99 of 111 Diabetes

Differentially regulated genes in different time windows (previous sheets) were analyzed with DAVID pathway analysis tool. Pathways (BBID, BioCarta, KEGG, Panther, Reactome) with FDR <20% are reported.

Time window Category Term Count % PValue Genes List Total Pop Hits Pop Total Fold Enrichment Bonferroni Benjamini FDR Before seroconversion Up-regulation None Down-regulation KEGG_PATHWAY hsa03010:Ribosome 3 7.0 0.011911 RPL26, RPS27L, RSL24D1 11 87 5085 15.940438871473352 0.22247376694632304 0.22247376694632304 8.837193188014592 Up- or down-regulation KEGG_PATHWAY hsa05332:Graft-versus-host disease 3 2.5 0.021780 HLA-C, HLA-DPB1, KLRD1 31 39 5085 12.61786600496278 0.6368590174281159 0.6368590174281159 18.7904956211255 At seroconversion Up-regulation None Down-regulation None Up- or down-regulation None 6-18 m after seroconversion Up-regulation KEGG_PATHWAY hsa04610:Complement and coagulation cascades 6 3.5 0.000477 C3AR1, F5, SERPING1, C4BPA, C2, CFD 50 69 5085 8.843478260869565 0.0333120367559504 0.0333120367559504 0.4940452101509618 KEGG_PATHWAY hsa04630:Jak-STAT signaling pathway 6 3.5 0.015973 IL6ST, BCL2L1, IL5RA, MPL, STAT1, STAT2 50 155 5085 3.936774193548387 0.6812053271767694 0.43538094893704604 15.39023486199711 BIOCARTA h_ahspPathway:Hemoglobin's Chaperone 3 1.7 0.021425 GATA1, ALAS2, AHSP 29 12 1437 12.38793103448276 0.7273250855448131 0.7273250855448131 19.510891217091498 Down-regulation KEGG_PATHWAY hsa03010:Ribosome 11 3.0 0.000024 RPL17, MRPL13, RPL7, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPS27L, RPL39, RPS23 117 87 5085 5.495137046861185 0.002358785456323731 0.002358785456323731 0.0262084693268827 REACTOME_PATHWAY REACT_17015:Metabolism of proteins 16 4.3 0.000210 RPL17, RPL26, VBP1, RPS15A, RPL39, PIGK, PIGF, RPL7, RPS3A, RPL31, RPL9, PFDN5, RPS14, DPM1, RPS23, PIGA 85 217 3398 2.9475738682569803 0.007723908608463503 0.007723908608463503 0.18799444631180107 REACTOME_PATHWAY REACT_1762:3' -UTR-mediated translational regulation 10 2.7 0.001189 RPL17, RPL7, RPL31, RPS3A, RPL9, RPS14, RPL26, RPS15A, RPL39, RPS23 85 108 3398 3.701525054466231 0.04307210234870851 0.02177308478487905 1.0627647149508146 BIOCARTA h_DNAfragmentPathway:Apoptotic DNA fragmentation and tissue homeostasis 4 1.1 0.001414 HMGB1, HMGB2, CASP3, TOP2A 36 10 1437 15.966666666666665 0.10325429031049094 0.10325429031049094 1.4821971374079257 REACTOME_PATHWAY REACT_6167:Influenza Infection 11 3.0 0.004784 RPL17, RPL7, RPL31, RPS3A, RPL9, RPS14, RPL26, RPS15A, RPL39, RPS23, SNRPG 85 157 3398 2.8008992131884605 0.16259184247730163 0.057432641823066954 4.214801174774207 KEGG_PATHWAY hsa05012:Parkinson's disease 9 2.4 0.008457 NDUFA4, CASP3, COX7A2, NDUFS4, UBE2J1, COX7C, NDUFA1, UQCRQ, COX6C 117 128 5085 3.0558894230769234 0.5722704144259927 0.34598961355800517 8.99563992862732 KEGG_PATHWAY hsa05332:Graft-versus-host disease 5 1.4 0.011431 IL1B, HLA-C, HLA-DPB1, KLRD1, HLA-DQA1 117 39 5085 5.571992110453649 0.6832609849781787 0.31834097775964265 11.980046606635586 KEGG_PATHWAY hsa05010:Alzheimer's disease 10 2.7 0.011625 NDUFA4, CDK5R1, CASP3, COX7A2, NDUFS4, COX7C, IL1B, NDUFA1, UQCRQ, COX6C 117 163 5085 2.66635205285512 0.6894057821731636 0.25346814925782213 12.17123415869935 PANTHER_PATHWAY P00054:Toll receptor signaling pathway 5 1.4 0.015893 UBE2N, IRAK3, TLR10, LY96, IL18 45 64 2857 4.960069444444445 0.5722039721948462 0.5722039721948462 14.4704358609691 REACTOME_PATHWAY REACT_71:Gene Expression 16 4.3 0.022512 CCNT2, RPL17, SF3B14, RPL26, RPS15A, CCNC, RPL39, MED7, RPL7, RPS3A, RPL31, EEF1E1, RPL9, RPS14, RPS23, SNRPG 85 350 3398 1.8274957983193276 0.5693458943512653 0.18991209502686734 18.490098769235107 Up- or down-regulation KEGG_PATHWAY hsa03010:Ribosome 11 2.1 0.000339 RPL17, MRPL13, RPL7, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPS27L, RPL39, RPS23 160 87 5085 4.018318965517242 0.04014309717457021 0.04014309717457021 0.38852151137955815 REACTOME_PATHWAY REACT_17015:Metabolism of proteins 17 3.3 0.000835 RPL17, RPL26, VBP1, RPS15A, RPL39, PIGK, PIGF, RPL7, RPS3A, RPL31, RPS14, RPL9, PFDN5, FBXO6, DPM1, RPS23, PIGA 106 217 3398 2.5113468394052694 0.03607812147058542 0.03607812147058542 0.7782675812245343 KEGG_PATHWAY hsa05332:Graft-versus-host disease 7 1.4 0.001179 PRF1, IL1B, HLA-C, HLA-DPB1, KIR2DL3, KLRD1, HLA-DQA1 160 39 5085 5.7043269230769225 0.13305868727771508 0.06890316683908493 1.3474722004037987 REACTOME_PATHWAY REACT_1762:3' -UTR-mediated translational regulation 10 1.9 0.005567 RPL17, RPL7, RPL31, RPS3A, RPL9, RPS14, RPL26, RPS15A, RPL39, RPS23 106 108 3398 2.9682040531097136 0.21780620510377047 0.11558279364531276 5.0892589463632625 BIOCARTA h_DNAfragmentPathway:Apoptotic DNA fragmentation and tissue homeostasis 4 0.8 0.007061 HMGB1, HMGB2, CASP3, TOP2A 62 10 1437 9.270967741935483 0.5696728611609156 0.5696728611609156 7.800628370091667 REACTOME_PATHWAY REACT_6167:Influenza Infection 12 2.3 0.008318 RPL17, RPL7, RPL31, RPS3A, RPL9, RPS14, RPL26, RPS15A, RPL39, EIF2AK2, RPS23, SNRPG 106 157 3398 2.4501862756880186 0.3075566239884657 0.11530259165931711 7.517235659267641 BIOCARTA h_setPathway:Granzyme A mediated Apoptosis Pathway 4 0.8 0.015361 PRF1, HMGB2, NME1, GZMA 62 13 1437 7.13151364764268 0.8415255395876151 0.6019114917353368 16.258430133591297 KEGG_PATHWAY hsa05012:Parkinson's disease 10 1.9 0.018163 NDUFA4, CASP3, COX7A2, NDUFS4, SNCA, UBE2J1, COX7C, NDUFA1, UQCRQ, COX6C 160 128 5085 2.48291015625 0.8911673159208162 0.5225589242171247 19.001000606273422 1-2 y before T1D diagnosis Up-regulation KEGG_PATHWAY hsa05332:Graft-versus-host disease 5 2.6 0.000710 PRF1, HLA-A, HLA-C, KIR2DL3, HLA-DQA1 55 39 5085 11.853146853146853 0.0491441286700286 0.0491441286700286 0.7339629171002948 KEGG_PATHWAY hsa05330:Allograft rejection 4 2.1 0.006311 PRF1, HLA-A, HLA-C, HLA-DQA1 55 36 5085 10.272727272727272 0.36205853543030386 0.20128762087363627 6.359919579836282 REACTOME_PATHWAY REACT_6900:Signaling in Immune system 9 4.7 0.007180 SELP, LY96, HLA-A, HLA-C, TLR5, C2, KIR2DL3, PROS1, HLA-DQA1 36 286 3398 2.9702797202797204 0.14660866539693052 0.14660866539693052 5.483751259085179 KEGG_PATHWAY hsa04940:Type I diabetes mellitus 4 2.1 0.009703 PRF1, HLA-A, HLA-C, HLA-DQA1 55 42 5085 8.805194805194805 0.49957750452721283 0.20607598036813635 9.625192000303306 KEGG_PATHWAY hsa04612:Antigen processing and presentation 5 2.6 0.011238 HLA-A, HLA-C, KIR2DL3, HLA-DQA1, CTSL1 55 83 5085 5.569550930996714 0.5517429010090731 0.18175795071143241 11.067949108428854 KEGG_PATHWAY hsa05320:Autoimmune thyroid disease 4 2.1 0.016463 PRF1, HLA-A, HLA-C, HLA-DQA1 55 51 5085 7.251336898395722 0.6922937341169004 0.2099996785718673 15.82697632611334 Down-regulation KEGG_PATHWAY hsa03010:Ribosome 10 4.1 0.000002 RPL36A, MRPL13, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPS27L, RPL39, RPS23 69 87 5085 8.470764617691154 1.3926891741899983E-4 1.3926891741899983E-4 0.001888779612857494 REACTOME_PATHWAY REACT_1762:3' -UTR-mediated translational regulation 8 3.3 0.000519 RPL36A, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPL39, RPS23 47 108 3398 5.355397951142631 0.014931529781800346 0.014931529781800346 0.4370564793851117 REACTOME_PATHWAY REACT_6167:Influenza Infection 9 3.7 0.001011 RPL36A, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPL39, EIF2AK2, RPS23 47 157 3398 4.14446401951484 0.028908052942855478 0.014560023615266315 0.850435091844326 REACTOME_PATHWAY REACT_17015:Metabolism of proteins 10 4.1 0.002063 RPL36A, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPL39, PROS1, RPS23, PIGA 47 217 3398 3.3316991861947254 0.058127821091257026 0.019763981978222156 1.728478012649226 REACTOME_PATHWAY REACT_6900:Signaling in Immune system 11 4.5 0.004040 THBD, LY96, CD160, C1R, TREM1, KIR2DL3, CFD, KLRD1, PROS1, HLA-DOB, TLR8 47 286 3398 2.7806873977086743 0.1107653961088686 0.02892205934565395 3.360214824161334 KEGG_PATHWAY hsa04610:Complement and coagulation cascades 5 2.0 0.013179 THBD, C1R, SERPING1, CFD, PROS1 69 69 5085 5.3402646502835545 0.6447113972998186 0.4039390948064272 13.093345537224932 KEGG_PATHWAY hsa05332:Graft-versus-host disease 4 1.6 0.014827 IL1B, KIR2DL3, KLRD1, HLA-DOB 69 39 5085 7.558528428093646 0.6881337761669504 0.3218546618507234 14.616178480796915 Up- or down-regulation KEGG_PATHWAY hsa05332:Graft-versus-host disease 8 2.2 0.000009 PRF1, HLA-A, IL1B, HLA-C, KIR2DL3, KLRD1, HLA-DOB, HLA-DQA1 102 39 5085 10.226244343891402 8.763347136903077E-4 8.763347136903077E-4 0.009973899686266385 KEGG_PATHWAY hsa03010:Ribosome 10 2.7 0.000048 RPL36A, MRPL13, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPS27L, RPL39, RPS23 102 87 5085 5.730223123732252 0.004621398041873115 0.002313374872587093 0.052685448769618226 REACTOME_PATHWAY REACT_6900:Signaling in Immune system 17 4.6 0.000109 SELP, LY96, HLA-A, CD160, HLA-C, C1R, TLR5, TLR8, HLA-DQA1, THBD, C2, TREM1, KIR2DL3, CFD, KLRD1, PROS1, HLA-DOB 69 286 3398 2.9272321881017533 0.003919498994300441 0.003919498994300441 0.0972521239179236 KEGG_PATHWAY hsa04612:Antigen processing and presentation 8 2.2 0.001195 HSP90AA1, HLA-A, HLA-C, KIR2DL3, KLRD1, HLA-DOB, HLA-DQA1, CTSL1 102 83 5085 4.805102763997165 0.10947768112419298 0.03791169342501455 1.3104634729382503 KEGG_PATHWAY hsa04940:Type I diabetes mellitus 6 1.6 0.001329 PRF1, HLA-A, IL1B, HLA-C, HLA-DOB, HLA-DQA1 102 42 5085 7.121848739495798 0.12101431530674034 0.03173228690999352 1.4567613506575872 KEGG_PATHWAY hsa04610:Complement and coagulation cascades 7 1.9 0.002307 THBD, F13A1, C1R, SERPING1, C2, CFD, PROS1 102 69 5085 5.057544757033249 0.20068903633514557 0.0438122974007642 2.516298560273722 REACTOME_PATHWAY REACT_6167:Influenza Infection 10 2.7 0.003605 RPL36A, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPL39, EIF2AK2, RPS23, SNRPG 69 157 3398 3.1367118988276563 0.12191434173484905 0.06293775112581179 3.169801159385699 REACTOME_PATHWAY REACT_1762:3' -UTR-mediated translational regulation 8 2.2 0.005290 RPL36A, RPL31, RPS3A, RPL9, RPL26, RPS15A, RPL39, RPS23 69 108 3398 3.6478797638217926 0.17380965545705807 0.06166041404416367 4.620299718751064 KEGG_PATHWAY hsa05330:Allograft rejection 5 1.4 0.005303 PRF1, HLA-A, HLA-C, HLA-DOB, HLA-DQA1 102 36 5085 6.924019607843137 0.4029371497279124 0.08236491876128449 5.6986547849428355 KEGG_PATHWAY hsa05416:Viral myocarditis 6 1.6 0.012939 PRF1, CASP3, HLA-A, HLA-C, HLA-DOB, HLA-DQA1 102 71 5085 4.212924606462304 0.7172642032235284 0.16511659588377836 13.38685544191881 KEGG_PATHWAY hsa05320:Autoimmune thyroid disease 5 1.4 0.017946 PRF1, HLA-A, HLA-C, HLA-DOB, HLA-DQA1 102 51 5085 4.887543252595155 0.8273604140962536 0.19713495848391216 18.113980999981074 At T1D diagnosis Up-regulation KEGG_PATHWAY hsa05332:Graft-versus-host disease 4 5.3 0.000178 HLA-A, GZMB, HLA-C, KLRD1 16 39 5085 32.59615384615385 0.00656936599118662650.0065693659911866265 0.15982341419217283 KEGG_PATHWAY hsa05330:Allograft rejection 3 3.9 0.004829 HLA-A, GZMB, HLA-C 16 36 5085 26.484375 0.1639951480715809 0.08566699068204964 4.253779486817189 KEGG_PATHWAY hsa04650:Natural killer cell mediated cytotoxicity 4 5.3 0.006321 HLA-A, GZMB, HLA-C, KLRD1 16 133 5085 9.55827067669173 0.20913020940499805 0.07522731055378495 5.5347388774399935 KEGG_PATHWAY hsa04940:Type I diabetes mellitus 3 3.9 0.006533 HLA-A, GZMB, HLA-C 16 42 5085 22.700892857142858 0.2153508387894736 0.058828259336464184 5.715594827710701 KEGG_PATHWAY hsa05320:Autoimmune thyroid disease 3 3.9 0.009527 HLA-A, GZMB, HLA-C 16 51 5085 18.69485294117647 0.29827031086443256 0.06839036766491602 8.236807105368726 BBID 70.Signal_peptides_(MHC)_class_I_molecules 2 2.6 0.033238 HLA-A, HLA-C 5 3 358 47.733333333333334 0.155505256237635 0.155505256237635 13.671717604512557 KEGG_PATHWAY hsa04612:Antigen processing and presentation 3 3.9 0.024084 HLA-A, HLA-C, KLRD1 16 83 5085 11.487198795180722 0.594244787924646 0.13957962801134494 19.659676419505256 Down-regulation KEGG_PATHWAY hsa03010:Ribosome 8 5.7 0.000027 RPS26, RPL31, RPL9, RPL26, RPS15A, RSL24D1, RPL39, RPS23 54 87 5085 8.659003831417625 0.00161561312219282720.0016156131221928272 0.02736282228895659 KEGG_PATHWAY hsa05310:Asthma 5 3.5 0.000206 FCER1A, HLA-DRB4, MS4A2, HLA-DOB, HLA-DQA1 54 29 5085 16.235632183908045 0.012083377320830424 0.006060050768071035 0.20554677846102987 KEGG_PATHWAY hsa05330:Allograft rejection 5 3.5 0.000484 HLA-A, HLA-DRB4, HLA-C, HLA-DOB, HLA-DQA1 54 36 5085 13.078703703703702 0.028166621796008928 0.009478430731681642 0.4823989324087008 REACTOME_PATHWAY REACT_1762:3' -UTR-mediated translational regulation 7 5.0 0.000493 RPS26, RPL31, RPL9, RPL26, RPS15A, RPL39, RPS23 34 108 3398 6.477668845315903 0.009822468884439606 0.009822468884439606 0.374933300781799 KEGG_PATHWAY hsa05332:Graft-versus-host disease 5 3.5 0.000661 HLA-A, HLA-DRB4, HLA-C, HLA-DOB, HLA-DQA1 54 39 5085 12.072649572649572 0.038236665775605694 0.009699372912913229 0.6576854097044005 KEGG_PATHWAY hsa04940:Type I diabetes mellitus 5 3.5 0.000878 HLA-A, HLA-DRB4, HLA-C, HLA-DOB, HLA-DQA1 54 42 5085 11.21031746031746 0.05052814827524221 0.010316297085096293 0.8737181772780156 KEGG_PATHWAY hsa05320:Autoimmune thyroid disease 5 3.5 0.001830 HLA-A, HLA-DRB4, HLA-C, HLA-DOB, HLA-DQA1 54 51 5085 9.232026143790849 0.10243923175132108 0.017851154966082028 1.812545756735351 REACTOME_PATHWAY REACT_6167:Influenza Infection 7 5.0 0.003467 RPS26, RPL31, RPL9, RPL26, RPS15A, RPL39, RPS23 34 157 3398 4.455976020981641 0.06710886763950275 0.03413710478117171 2.6088943086632344 KEGG_PATHWAY hsa05416:Viral myocarditis 5 3.5 0.006104 HLA-A, HLA-DRB4, HLA-C, HLA-DOB, HLA-DQA1 54 71 5085 6.631455399061033 0.3031993324020674 0.050298909095333744 5.931129884792297 KEGG_PATHWAY hsa04612:Antigen processing and presentation 5 3.5 0.010534 HLA-A, HLA-DRB4, HLA-C, HLA-DOB, HLA-DQA1 54 83 5085 5.672690763052208 0.4646208880833005 0.07512577189371705 10.034580955474592 PANTHER_PATHWAY P00031:Inflammation mediated by chemokine and cytokine signaling pathway 6 4.3 0.016119 ALOX15, PTGS2, IL8, FPR1, RGS18, FPR2 16 304 2857 3.5242598684210527 0.3551709749214985 0.3551709749214985 12.596479058307143 REACTOME_PATHWAY REACT_17015:Metabolism of proteins 7 5.0 0.016362 RPS26, RPL31, RPL9, RPL26, RPS15A, RPL39, RPS23 34 217 3398 3.2239089184060723 0.2810433035033889 0.10415217341009664 11.799954695594261 KEGG_PATHWAY hsa05322:Systemic lupus erythematosus 5 3.5 0.019103 HIST1H2BD, FCGR1A, HLA-DRB4, HLA-DOB, HLA-DQA1 54 99 5085 4.755892255892256 0.6795391528943405 0.11877642224989715 17.519402590894863 BBID 70.Signal_peptides_(MHC)_class_I_molecules 2 1.4 0.024999 HLA-A, HLA-C 4 3 358 59.666666666666664 0.18334121560496808 0.18334121560496808 12.942213808850344 Up- or down-regulation KEGG_PATHWAY hsa05332:Graft-versus-host disease 7 3.4 0.000007 HLA-A, HLA-DRB4, GZMB, HLA-C, KLRD1, HLA-DOB, HLA-DQA1 65 39 5085 14.041420118343197 5.391027389022307E-4 5.391027389022307E-4 0.007710162856977565 KEGG_PATHWAY hsa05330:Allograft rejection 6 3.0 0.000075 HLA-A, HLA-DRB4, GZMB, HLA-C, HLA-DOB, HLA-DQA1 65 36 5085 13.03846153846154 0.005477315537125604 0.0027424181973473294 0.07850205255571785 KEGG_PATHWAY hsa03010:Ribosome 8 3.9 0.000095 RPS26, RPL31, RPL9, RPL26, RPS15A, RSL24D1, RPL39, RPS23 65 87 5085 7.193633952254642 0.00690080676996140950.002305580539685992 0.0989644835179826 KEGG_PATHWAY hsa04940:Type I diabetes mellitus 6 3.0 0.000160 HLA-A, HLA-DRB4, GZMB, HLA-C, HLA-DOB, HLA-DQA1 65 42 5085 11.175824175824177 0.011626037834316927 0.0029192677849732007 0.16706952388114704 KEGG_PATHWAY hsa05320:Autoimmune thyroid disease 6 3.0 0.000405 HLA-A, HLA-DRB4, GZMB, HLA-C, HLA-DOB, HLA-DQA1 65 51 5085 9.203619909502263 0.029169359751346824 0.005903156253096009 0.4223885560854179 KEGG_PATHWAY hsa05310:Asthma 5 2.5 0.000428 FCER1A, HLA-DRB4, MS4A2, HLA-DOB, HLA-DQA1 65 29 5085 13.488063660477454 0.030772541385217345 0.005195781526322607 0.44591737587548197 REACTOME_PATHWAY REACT_1762:3' -UTR-mediated translational regulation 7 3.4 0.001081 RPS26, RPL31, RPL9, RPL26, RPS15A, RPL39, RPS23 39 108 3398 5.647198480531814 0.024564776393927956 0.024564776393927956 0.8534707925900609 KEGG_PATHWAY hsa04612:Antigen processing and presentation 6 3.0 0.003681 HLA-A, HLA-DRB4, HLA-C, KLRD1, HLA-DOB, HLA-DQA1 65 83 5085 5.655236329935125 0.23599073063977527 0.037723668285800316 3.775688650332931 REACTOME_PATHWAY REACT_6167:Influenza Infection 7 3.4 0.007142 RPS26, RPL31, RPL9, RPL26, RPS15A, RPL39, RPS23 39 157 3398 3.884697043932713 0.15199327810547136 0.07912719559402315 5.523316056970895 KEGG_PATHWAY hsa05416:Viral myocarditis 5 2.5 0.011810 HLA-A, HLA-DRB4, HLA-C, HLA-DOB, HLA-DQA1 65 71 5085 5.509209100758397 0.5799135223098157 0.10274200299957748 11.662940779425057 Diabetes Page 100 of 111

Differentially regulated genes in different time windows (previous sheets) were analyzed through MSig database for enriched transcription factor binding sites on their promoters ( ±±±2 kb around the transcription start site). Motifs with p value < 0.05 are reported.

No match = Motif does not match any known transcription factor

Time window Enriched motif Motif sequence Transcription factor # Genes annotated to motif (K) # Overlapping input genes (k) k/K p value Genes Before seroconversion Up-regulated genes 244 6 0.0246 0.0039700 CREB5 SLC4A1 EPB42 BCL6 SNCA SMOX V$GATA1_02 NNNNNGATANKGNN GATA1 246 6 0.0244 0.0041300 CREB5 SLC4A1 EPB42 BCL6 EPB49 ADM V$LMO2COM_02 NMGATANSG LMO2 198 5 0.0253 0.0075900 CREB5 SLC4A1 EPB42 EPB49 ADM V$GATA_Q6 WGATARN GATA1 242 5 0.0207 0.0170000 CREB5 SLC4A1 EPB42 SNCA EPB49 V$GATA3_01 NNGATARNG GATA3 245 5 0.0204 0.0178000 CREB5 SLC4A1 EPB42 ADM C3AR1 V$GATA1_04 NNCWGATARNNNN GATA1 247 5 0.0202 0.0184000 PROK2 IFIT2 IFI44 IFIT3 HLA-C V$ISRE_01 CAGTTTCWCTTTYCC STAT1 & STAT2 267 5 0.0187 0.0247000 BCL6 NFIX TSHZ3 CCL8 ASGR2 V$CEBP_Q2_01 NTTRCNNAANNN CEBPA 40 2 0.0500 0.0253000 BCL6 SMOX V$AR_02 NNNGNRRGNACANNGTGTTCTNNNNNN AR 271 5 0.0185 0.0262000 PROK2 DYSF DSC2 CLC MMP9 V$BACH2_01 SRTGAGTCANC BACH2 188 4 0.0213 0.0291000 IFIT2 IFI44 IFIT3 NFIX STTTCRNTTT_V$IRF_Q6 STTTCRNTTT no match 295 5 0.0169 0.0358000 CREB5 SLC4A1 EPB42 EPB49 PHOSPHO1 GATAAGR_V$GATA_C GATAAGR no match Down-regulated genes STTTCRNTTT_V$IRF_Q6 STTTCRNTTT no match 188 3 0.0160 0.0194000 IFIT2 IFI44 EPSTI1 V$ISRE_01 CAGTTTCWCTTTYCC STAT1 & STAT2 247 3 0.0121 0.0392000 IFIT2 IFI44 EPSTI1 Up- or down-regulated genes V$LMO2COM_02 NMGATANSG LMO2 246 7 0.0285 0.0050900 CREB5 SLC4A1 EPB42 BCL6 EPB49 ADM HINT1 V$GATA1_02 NNNNNGATANKGNN GATA1 244 6 0.0246 0.0181000 CREB5 SLC4A1 EPB42 BCL6 SNCA SMOX V$ISRE_01 CAGTTTCWCTTTYCC STAT1 & STAT2 247 6 0.0243 0.0191000 IFIT2 EPSTI1 IFI44 IFIT3 PROK2 HLA-C STTTCRNTTT_V$IRF_Q6 STTTCRNTTT no match 188 5 0.0266 0.0224000 IFIT2 EPSTI1 IFI44 IFIT3 NFIX V$GATA_Q6 WGATARN GATA1 198 5 0.0253 0.0272000 CREB5 SLC4A1 EPB42 EPB49 ADM V$BACH2_01 SRTGAGTCANC BACH2 271 6 0.0221 0.0285000 PROK2 SCOC CLC DYSF DSC2 MMP9 V$AR_02 NNNGNRRGNACANNGTGTTCTNNNNNN AR 40 2 0.0500 0.0456000 BCL6 SMOX At seroconversion Up-regulation None Down-regulation None Up- or down-regulation YGACNNYACAR_UNKNOWN YGACNNYACAR no match 96 2 0.0208 0.0186000 SPATA20 C3AR1 6-18 m after seroconversion Up-regulation STTTCRNTTT_V$IRF_Q6 STTTCRNTTT no match 188 9 0.0479 0.0005460 DTX3L CXCL10 IFIT2 DDX58 EPSTI1 NFIX BCL2L1 IFI44 PGM5 V$IRF7_01 TNSGAAWNCGAAANTNNN IRF7 252 10 0.0397 0.0011600 DTX3L CXCL10 IFIT2 DDX58 EPSTI1 NFIX BCL6 MPL OASL PLEK2 V$STAT5A_02 TTCCNRGAANNNNNNTTCCNNGRR STAT5A 141 6 0.0426 0.0081200 BCL2L1 BCL6 TAL1 FOXP1 PDK4 LRRN3 V$ISRE_01 CAGTTTCWCTTTYCC STAT1 & STAT2 247 8 0.0324 0.0117000 DTX3L CXCL10 IFIT2 DDX58 EPSTI1 IFI44 HLA-C PML V$AR_02 NNNGNRRGNACANNGTGTTCTNNNNNN AR 40 3 0.0750 0.0131000 BCL6 SMOX SPTBN1 V$IRF_Q6 BNCRSTTTCANTTYY IRF1 242 7 0.0289 0.0308000 DTX3L CXCL10 IFIT2 IFI44 HLA-C MLL IFI35 CYTAGCAAY_UNKNOWN CYTAGCAAY no match 147 5 0.0340 0.0358000 NRGN PASK SEC14L1 AKAP13 SLC6A8 V$AR_03 NNNNNNRGNACRNNGTGTTCTNNNNNN AR 59 3 0.0508 0.0365000 BCL6 SMOX NRGN V$AR_01 GGTACANNRTGTTCT AR 157 5 0.0318 0.0454000 BCL6 SMOX SPTBN1 CDKN1A PMP22 Down-regulation None Up- or down-regulation None 1-2 y before T1D diagnosis Up-regulation V$AR_03 NNNNNNRGNACRNNGTGTTCTNNNNNN AR 59 4 0.0678 0.0084600 BCL6 SMOX NRGN RERE V$AR_02 NNNGNRRGNACANNGTGTTCTNNNNNN AR 40 3 0.0750 0.0170000 BCL6 SMOX SPTBN1 V$GATA_Q6 WGATARN GATA1 198 7 0.0354 0.0188000 CREB5 SLC4A1 KRT72 EPB42 EPB49 ADM TSPAN9 V$LMO2COM_02 NMGATANSG LMO2 246 8 0.0325 0.0195000 BCL6 CREB5 SLC4A1 KRT72 EPB42 EPB49 ADM SDPR V$ISRE_01 CAGTTTCWCTTTYCC STAT1 & STAT2 247 8 0.0324 0.0199000 SDPR CXCL10 IFIT2 IFI44 PROK2 HLA-C TNFRSF17 PML V$STAT3_01 NGNNATTTCCSGGAARTGNNN STAT3 22 2 0.0909 0.0357000 PROS1 SERPING1 STTTCRNTTT_V$IRF_Q6 STTTCRNTTT no match 188 6 0.0319 0.0438000 CXCL10 IFIT2 IFI44 NFIX PSIP1 PGM5 V$GATA3_01 NNGATARNG GATA3 242 7 0.0289 0.0478000 NRGN CREB5 SLC4A1 KRT72 EPB42 EPB49 SNCA V$HNF1_C DGTTAATKAWTNACCAM TCF1 243 7 0.0288 0.0487000 NFIX CLC PPP2R2B TNS1 SSH2 F13A1 TMCC2 V$GATA1_02 NNNNNGATANKGNN GATA1 244 7 0.0287 0.0496000 BCL6 SMOX CREB5 SLC4A1 KRT72 EPB42 SNCA Down-regulation V$AR_03 NNNNNNRGNACRNNGTGTTCTNNNNNN AR 59 4 0.0678 0.0209000 BCL6 KIAA1468 SMOX NRGN V$AR_02 NNNGNRRGNACANNGTGTTCTNNNNNN AR 40 3 0.0750 0.0342000 BCL6 KIAA1468 SMOX V$STAT_01 TTCCCGKAA no match 253 9 0.0356 0.0379000 BCL6 KIAA1468 SERPING1 IPO11 GK TAL1 HACE1 RPS15A IL18RAP Up- or down-regulation V$AR_03 NNNNNNRGNACRNNGTGTTCTNNNNNN AR 59 5 0.0847 0.0190000 BCL6 SMOX KIAA1468 RERE NRGN V$AR_02 NNNGNRRGNACANNGTGTTCTNNNNNN AR 40 4 0.1000 0.0202000 BCL6 SMOX KIAA1468 SPTBN1 At T1D diagnosis Up-regulation None Down-regulation None Up- or down-regulation None Page 101 of 111 Diabetes

Summary of the functional modules regulated in distinct phases of T1D development. Probes with FDR < 0.05 (Supplementary Table 4) were analyzed for the presence of functional modules. Upregulation or downregulation of the module is marked with red or blue, respectively, and the color intensity indicates the percentage of the regulated probes belonging to that module. Functional interpretation of the module map is shown as a color grid, as defined by Chaussabel et al. (Immunity 29:150-164, 2008).

Before seroconversion 1 2 3 4 5 6 7 8 9 10 11 M1 Upregulated probes (FDR < 0.01) M2 Downregulated probes (FDR < 0.01) M3 >20 16-20 11-15 6-10 0-5 % of differentially regulated probes belonging to module At seroconversion 1 2 3 4 5 6 7 8 9 10 11 Functional interpretation M1 1 2 3 4 5 6 7 8 9 10 11 M2 M1 M3 M2 M3 6-18 months after seroconversion 1 2 3 4 5 6 7 8 9 10 11 M1 M2 Plasma cells Neutrophils M3 Platelets Erythocytes B-cells T-cells 1-2 years before clinical T1D diagnosis Myeloid lineage Interferon 1 2 3 4 5 6 7 8 9 10 11 Ribosomal proteins Inflammation M1 Cytotoxic cells Undetermined M2 No module M3

At clinical T1D diagnosis 1 2 3 4 5 6 7 8 9 10 11 M1 M2 M3 Diabetes Page 102 of 111

Functional interpretation 1 2 3 4 5 6 7 8 9 10 11 Plasma cells Neutrophils M1 Platelets Erythocytes M2 B-cells T-cells M3 Myeloid lineage Interferon Ribosomal proteins Inflammation Cytotoxic cells Undetermined No module

Up: M2.2: p-value: 0.000940, intersect: 10.5% M2.3: p-value: 0.000000, intersect: 26.3% M3.1: p-value: 0.000000, intersect: 26.3%

Down: M2.1: p-value: 0.000911, intersect 20.0% M3.1: p-value: 0.000000, intersect: 40%

Upregulated: Downregulated:

M2.2 M2.3 M3.1 M2.1 M3.1 MMP9 SELENBP1 IFITM3 GLT25D2 IFI44 CEACAM1 TNS1 MX1 KLRD1 IFIT2 ANXA3 SLC6A8 OAS1 KLRF1 IFI44L HBD GMPR IFI44 GNLY OAS3 EPB49 IFIT2 SAMD9L SLC4A1 IFI44L EPSTI1 SNCA OAS3 RSAD2 TRIM58 IFIT3 HERC5 FAM46C RSAD2 IGF2BP2 HERC5 Page 103 of 111 Diabetes

At seroconversion 1 2 3 4 5 6 7 8 9 10 11 M1 Upregulated probes (FDR < 0.01) M2 Downregulated probes (FDR < 0.01) M3 >20 16-20 11-15 6-10 0-5 % of differentially regulated probes belonging to module

Up: M2.2: p-value: 0.000000, intersect: 57.1% Down:

Upregulated: Downregulated: BPI DEFA4 CEACAM8 LCN2 Diabetes Page 104 of 111

6-18 months after seroconversion 1 2 3 4 5 6 7 8 9 10 11 M1 Upregulated probes (FDR < 0.01) M2 Downregulated probes (FDR < 0.01) M3 >20 16-20 11-15 6-10 0-5 % of differentially regulated probes belonging to module

Up: M2.2: p-value: 0.000050, intersect 8.1% M2.3: p-value: 0.000000, intersect: 19.8% M3.1: p-value: 0.000000, intersect: 34.9% Down: M1.7: p-value: 0.001018, intersect: 6.8% M2.2: p-value: 0.000113, intersect: 6.1% M3.1: p-value: 0.000241, intersect 9.1%

Upregulated: Downregulated:

M2.2 M2.3 M3.1 M1.7 M2.2 M3.1 MMP9 ADIPOR1 IFITM3 HLA-C S100P IFITM3 MYL4 SELENBP1 SERPING1 RPS14 MMP9 MX1 CEACAM1 TNS1 LY6E RPL7 CEACAM1 CHMP5 HBD SLC6A8 MX1 RPS3A ANXA3 OAS1 TCN1 GMPR DTX3L RPS23 CAMP IFI44 CSDA MYL4 STAT2 RPS15A CEACAM8 IFIT2 LCN2 MPP1 IFI6 RPL31 ARG1 IFI44L EPB49 IFI35 RPL17 LCN2 OAS3 SLC4A1 OAS1 RPL39 EPSTI1 CA1 IFI44 RSAD2 KLF1 CXCL10 TNFSF10 SNCA LAP3 HERC5 TRIM58 IFIT2 FAM46C PARP14 BCL2L1 IFI44L IGF2BP2 OAS3 TSPAN5 GBP1 OASL STAT1 PRIC285 PML EIF2AK2 EPSTI1 ANKRD22 DDX58 RSAD2 FBXO6 ZNFX1 PARP9 HERC5 Page 105 of 111 Diabetes

1-2 years before clinical T1D diagnosis 1 2 3 4 5 6 7 8 9 10 11 M1 Upregulated probes (FDR < 0.01) M2 Downregulated probes (FDR < 0.01) M3 >20 16-20 11-15 6-10 0-5 % of differentially regulated probes belonging to module

Up: M1.2: p-value: 0.000000, intersect: 17.1% M2.2: p-value: 0.000335, intersect: 7.3% M2.3: p-value: 0.000002, intersect: 14.6% M3.1: p-value: 0.000000, intersect: 20.7% Down: M2.1: p-value: 0.000410, intersect: 8.8% M2.2: p-value: 0.000002, intersect: 8.8% M3.1: p-value: 0.000000, intersect: 14.7%

Upregulated: Downregulated:

M1.2 M2.2 M2.3 M3.1 M2.1 M2.2 M3.1 F13A1 MYL4 SELENBP1 IFITM3 GZMA S100P IFITM3 SH3BGRL2 CEACAM1 TNS1 SERPING1 GLT25D2 MMP9 SERPING1 NRGN ANXA3 SLC6A8 LY6E CST7 CEACAM1 MX1 MMD HBD GSPT1 MX1 GZMH ANXA3 IFI6 PROS1 CSDA GMPR IFI44 LAIR2 HBD OAS1 TSPAN33 LCN2 MYL4 CXCL10 PTGDR CAMP IFI44 SDPR EPB49 IFIT2 CD160 DEFA4 IFIT2 CMTM5 SLC4A1 PARP14 KLRD1 CEACAM8 TRIM22 CA2 SNCA IFI44L GNLY LCN2 IFI44L CTTN TMOD1 OAS3 OAS3 FRMD3 IGF2BP2 OASL IFIH1 C5orf4 TSPAN5 PML EIF2AK2 ACRBP EIF2AK2 EPSTI1 SELP ADAR RSAD2 RSAD2 HERC5 PARP9 HERC5 Diabetes Page 106 of 111

At clinical T1D diagnosis 1 2 3 4 5 6 7 8 9 10 11 M1 Upregulated probes (FDR < 0.01) M2 Downregulated probes (FDR < 0.01) M3 >20 16-20 11-15 6-10 0-5 % of differentially regulated probes belonging to module

Up: M2.1: p-value: 0.000000, intersect: 35.7% M3.1: p-value: 0.000001, intersect: 28.6% Down: M1.7: p-value: 0.002621, intersect: 10.2% M2.2: p-value: 0.000000, intersect: 16.3% M3.1: p-value: 0.000001, intersect: 20.4% M3.3: p-value: 0.001458, intersect: 20.0%

Upregulated: Downregulated:

M2.1 M3.1 M1.7 M2.2 M3.1 M3.3 GPR56 LY6E HLA-C SLPI IFITM3 LAMP2 SPON2 OAS1 RPS23 S100P MX1 CAPZA2 GLT25D2 IFI44 RPS15A MMP9 OAS1 FCHO2 CLIC3 LAP3 RPL31 CEACAM1 IFI44 S100A12 GZMB IFI44L RPL39 HBD IFIT2 DSC2 GZMH OAS3 CAMP IFI44L SLC11A1 TBX21 OASL MS4A3 OAS3 LY96 KLRD1 RSAD2 LCN2 IFIT3 VNN1 KLRF1 RSAD2 HAL GNLY HERC5 SNX10 Page 107 of 111 Diabetes

Differentially expressed genes in seroconverted cases who later progressed to T1D (FDR < 0.05) showing concordant changes in Affymetrix and Illumina arrays before seroconversion

Differentially expressed genes in seroconverted cases who later progressed to T1D (FDR < 0.05) showing concordant changes in Affymetrix and Illumina arrays at seroconversion

Differentially expressed genes in seroconverted cases who later progressed to T1D (FDR < 0.05) showing concordant changes in Affymetrix and Illumina arrays after seroconversion

AFFYMETRIX ILLUMINA Affymetrix ID Gene Symbol (IPA) Gene name (IPA) Location (IPA) Type (IPA) Drug (IPA) Change probeset FDR log(mean(sick/ctrl))-log(mean(healthy/ctrl)) Illumina ID Gene Symbol (IPA) Change probe FDR log(mean(sick/ctrl))-log(mean(healthy/ctrl)) 11729337_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase down 0.04 -0.6762 ILMN_1701603 ALPL down 0.0006 -0.812833751 11729336_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase down 0.0249 -0.7858 11748031_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase down 0.015 -0.8333 11750919_a_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase down 0.0293 -0.8473 11748032_x_at ALPL alkaline phosphatase, liver/bone/kidney Plasma Membrane phosphatase down 0.0095 -0.9128 11726243_a_at ANKDD1A ankyrin repeat and death domain containing 1A unknown other up 0.0135 1.0934 ILMN_1813139 ANKDD1A up 0.0161 0.609986502 11743264_x_at C14orf2 chromosome 14 open reading frame 2 Cytoplasm other up 0.016 1.1452 ILMN_1652722 C14orf2 up 0.0072 0.701566922 11755220_a_at C17orf97 chromosome 17 open reading frame 97 unknown other up 0.0378 0.2943 ILMN_1707137 C17orf97 up 0.0155 0.183675485 11746124_x_at C21orf7 chromosome 21 open reading frame 7 unknown other up 0.0469 0.8274 ILMN_1699071 C21orf7 up 0.0444 0.544010992 11723949_a_at C4BPA complement component 4 binding protein, alpha Extracellular Space other up 0.0033 1.0904 ILMN_1810752 C4BPA up 0.0442 0.284839222 11744719_x_at C4BPA complement component 4 binding protein, alpha Extracellular Space other up 0.0018 1.0672 11731727_x_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase down 0.0397 -0.9497 ILMN_1722158 CASP5 down 0.0028 -1.000948382 11731726_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase down 0.0104 -1.4427 11753343_a_at CASP5 caspase 5, apoptosis-related cysteine peptidase Cytoplasm peptidase down 0.0036 -1.6228 11728027_x_at CCDC58 coiled-coil domain containing 58 Cytoplasm other up 0.0494 0.9375 ILMN_1686920 CCDC58 up 0.0353 0.561243175 11763718_x_at CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2) Nucleus other down 0.0068 -1.4651 ILMN_1718565 CDKN1C down 0.0185 -0.65307388 11763717_a_at CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2) Nucleus other down 0.0053 -1.4934 11760081_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary Plasma Membrane other down 0.0491 -0.8168 ILMN_1664330 CEACAM1 down 0.016 -0.771559831 11751217_x_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary Plasma Membrane other down 0.049 -0.8217 ILMN_1716815 CEACAM1 down 0.0135 -0.550615206 11751094_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary Plasma Membrane other down 0.0329 -0.8561 11756058_a_at CEACAM1 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary Plasma Membrane other down 0.0367 -0.8684 11733496_x_at COMMD6 COMM domain containing 6 unknown other up 0 1.5296 ILMN_1777378 COMMD6 up 0.0095 0.689331314 11756875_x_at COMMD6 COMM domain containing 6 unknown other up 0.002 1.4228 11733495_a_at COMMD6 COMM domain containing 6 unknown other up 0.0017 1.3865 11753841_x_at COMMD6 COMM domain containing 6 unknown other up 0.0021 1.3614 11754444_x_at COX6C cytochrome c oxidase subunit VIc Cytoplasm enzyme up 0.0198 1.0586 ILMN_1654151 COX6C up 0.0042 0.892073052 11717634_a_at COX6C cytochrome c oxidase subunit VIc Cytoplasm enzyme up 0.0238 1.0391 11715349_a_at COX7C cytochrome c oxidase subunit VIIc Cytoplasm enzyme up 0.0421 0.9594 ILMN_1798189 COX7C up 0 1.033328024 11735847_a_at CPA5 carboxypeptidase A5 Extracellular Space peptidase up 0.0354 0.7225 ILMN_1791530 CPA5 up 0.002 0.738199943 11720411_s_at CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide 1 Cytoplasm enzyme up 0.0423 0.8024 ILMN_1693338 CYP1B1 up 0.0019 0.728245821 11716579_a_at CYSTM1 cysteine-rich transmembrane module containing 1 unknown other down 0.0438 -0.8831 ILMN_1761566 CYSTM1 down 0.0162 -0.647531103 11719223_a_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other down 0.0494 -0.7689 ILMN_1810420 DYSF down 0.0135 -0.59988747 11747936_a_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other down 0.0351 -0.8123 11745836_x_at DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Plasma Membrane other down 0.0289 -0.8737 11720023_a_at FAM118A family with sequence similarity 118, member A unknown other up 0.0158 1.0337 ILMN_1809147 FAM118A up 0.014 0.77288646 11746669_a_at FAM118A family with sequence similarity 118, member A unknown other up 0.0232 0.9481 11744141_x_at FOLR3 folate receptor 3 (gamma) Extracellular Space other down 0.018 -0.7045 ILMN_1730454 FOLR3 down 0.0294 -0.322860286 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other down 0 -2.3074 ILMN_1721113 HLA-C down 0.0008 -0.719382468 11719491_a_at IFI35 interferon-induced protein 35 Nucleus other down 0.0403 -0.8943 ILMN_1745374 IFI35 down 0.0019 -0.924725013 11719492_s_at IFI35 interferon-induced protein 35 Nucleus other down 0.0371 -0.9002 11760254_at IFI44 interferon-induced protein 44 Cytoplasm other down 0.0452 -0.9382 ILMN_1760062 IFI44 down 0.012 -0.564809851 11760252_at IFI44 interferon-induced protein 44 Cytoplasm other down 0.0452 -1.0119 11723236_at IFI44L interferon-induced protein 44-like unknown other down 0.0194 -1.025 ILMN_1723912 IFI44L down 0.0005 -0.860535815 11715239_x_at IFITM3 interferon induced transmembrane protein 3 Plasma Membrane other down 0.0068 -0.9868 ILMN_1805750 IFITM3 down 0 -1.175287816 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator down 0 -1.4472 ILMN_1670576 IRF5 down 0.0007 -0.832825427 11732455_at KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 Plasma Membrane ion channel down 0.0497 -0.8898 ILMN_1675756 KCNJ15 down 0.0441 -0.537906012 11732454_at KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 Plasma Membrane ion channel down 0.027 -0.9619 11753534_a_at KLRD1 killer cell lectin-like receptor subfamily D, member 1 Plasma Membrane transmembrane receptor up 0.0383 0.9022 ILMN_1799134 KLRD1 up 0.0331 0.395590963 11730656_a_at LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), Extracellular Space other up 0.0062 1.1143 ILMN_1786303 LILRA3 up 0 1.277207162 11753808_s_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other up 0.0164 1.0805 ILMN_1719032 LSM3 up 0.0144 0.772606245 11716311_x_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other up 0.0197 1.0427 11753809_x_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other up 0.0234 1.0001 11757092_s_at LSM3 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) Nucleus other up 0.0252 0.9733 11728507_at LY96 lymphocyte antigen 96 Plasma Membrane other up 0.0253 0.9173 ILMN_1724533 LY96 up 0.0032 0.607233313 11721262_at MRPL50 mitochondrial ribosomal protein L50 Cytoplasm other up 0.0237 1.0084 ILMN_1664833 MRPL50 up 0.0344 0.498990089 11743645_s_at MXRA7 matrix-remodelling associated 7 unknown other up 0 1.5506 ILMN_1743836 MXRA7 up 0.0423 0.470044015 11758622_s_at MXRA7 matrix-remodelling associated 7 unknown other up 0.0029 1.2438 11718168_a_at MYOF myoferlin Nucleus other down 0.0236 -1.1363 ILMN_1810289 MYOF down 0.0005 -0.904489921 11725136_a_at MYOM2 myomesin (M-protein) 2, 165kDa Cytoplasm other down 0 -1.163 ILMN_1716733 MYOM2 down 0 -1.098986158 11736283_s_at NKX3-1 NK3 homeobox 1 Nucleus transcription regulator up 0.0163 0.6571 ILMN_1667162 NKX3-1 up 0.0486 0.648038094 11719588_a_at OAS1 2'-5'-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme down 0.0442 -0.8342 ILMN_1658247 OAS1 down 0.0354 -0.201667024 11740891_a_at OAS1 2'-5'-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme down 0.0216 -0.8962 ILMN_1675640 OAS1 down 0.0223 -0.650149298 11724255_a_at OAS1 2'-5'-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme down 0.0098 -0.9626 11723699_s_at OAS3 2'-5'-oligoadenylate synthetase 3, 100kDa Cytoplasm enzyme down 0.0497 -0.7941 ILMN_1745397 OAS3 down 0.0077 -0.827044702 11723698_a_at OAS3 2'-5'-oligoadenylate synthetase 3, 100kDa Cytoplasm enzyme down 0.0287 -0.8758 11744905_x_at ORM1 orosomucoid 1 Extracellular Space other up 0.0192 0.9178 ILMN_1696584 ORM1 up 0.01 0.570059988 11744904_a_at ORM1 orosomucoid 1 Extracellular Space other up 0.02 0.8772 11754065_x_at ORM1 orosomucoid 1 Extracellular Space other up 0.0375 0.7416 11758794_x_at ORM1 orosomucoid 1 Extracellular Space other up 0.0469 0.7004 11721650_at PI3 peptidase inhibitor 3, skin-derived Extracellular Space other down 0.0153 -0.8723 ILMN_1693192 PI3 down 0.0086 -0.605682453 11743087_at PPBP pro-platelet basic protein (chemokine (C-X-C motif) ligand 7) Extracellular Space cytokine up 0.0439 0.862 ILMN_1767281 PPBP up 0.0054 0.841595298 11720134_s_at PROS1 protein S (alpha) Extracellular Space other up 0.0039 1.2645 ILMN_1671928 PROS1 up 0.0405 0.452211686 11755743_a_at RNASE2 ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin) Cytoplasm enzyme up 0.0419 0.6864 ILMN_1730628 RNASE2 up 0 1.186414137 11757329_s_at RPL26 ribosomal protein L26 Cytoplasm other up 0.0015 1.3468 ILMN_1731546 RPL26 up 0.0139 0.77002714 11757421_x_at RPL31 ribosomal protein L31 Nucleus other up 0.0422 0.9548 ILMN_1754195 RPL31 up 0 1.022841933 11757027_x_at RPL31 ribosomal protein L31 Nucleus other up 0.0419 0.9342 11729387_x_at RPL31 ribosomal protein L31 Nucleus other up 0.0422 0.9274 11729386_s_at RPL31 ribosomal protein L31 Nucleus other up 0.0387 0.9228 11763301_x_at RPL39 ribosomal protein L39 Cytoplasm other up 0.0282 1.021 ILMN_1737015 RPL39 up 0.0007 0.937163718 11758357_x_at RPL9 ribosomal protein L9 Cytoplasm other up 0.038 0.9483 ILMN_1750507 RPL9 up 0.0053 0.758497945 11723251_at RPS15A ribosomal protein S15a Cytoplasm other up 0.0151 1.1275 ILMN_1787949 RPS15A up 0.009 0.786161359 11744350_a_at RPS27L ribosomal protein S27-like Nucleus other up 0.0175 1.0779 ILMN_1712678 RPS27L up 0.0033 0.794995217 11739217_a_at RSAD2 radical S-adenosyl methionine domain containing 2 Cytoplasm enzyme down 0.0107 -1.0369 ILMN_1657871 RSAD2 down 0.0018 -0.811828815 11751845_x_at SERPING1 serpin peptidase inhibitor, clade G (C1 inhibitor), member 1 Extracellular Space other down 0.0069 -0.8911 ILMN_1670305 SERPING1 down 0.0066 -0.893581872 11715368_a_at SERPING1 serpin peptidase inhibitor, clade G (C1 inhibitor), member 1 Extracellular Space other down 0.0064 -0.942 11736145_a_at SPATA20 spermatogenesis associated 20 unknown other up 0.0025 1.4714 ILMN_1687247 SPATA20 up 0 1.184471465 11720217_a_at TMEM176A transmembrane protein 176A unknown other down 0 -1.6119 ILMN_1791511 TMEM176A down 0.0011 -0.957156935 11751841_a_at TNFRSF17 tumor necrosis factor receptor superfamily, member 17 Plasma Membrane other up 0.0499 0.8525 ILMN_1768016 TNFRSF17 up 0.0096 0.690887521 11733901_a_at UQCRQ ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5kDa Cytoplasm enzyme up 0.0235 1.0649 ILMN_1666471 UQCRQ up 0.0019 0.788222833 Diabetes Page 110 of 111

cis eQTLs (FDR < 0.05) among the differentially regulated genes (FDR < 0.05), their validation in Westra et al. 2013, and information of association to autoimmune diseases in genome wide association studies Information from T1DBase (www.t1dbase.org) Information from Ricaño-Ponce and Wijmenga Annu Rev Genomics Hum Genet. 2013, in press. Key: Note: HLA excluded HA Highly associated: -log(p) >= 9 A Associated: 7 <= -log(p) < 9 Key: L Weak association: 3 <= -log(p) < 7 A/HA Genome wide signifigance: -log(p) >7 NA No association: -log(p) < 3 Matching to identified cis eQTL SNPs Proxy (r2 > 0.8) summary GWAS Immunochip GWAS Immunochip Probe ID Gene Symbol (IPA) Gene name (IPA) Location (IPA) Type (IPA) Drug (IPA) SNP ID (rs number) SNP location Gene location Distance from gene FDR (cis eQTL) cis eQTL confirmed MS CEL T1D T1D AITD CEL RA MS CEL T1D T1D AITD CEL RA AS CeD CD IgA MS PBC PS RA SLE T1D UC 11724410_x_at MARCH2 membrane-associated ring finger (C3HC4) 2, E3 ubiquitin protein ligase Cytoplasm enzyme rs17160491 chr19:8418940 chr19:8384187-8409897 9043 0.00021 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11724410_x_at MARCH2 membrane-associated ring finger (C3HC4) 2, E3 ubiquitin protein ligase Cytoplasm enzyme rs2967605 chr19:8375738 chr19:8384187-8409897 8449 0.01252 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11739641_a_at AFAP1 actin filament associated protein 1 Cytoplasm other rs10023670 chr4:7745372 chr4:7811340-7992553 65968 0.00393 NA NA NA NA NA NA NA NA NA NA 11739641_a_at AFAP1 actin filament associated protein 1 Cytoplasm other rs6845903 chr4:7751612 chr4:7811340-7992553 59728 0.01600 NA NA NA NA NA NA NA NA 11727638_a_at AHI1 Abelson helper integration site 1 Cytoplasm other rs11154801 chr6:135781048 chr6:135750615-135860596 0 0.00000 X HA NA NA NA NA NA NA HA NA NA NA NA NA NA A/HA 11727638_a_at AHI1 Abelson helper integration site 1 Cytoplasm other rs2179781 chr6:135761193 chr6:135750615-135860596 0 0.00036 X NA L L NA HA NA NA NA L L NA 11727638_a_at AHI1 Abelson helper integration site 1 Cytoplasm other rs6934889 chr6:135992373 chr6:135750615-135860596 131777 0.00073 NA L NA NA NA L NA NA L NA NA NA 11727638_a_at AHI1 Abelson helper integration site 1 Cytoplasm other rs13208164 chr6:135762978 chr6:135750615-135860596 0 0.00906 X L NA NA NA NA NA L NA NA NA NA NA 11727638_a_at AHI1 Abelson helper integration site 1 Cytoplasm other rs9402715 chr6:135901390 chr6:135750615-135860596 40794 0.02527 A NA NA NA L NA NA HA NA NA NA L NA NA 11727638_a_at AHI1 Abelson helper integration site 1 Cytoplasm other rs12210389 chr6:136024808 chr6:135750615-135860596 164212 0.03814 L NA NA NA NA NA NA L NA NA NA NA NA NA 11734503_x_at ALOX15 arachidonate 15-lipoxygenase Cytoplasm enzyme rs3786047 chr17:4561847 chr17:4480970-4491709 70138 0.01163 NA NA NA NA NA NA NA NA NA NA NA NA 11726243_a_at ANKDD1A ankyrin repeat and death domain containing 1A unknown other rs10162671 chr15:62817009 chr15:62991154-63038092 174145 0.00008 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11726243_a_at ANKDD1A ankyrin repeat and death domain containing 1A unknown other rs11631564 chr15:62760664 chr15:62991154-63038092 230490 0.00129 NA NA NA Excluded NA NA NA NA NA NA NA NA NA 11748557_a_at APIP APAF1 interacting protein Cytoplasm enzyme rs7115749 chr11:34817159 chr11:34860419-34894515 43260 0.00078 NA NA NA NA NA NA NA NA NA NA NA 11748557_a_at APIP APAF1 interacting protein Cytoplasm enzyme rs87603 chr11:35007815 chr11:34860419-34894515 113300 0.04473 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11731404_at ATP6V1G1 ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G1 Cytoplasm transporter rs10125974 chr9:116516444 chr9:116389815-116400972 115472 0.02457 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11736058_s_at C10orf32 chromosome 10 open reading frame 32 unknown other rs4919691 chr10:104614465 chr10:104603957-104614708 0 0.00482 NA NA NA NA NA NA NA NA NA NA 11736058_s_at C10orf32 chromosome 10 open reading frame 32 unknown other rs3736922 chr10:104840622 chr10:104603957-104614708 225914 0.02372 NA NA NA NA NA NA NA NA NA NA 11726485_at CPED1 cadherin-like and PC-esterase domain containing 1 Cytoplasm other rs10261386 chr7:120499091 chr7:120415987-120724733 0 0.00520 X NA NA NA NA NA NA NA NA NA NA NA 11726081_a_at CCNT2 cyclin T2 Nucleus transcription regulator rs6751833 chr2:135254368 chr2:135392863-135431054 138495 0.04982 NA NA NA NA NA NA NA NA NA NA 11741519_s_at CD14 CD14 molecule Plasma Membrane transmembrane receptor rs2569192 chr5:139995392 chr5:139991497-139993470 1922 0.03145 X NA Excluded NA NA NA NA NA NA NA NA NA NA 11750359_x_at CD68 CD68 molecule Plasma Membrane other rs4968212 chr17:7408940 chr17:7423529-7426152 14589 0.00006 NA NA NA NA NA NA NA NA NA NA NA 11750359_x_at CD68 CD68 molecule Plasma Membrane other rs62059839 chr17:7473740 chr17:7423529-7426152 47588 0.00295 NA NA NA NA NA NA NA 11750359_x_at CD68 CD68 molecule Plasma Membrane other rs3853818 chr17:7287026 chr17:7423529-7426152 136503 0.01017 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11723679_s_at CD69 CD69 molecule Plasma Membrane transmembrane receptor rs77209447 chr12:9648619 chr12:9798431-9804764 149812 0.04885 NA NA NA NA 11725576_s_at CDC14A CDC14 cell division cycle 14 homolog A (S. cerevisiae) Nucleus phosphatase rs7516666 chr1:100584447 chr1:100590611-100723513 6164 0.04112 X NA NA NA NA NA NA NA NA NA NA NA NA 11732058_a_at CDC7 cell division cycle 7 homolog (S. cerevisiae) Nucleus kinase rs12125947 chr1:91763075 chr1:91738992-91763908 0 0.02437 X NA NA NA NA NA NA NA NA NA L NA NA 11722022_s_at CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35) Nucleus kinase rs735555 chr17:27841563 chr17:27838218-27842383 0 0.00038 X NA NA NA NA NA NA NA NA NA NA NA 11725980_at CFD complement factor D (adipsin) Extracellular Space peptidase rs13090 chr19:819115 chr19:810665-814608 4507 0.03192 L NA NA NA NA NA L NA NA NA NA NA 11725980_at CFD complement factor D (adipsin) Extracellular Space peptidase rs2930894 chr19:832161 chr19:810665-814608 17553 0.04727 X NA NA NA NA L NA NA NA NA NA NA 11730536_at CHST13 carbohydrate (chondroitin 4) sulfotransferase 13 Cytoplasm enzyme rs777486 chr3:127716600 chr3:127725866-127744823 9266 0.00221 NA NA NA NA NA NA NA NA 11730536_at CHST13 carbohydrate (chondroitin 4) sulfotransferase 13 Cytoplasm enzyme rs17743103 chr3:127771099 chr3:127725866-127744823 26276 0.00885 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11721831_at CHURC1 churchill domain containing 1 Nucleus transcription regulator rs4899160 chr14:64550965 chr14:64450893-64471666 79299 0.01872 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11716092_x_at CKS1B CDC28 protein kinase regulatory subunit 1B unknown kinase rs45444697 chr1:153301256 chr1:153213742-153218348 82908 0.04474 NA NA NA NA NA NA 11753241_s_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other rs7302029 chr12:10000915 chr12:10015275-10029459 14360 0.00000 NA NA NA NA NA NA NA NA NA NA 11753241_s_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other rs7957464 chr12:9995556 chr12:10015275-10029459 19719 0.00000 X NA NA NA NA NA NA NA NA NA NA NA NA 11753241_s_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other rs28588142 chr12:9988876 chr12:10015275-10029459 26399 0.00000 NA NA NA NA NA NA 11753241_s_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other rs73048817 chr12:9951392 chr12:10015275-10029459 63883 0.00513 NA NA NA NA NA NA 11753241_s_at CLEC12A C-type lectin domain family 12, member A Plasma Membrane other rs7957596 chr12:10003536 chr12:10015275-10029459 11739 0.02309 NA NA NA NA NA NA NA NA NA NA 11732904_a_at CLEC1B C-type lectin domain family 1, member B Plasma Membrane transmembrane receptor rs7302029 chr12:10000915 chr12:10036931-10043166 36016 0.00000 NA NA NA NA NA NA NA NA NA NA 11732904_a_at CLEC1B C-type lectin domain family 1, member B Plasma Membrane transmembrane receptor rs7957464 chr12:9995556 chr12:10036931-10043166 41375 0.00222 NA NA NA NA NA NA NA NA NA NA NA NA 11732904_a_at CLEC1B C-type lectin domain family 1, member B Plasma Membrane transmembrane receptor rs28588142 chr12:9988876 chr12:10036931-10043166 48055 0.00473 NA NA NA NA NA NA 11726437_a_at CMTM8 CKLF-like MARVEL transmembrane domain containing 8 Extracellular Space cytokine rs17029181 chr3:32321120 chr3:32255175-32386815 0 0.04081 X NA NA NA NA NA L NA NA NA NA NA NA L NA 11726437_a_at CMTM8 CKLF-like MARVEL transmembrane domain containing 8 Extracellular Space cytokine rs4132830 chr3:32290387 chr3:32255175-32386815 0 0.04969 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11734956_a_at CNTNAP2 contactin associated protein-like 2 Plasma Membrane other rs2222764 chr7:146823608 chr7:145444386-147749019 0 0.04982 NA NA NA NA NA NA NA NA NA NA NA NA 11734956_a_at CNTNAP2 contactin associated protein-like 2 Plasma Membrane other rs10225019 chr7:147993575 chr7:145444386-147749019 244556 0.04637 NA - NA NA NA NA NA NA NA NA NA NA 11716281_a_at COL18A1 collagen, type XVIII, alpha 1 Extracellular Space other collagenase clostridiumrs2274808 histolyticum chr21:45731055 chr21:45649525-45758061 0 0.00005 X NA NA NA NA NA NA NA NA NA NA NA 11716281_a_at COL18A1 collagen, type XVIII, alpha 1 Extracellular Space other collagenase clostridiumrs11702425 histolyticum chr21:45732783 chr21:45649525-45758061 0 0.04029 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11725124_at CST7 cystatin F (leukocystatin) Extracellular Space other rs4815311 chr20:24707693 chr20:24877866-24888561 170173 0.00033 X NA Excluded NA NA NA NA NA NA NA NA NA NA 11741500_a_at DAGLB diacylglycerol lipase, beta Plasma Membrane enzyme rs1880118 chr7:6401745 chr7:6415273-6454168 13528 0.00000 X NA NA NA NA NA NA NA NA NA NA NA 11741500_a_at DAGLB diacylglycerol lipase, beta Plasma Membrane enzyme rs836472 chr7:6401429 chr7:6415273-6454168 13844 0.00000 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11741500_a_at DAGLB diacylglycerol lipase, beta Plasma Membrane enzyme rs9374 chr7:6408896 chr7:6415273-6454168 6377 0.00000 NA NA NA NA NA NA NA NA NA NA 11741500_a_at DAGLB diacylglycerol lipase, beta Plasma Membrane enzyme rs7792987 chr7:6461542 chr7:6415273-6454168 7374 0.01142 NA NA NA NA NA NA 11733149_a_at DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 Cytoplasm enzyme rs12555576 chr9:32421306 chr9:32445301-32516322 23995 0.00067 NA NA NA NA NA NA NA NA 11723899_a_at DHRS9 dehydrogenase/reductase (SDR family) member 9 Cytoplasm enzyme rs2302698 chr2:169671675 chr2:169629545-169660925 10750 0.00043 X NA NA NA NA NA NA NA NA NA NA NA NA 11764037_s_at DNAJA1 DnaJ (Hsp40) homolog, subfamily A, member 1 Nucleus other rs13297389 chr9:33092409 chr9:33015209-33029062 63347 0.04350 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11735193_x_at EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 Plasma Membrane G-protein coupled receptor rs2732794 chr19:14707335 chr19:14704205-14750353 0 0.03938 X NA NA - NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs11135482 chr5:96247182 chr5:96237400-96281154 0 0.00000 NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs27747 chr5:96385668 chr5:96237400-96281154 104514 0.00000 NA NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs27712 chr5:96389819 chr5:96237400-96281154 108665 0.00000 NA NA NA NA NA NA NA NA NA NA A/HA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs2617434 chr5:96297394 chr5:96237400-96281154 16240 0.00000 NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs18059 chr5:96377824 chr5:96237400-96281154 96670 0.00001 NA NA NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs4869316 chr5:96259219 chr5:96237400-96281154 0 0.00016 NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs2549779 chr5:96242143 chr5:96237400-96281154 0 0.00164 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs2927610 chr5:96226526 chr5:96237400-96281154 10874 0.00518 NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs27433 chr5:96135691 chr5:96237400-96281154 101709 0.00931 NA NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs10045403 chr5:96173489 chr5:96237400-96281154 63911 0.01748 NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs2927614 chr5:96224235 chr5:96237400-96281154 13165 0.02355 NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs2617442 chr5:96227335 chr5:96237400-96281154 10065 0.02674 NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs4869317 chr5:96317760 chr5:96237400-96281154 36606 0.02938 NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs26653 chr5:96165006 chr5:96237400-96281154 72394 0.01809 NA NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs2549780 chr5:96242540 chr5:96237400-96281154 0 0.02880 NA NA NA NA NA NA NA NA NA NA 11747137_x_at ERAP2 endoplasmic reticulum aminopeptidase 2 Cytoplasm peptidase rs17531248 chr5:96385699 chr5:96237400-96281154 104545 0.03040 NA NA NA NA NA NA 11750454_a_at ETV7 ets variant 7 Nucleus transcription regulator rs7766404 chr6:36471797 chr6:36441950-36463445 8352 0.00004 L NA NA NA NA NA L NA NA NA NA NA 11720023_a_at FAM118A family with sequence similarity 118, member A unknown other rs13057793 chr22:44121878 chr22:44083745-44116498 5380 0.00259 X NA Excluded NA NA NA NA NA NA NA NA NA NA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs2061831 chr8:11377292 chr8:11316383-11361686 15606 0.00000 NA NA L NA NA NA NA NA NA L A/HA A/HA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs62489069 chr8:11375793 chr8:11316383-11361686 14107 0.00002 NA NA L NA NA NA NA NA NA L 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs2736350 chr8:11398961 chr8:11316383-11361686 37275 0.00023 NA NA NA NA NA NA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs1478897 chr8:11432641 chr8:11316383-11361686 70955 0.00362 X NA NA NA NA L NA NA NA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs2736346 chr8:11396521 chr8:11316383-11361686 34835 0.00983 X NA NA NA NA NA NA NA NA NA NA NA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs12674768 chr8:11408956 chr8:11316383-11361686 47270 0.01200 X NA NA NA NA NA NA NA NA NA NA NA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs7000824 chr8:11355694 chr8:11316383-11361686 0 0.01733 NA NA NA NA NA NA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs13257831 chr8:11370374 chr8:11316383-11361686 8688 0.00539 X NA NA NA L NA NA NA NA NA NA L 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs9644737 chr8:11306415 chr8:11316383-11361686 9968 0.02398 X NA NA NA L NA NA NA NA NA NA L NA NA NA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs12549796 chr8:11327107 chr8:11316383-11361686 0 0.02437 X NA NA - NA NA NA NA NA NA NA NA NA NA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs11250149 chr8:11477370 chr8:11316383-11361686 115684 0.02844 X NA NA NA L NA NA NA NA NA NA L 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs1478894 chr8:11486163 chr8:11316383-11361686 124477 0.03585 NA NA - NA NA L NA NA NA NA NA L 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs899366 chr8:11467894 chr8:11316383-11361686 106208 0.03749 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs11773929 chr8:11350271 chr8:11316383-11361686 0 0.02814 NA NA NA NA NA NA 11723789_a_at FAM167A family with sequence similarity 167, member A unknown other rs10088942 chr8:11322778 chr8:11316383-11361686 0 0.04112 NA NA L NA NA NA NA NA NA L 11729673_s_at FAM200B family with sequence similarity 200, member B unknown other rs73224660 chr4:15323860 chr4:15292450-15301160 22700 0.01733 NA NA NA NA NA NA NA NA NA 11723025_at FAM26F family with sequence similarity 26, member F unknown other rs41289932 chr6:116891543 chr6:116889249-116891626 0 0.01786 NA NA NA NA 11725847_s_at FAM76B family with sequence similarity 76, member B unknown other rs627568 chr11:95208901 chr11:95141754-95162602 46299 0.00062 X NA NA NA NA NA NA NA NA NA NA NA 11725847_s_at FAM76B family with sequence similarity 76, member B unknown other rs1255182 chr11:95112039 chr11:95141754-95162602 29715 0.03902 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11724171_a_at FCHO2 FCH domain only 2 Cytoplasm other rs13157620 chr5:72165360 chr5:72287564-72422104 122204 0.04570 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11744140_a_at FOLR3 folate receptor 3 (gamma) Extracellular Space other rs3900852 chr11:71640777 chr11:71524419-71528582 112195 0.04579 X NA NA Excluded NA NA NA NA NA NA NA NA NA NA 11728067_at PTGDR2 prostaglandin D2 receptor 2 Plasma Membrane G-protein coupled receptor rs77021462 chr11:60542553 chr11:60374974-60380020 162533 0.01942 11718579_at GSTM3 glutathione S-transferase mu 3 (brain) Cytoplasm enzyme rs568686 chr1:109975298 chr1:110078077-110085183 102779 0.03362 NA NA NA NA NA NA NA NA NA NA NA 11719246_a_at GSTT1 glutathione S-transferase theta 1 Cytoplasm enzyme rs2000467 chr22:22571533 chr22:22706141-22714284 134608 0.02814 X NA NA NA NA NA NA NA NA NA NA NA NA 11724021_at HIST1H2BD histone cluster 1, H2bd Nucleus other rs9379829 chr6:26280198 chr6:26266328-26266848 13350 0.00080 X NA NA NA NA A NA NA NA NA NA A NA 11724021_at HIST1H2BD histone cluster 1, H2bd Nucleus other rs9379831 chr6:26283831 chr6:26266328-26266848 16983 0.02904 X NA NA NA NA HA NA NA NA NA NA HA NA 11724021_at HIST1H2BD histone cluster 1, H2bd Nucleus other rs10946808 chr6:26341366 chr6:26266328-26266848 74518 0.04923 X NA NA NA NA HA NA NA NA NA NA HA NA 11724021_at HIST1H2BD histone cluster 1, H2bd Nucleus other rs3778279 chr6:26433442 chr6:26266328-26266848 166594 0.04994 X NA A HA L HA NA NA HA HA L HA NA 11738783_at HIST1H3A (includes others)histone cluster 1, H3a Nucleus other rs198811 chr6:26236425 chr6:26153618-26154075 82350 0.00430 NA HA NA NA NA NA HA NA 11738783_at HIST1H3A (includes others)histone cluster 1, H3a Nucleus other rs198854 chr6:26212036 chr6:26153618-26154075 57961 0.02437 NA NA HA L NA NA NA HA L 11738783_at HIST1H3A (includes others)histone cluster 1, H3a Nucleus other rs1324088 chr6:25949101 chr6:26153618-26154075 204517 0.04452 HA HA L HA NA NA HA HA L HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2256543 chr6:30045812 chr6:30018288-30021639 24173 0.00000 HA L L HA HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs6457110 chr6:30041860 chr6:30018288-30021639 20221 0.00000 L L A 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs9258881 chr6:29945121 chr6:30018288-30021639 73167 0.00000 L Excluded NA HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs3823374 chr6:30052127 chr6:30018288-30021639 30488 0.00000 NA L HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2523946 chr6:30049922 chr6:30018288-30021639 28283 0.00000 HA NA NA HA HA HA HA NA NA HA HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2523399 chr6:29808058 chr6:30018288-30021639 210230 0.00000 HA NA Excluded HA HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2394250 chr6:30051635 chr6:30018288-30021639 29996 0.00000 HA NA NA HA NA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs7762253 chr6:29784802 chr6:30018288-30021639 233486 0.00000 NA HA HA L HA NA L HA HA L 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1737043 chr6:29844026 chr6:30018288-30021639 174262 0.00000 L NA HA NA L HA NA HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs9393989 chr6:30148063 chr6:30018288-30021639 126424 0.00000 L HA HA HA HA A HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2735052 chr6:29809543 chr6:30018288-30021639 208745 0.00000 NA HA HA A HA L L HA HA A 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2508037 chr6:30026415 chr6:30018288-30021639 4776 0.00000 NA NA HA HA L 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs3823376 chr6:30052163 chr6:30018288-30021639 30524 0.00002 L HA L 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs9357086 chr6:29886008 chr6:30018288-30021639 132280 0.00000 NA HA L HA L HA L HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1156534 chr6:30173131 chr6:30018288-30021639 151492 0.00005 NA NA HA L 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs3094165 chr6:29941520 chr6:30018288-30021639 76768 0.00006 HA NA NA NA HA A HA NA NA NA HA A 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs3807031 chr6:30141863 chr6:30018288-30021639 120224 0.00005 NA L NA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs259940 chr6:30119913 chr6:30018288-30021639 98274 0.00007 L HA HA HA HA L L HA HA HA HA L 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2256922 chr6:30048793 chr6:30018288-30021639 27154 0.00008 HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2523990 chr6:30185208 chr6:30018288-30021639 163569 0.00015 HA HA NA HA HA HA HA NA HA HA Page 111 of 111 Diabetes

11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1737069 chr6:29838709 chr6:30018288-30021639 179579 0.00019 HA NA HA NA HA HA NA HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1150743 chr6:30100240 chr6:30018288-30021639 78601 0.00019 NA HA HA NA HA NA NA HA HA NA HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1736926 chr6:29800541 chr6:30018288-30021639 217747 0.00028 A NA HA L HA A HA NA HA L 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1737060 chr6:29840948 chr6:30018288-30021639 177340 0.00028 A Excluded NA HA L 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2735046 chr6:29842077 chr6:30018288-30021639 176211 0.00010 HA A HA HA HA HA A HA HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1627567 chr6:29790845 chr6:30018288-30021639 227443 0.00039 L NA HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1611715 chr6:29937461 chr6:30018288-30021639 80827 0.00013 L A HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs4713243 chr6:29828940 chr6:30018288-30021639 189348 0.00011 NA A HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs3893464 chr6:30043229 chr6:30018288-30021639 21590 0.00075 L NA NA NA HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs62390186 chr6:30182421 chr6:30018288-30021639 160782 0.00117 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1264708 chr6:30165133 chr6:30018288-30021639 143494 0.00190 NA NA NA NA HA NA NA NA NA NA HA L 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1736913 chr6:29812379 chr6:30018288-30021639 205909 0.00223 HA HA NA HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs62390201 chr6:30189609 chr6:30018288-30021639 167970 0.00283 NA HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2857436 chr6:30214049 chr6:30018288-30021639 192410 0.00318 NA NA L HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2022065 chr6:30229439 chr6:30018288-30021639 207800 0.00415 HA NA NA L HA HA HA L NA L HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs6457144 chr6:30171347 chr6:30018288-30021639 149708 0.00514 NA NA NA HA HA NA NA NA HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs3823363 chr6:30051694 chr6:30018288-30021639 30055 0.00680 NA NA HA A 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1264704 chr6:30173298 chr6:30018288-30021639 151659 0.00768 L L HA L HA L L L HA L HA L 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs7767857 chr6:30182177 chr6:30018288-30021639 160538 0.00460 NA HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2517653 chr6:30229164 chr6:30018288-30021639 207525 0.00983 L NA HA HA L L L HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2844806 chr6:30041418 chr6:30018288-30021639 19779 0.01133 NA NA HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs757257 chr6:30250437 chr6:30018288-30021639 228798 0.01370 HA L HA HA HA L HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs3132726 chr6:29931585 chr6:30018288-30021639 86703 0.00843 HA HA HA NA HA NA HA HA HA NA HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs3131875 chr6:29774090 chr6:30018288-30021639 244198 0.01417 - NA HA A NA HA A 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs259933 chr6:30113284 chr6:30018288-30021639 91645 0.01449 NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1008403 chr6:30240806 chr6:30018288-30021639 219167 0.01469 NA NA HA NA L NA NA NA HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs1150739 chr6:30139324 chr6:30018288-30021639 117685 0.01553 L NA A L HA A L NA A L HA A 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2074472 chr6:30264475 chr6:30018288-30021639 242836 0.01601 NA L HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs2523765 chr6:29925085 chr6:30018288-30021639 93203 0.00407 NA HA HA L 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs9261401 chr6:30176128 chr6:30018288-30021639 154489 0.01615 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs259919 chr6:30133482 chr6:30018288-30021639 111843 0.02598 NA HA HA L HA NA NA HA HA L HA NA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs9261438 chr6:30197259 chr6:30018288-30021639 175620 0.02641 HA L HA HA HA L HA HA 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs28400887 chr6:30183882 chr6:30018288-30021639 162243 0.03022 11762150_x_at HLA-A major histocompatibility complex, class I, A Plasma Membrane other rs9260794 chr6:30047656 chr6:30018288-30021639 26017 0.03167 HA NA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2524074 chr6:31352000 chr6:31344509-31347834 4166 0.00000 HA HA HA NA HA HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2524069 chr6:31352768 chr6:31344509-31347834 4934 0.00000 HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2442749 chr6:31460019 chr6:31344509-31347834 112185 0.00000 NA HA Excluded HA HA NA NA HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs4143332 chr6:31456344 chr6:31344509-31347834 108510 0.00000 HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3130477 chr6:31536899 chr6:31344509-31347834 189065 0.00000 HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3130614 chr6:31584437 chr6:31344509-31347834 236603 0.00000 HA NA HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2535296 chr6:31168198 chr6:31344509-31347834 176311 0.00000 HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3130557 chr6:31202682 chr6:31344509-31347834 141827 0.00000 HA HA HA NA HA HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2517546 chr6:31117034 chr6:31344509-31347834 227475 0.00001 HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3132510 chr6:31280130 chr6:31344509-31347834 64379 0.00002 HA HA L HA HA HA HA L 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2523554 chr6:31439808 chr6:31344509-31347834 91974 0.00003 HA HA HA HA NA HA HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2853935 chr6:31361857 chr6:31344509-31347834 14023 0.00005 L HA HA HA L L HA HA HA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2233956 chr6:31189184 chr6:31344509-31347834 155325 0.00008 HA HA HA HA NA HA HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs887468 chr6:31249502 chr6:31344509-31347834 95007 0.00031 HA HA HA L NA HA HA HA HA L 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs720465 chr6:31233756 chr6:31344509-31347834 110753 0.00017 NA HA HA HA NA NA HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs130066 chr6:31230294 chr6:31344509-31347834 114215 0.00032 HA HA L 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2844498 chr6:31584833 chr6:31344509-31347834 236999 0.00044 HA HA HA HA NA HA HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2246954 chr6:31373241 chr6:31344509-31347834 25407 0.00048 L NA HA HA HA L NA HA HA HA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs9266669 chr6:31456056 chr6:31344509-31347834 108222 0.00048 HA HA NA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs1793891 chr6:31329677 chr6:31344509-31347834 14832 0.00078 HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3869109 chr6:31292175 chr6:31344509-31347834 52334 0.00079 HA NA NA HA HA A HA NA NA HA HA HA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3130696 chr6:31351863 chr6:31344509-31347834 4029 0.00101 HA HA HA HA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2596530 chr6:31495352 chr6:31344509-31347834 147518 0.00207 A HA HA NA A L HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs9263993 chr6:31300745 chr6:31344509-31347834 43764 0.00262 L L HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3094600 chr6:31455123 chr6:31344509-31347834 107289 0.00308 HA HA NA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2248462 chr6:31554775 chr6:31344509-31347834 206941 0.00294 HA HA HA HA HA L 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3094228 chr6:31537906 chr6:31344509-31347834 190072 0.00548 HA HA HA NA HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs9264942 chr6:31382359 chr6:31344509-31347834 34525 0.00573 HA HA HA HA HA NA HA HA HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2844546 chr6:31452636 chr6:31344509-31347834 104802 0.00624 HA HA HA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs6904669 chr6:31300775 chr6:31344509-31347834 43734 0.00393 A HA HA L A HA HA L 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2523708 chr6:31559258 chr6:31344509-31347834 211424 0.00768 HA HA HA L 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2894181 chr6:31282506 chr6:31344509-31347834 62003 0.00854 - A HA HA A HA HA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2524084 chr6:31349618 chr6:31344509-31347834 1784 0.00865 HA HA HA HA HA HA HA HA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2844502 chr6:31553195 chr6:31344509-31347834 205361 0.00944 HA HA A NA HA HA HA HA A 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2240064 chr6:31222552 chr6:31344509-31347834 121957 0.00503 HA HA HA A HA NA HA HA HA A HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2517403 chr6:31174988 chr6:31344509-31347834 169521 0.00629 NA HA Excluded HA HA L NA HA HA HA L 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2524070 chr6:31352499 chr6:31344509-31347834 4665 0.01133 HA NA NA L NA HA NA NA L HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs1634761 chr6:31382006 chr6:31344509-31347834 34172 0.01142 NA HA HA HA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3130944 chr6:31304650 chr6:31344509-31347834 39859 0.01324 HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2853923 chr6:31373716 chr6:31344509-31347834 25882 0.02043 NA NA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs1265087 chr6:31217789 chr6:31344509-31347834 126720 0.01819 A HA HA NA NA A HA HA HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs2395471 chr6:31348671 chr6:31344509-31347834 837 0.02359 HA HA HA HA A HA HA HA HA A 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3823402 chr6:31189722 chr6:31344509-31347834 154787 0.03104 HA A L HA A L 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs4713460 chr6:31455777 chr6:31344509-31347834 107943 0.03127 HA NA HA L HA HA NA HA L 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs9263969 chr6:31294513 chr6:31344509-31347834 49996 0.03265 A NA L L HA NA A NA L L HA NA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs4713429 chr6:31128996 chr6:31344509-31347834 215513 0.04626 HA A L HA A 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs6909636 chr6:31454578 chr6:31344509-31347834 106744 0.04530 HA L HA HA L HA 11715316_x_at HLA-C major histocompatibility complex, class I, C Plasma Membrane other rs3828914 chr6:31573798 chr6:31344509-31347834 225964 0.04982 HA NA NA L HA NA HA NA NA A HA NA 11761071_at HLA-DOB major histocompatibility complex, class II, DO beta Plasma Membrane transmembrane receptor rs4148876 chr6:32904770 chr6:32888519-32892803 11967 0.00032 X HA L HA HA L HA 11761071_at HLA-DOB major histocompatibility complex, class II, DO beta Plasma Membrane transmembrane receptor rs117821 chr6:32906689 chr6:32888519-32892803 13886 0.00734 NA HA NA A L HA NA HA NA 11761071_at HLA-DOB major histocompatibility complex, class II, DO beta Plasma Membrane transmembrane receptor rs3763354 chr6:32894895 chr6:32888519-32892803 2092 0.01142 X L NA NA L NA NA NA 11761071_at HLA-DOB major histocompatibility complex, class II, DO beta Plasma Membrane transmembrane receptor rs241429 chr6:32911818 chr6:32888519-32892803 19015 0.01778 HA HA HA NA HA HA HA NA 11761071_at HLA-DOB major histocompatibility complex, class II, DO beta Plasma Membrane transmembrane receptor rs453779 chr6:33083359 chr6:32888519-32892803 190556 0.04038 A L HA L HA HA A L HA L HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs9277357 chr6:33157957 chr6:33151738-33162954 0 0.00000 NA HA HA HA L HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs3117230 chr6:33183613 chr6:33151738-33162954 20659 0.00000 X L HA HA NA HA HA L HA HA NA HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs9277489 chr6:33161920 chr6:33151738-33162954 0 0.00000 X L L HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs406477 chr6:33113622 chr6:33151738-33162954 38116 0.00002 X HA NA HA HA HA NA HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs2301224 chr6:33146347 chr6:33151738-33162954 5391 0.00003 X NA NA HA HA NA NA L NA HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs6911848 chr6:33183237 chr6:33151738-33162954 20283 0.00011 X A HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs429916 chr6:33086565 chr6:33151738-33162954 65173 0.00008 X L HA HA A HA L HA HA A HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs3130235 chr6:33205360 chr6:33151738-33162954 42406 0.00007 X A NA NA L A A HA NA NA L 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs380468 chr6:33109466 chr6:33151738-33162954 42272 0.00046 X NA NA HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs2127676 chr6:32957819 chr6:33151738-33162954 193919 0.00206 HA L 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs9500927 chr6:33069339 chr6:33151738-33162954 82399 0.00342 X HA HA HA HA HA HA HA HA HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs2071025 chr6:33251734 chr6:33151738-33162954 88780 0.00707 X NA NA NA A NA NA L A HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs2076312 chr6:33250140 chr6:33151738-33162954 87186 0.00565 X L NA L L L HA HA NA L L 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs620202 chr6:33049888 chr6:33151738-33162954 101850 0.01113 HA HA HA NA HA HA HA HA HA NA HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs194675 chr6:33013724 chr6:33151738-33162954 138014 0.00950 NA L HA HA NA L HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs3130216 chr6:33185249 chr6:33151738-33162954 22295 0.03040 X NA NA HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs1480380 chr6:33021224 chr6:33151738-33162954 130514 0.04512 X NA HA HA HA HA HA NA HA HA HA HA HA 11760799_x_at HLA-DPB1 major histocompatibility complex, class II, DP beta 1 Plasma Membrane transmembrane receptor rs12216336 chr6:33075719 chr6:33151738-33162954 76019 0.04848 X NA NA NA HA A L NA NA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9272219 chr6:32710247 chr6:32713161-32719406 2914 0.00000 HA Excluded HA HA HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs2858332 chr6:32789139 chr6:32713161-32719406 69733 0.00000 L Excluded HA HA L HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs2858867 chr6:32683303 chr6:32713161-32719406 29858 0.00000 HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs3117099 chr6:32466248 chr6:32713161-32719406 246913 0.00000 L HA HA HA HA HA L HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs1964995 chr6:32557389 chr6:32713161-32719406 155772 0.00000 HA HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs3135382 chr6:32491419 chr6:32713161-32719406 221742 0.00000 HA HA HA HA HA HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs7774434 chr6:32765556 chr6:32713161-32719406 46150 0.00000 HA HA Excluded HA HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs1794282 chr6:32774504 chr6:32713161-32719406 55098 0.00000 HA HA HA A 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs3135363 chr6:32497626 chr6:32713161-32719406 215535 0.00000 HA HA HA HA HA HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9268507 chr6:32485517 chr6:32713161-32719406 227644 0.00000 L HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9268557 chr6:32497283 chr6:32713161-32719406 215878 0.00000 HA Excluded A HA HA HA A HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs6906021 chr6:32734289 chr6:32713161-32719406 14883 0.00000 NA HA HA NA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs7762279 chr6:32863268 chr6:32713161-32719406 143862 0.00000 HA Excluded HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs3998158 chr6:32789970 chr6:32713161-32719406 70564 0.00000 HA L HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs6457617 chr6:32771829 chr6:32713161-32719406 52423 0.00001 HA HA Excluded A HA HA HA HA A HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9275698 chr6:32795951 chr6:32713161-32719406 76545 0.00009 HA HA Excluded HA HA HA HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs477515 chr6:32677669 chr6:32713161-32719406 35492 0.00003 Excluded HA HA HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs17500468 chr6:32819156 chr6:32713161-32719406 99750 0.00115 HA HA HA NA NA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9271488 chr6:32696978 chr6:32713161-32719406 16183 0.00008 HA HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9276612 chr6:32850690 chr6:32713161-32719406 131284 0.00073 NA HA HA NA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9275652 chr6:32793800 chr6:32713161-32719406 74394 0.00034 HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9276584 chr6:32838813 chr6:32713161-32719406 119407 0.00034 HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs241429 chr6:32911818 chr6:32713161-32719406 192412 0.00192 HA HA HA NA HA HA HA NA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9268516 chr6:32487467 chr6:32713161-32719406 225694 0.00023 HA HA HA HA HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs241424 chr6:32912912 chr6:32713161-32719406 193506 0.00422 HA HA HA A HA A HA HA HA A HA A 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs2071550 chr6:32838918 chr6:32713161-32719406 119512 0.00563 HA HA L HA L HA HA L HA L 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs2395166 chr6:32496253 chr6:32713161-32719406 216908 0.01184 HA HA HA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs3135392 chr6:32517220 chr6:32713161-32719406 195941 0.00328 L Excluded HA HA HA L HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9275141 chr6:32759095 chr6:32713161-32719406 39689 0.00311 HA NA Excluded HA HA HA NA HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs2127676 chr6:32957819 chr6:32713161-32719406 238413 0.00473 HA L Diabetes Page 112 of 111

11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9275601 chr6:32790642 chr6:32713161-32719406 71236 0.02394 HA HA L HA HA HA HA L HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9276909 chr6:32958817 chr6:32713161-32719406 239411 0.01171 L HA NA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9268614 chr6:32510756 chr6:32713161-32719406 202405 0.00426 HA L HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs3892710 chr6:32790840 chr6:32713161-32719406 71434 0.02071 HA Excluded L HA HA HA L HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9273363 chr6:32734250 chr6:32713161-32719406 14844 0.04403 - - HA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs2857209 chr6:32849896 chr6:32713161-32719406 130490 0.03106 A A L 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs241448 chr6:32904662 chr6:32713161-32719406 185256 0.04975 HA HA HA HA HA NA HA HA HA HA HA NA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9268515 chr6:32487273 chr6:32713161-32719406 225888 0.01930 L HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9268528 chr6:32491086 chr6:32713161-32719406 222075 0.02520 HA HA Excluded L HA HA HA HA L HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs660895 chr6:32685358 chr6:32713161-32719406 27803 0.03081 - Excluded NA HA - NA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs2857211 chr6:32848420 chr6:32713161-32719406 129014 0.03667 HA L NA HA L NA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs9275338 chr6:32775321 chr6:32713161-32719406 55915 0.04712 - NA HA HA 11756083_x_at HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1 Plasma Membrane transmembrane receptor rs5000634 chr6:32771542 chr6:32713161-32719406 52136 0.04886 HA HA Excluded L HA HA 11743168_at IDO1 indoleamine 2,3-dioxygenase 1 Cytoplasm enzyme rs1035280 chr8:39953434 chr8:39890485-39905102 48332 0.02223 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11761686_at IFIH1 interferon induced with helicase C domain 1 Nucleus enzyme rs901303 chr2:163124693 chr2:162831836-162883285 241408 0.03744 NA NA L NA NA NA NA NA NA L NA NA NA NA 11749598_a_at IL18RAP interleukin 18 receptor accessory protein Plasma Membrane transmembrane receptor rs6706002 chr2:102372536 chr2:102401686-102435454 29150 0.01430 X NA NA L NA NA L NA NA NA L NA 11749598_a_at IL18RAP interleukin 18 receptor accessory protein Plasma Membrane transmembrane receptor rs1833174 chr2:102401275 chr2:102401686-102435454 411 0.02647 NA NA NA L NA NA NA L NA 11749598_a_at IL18RAP interleukin 18 receptor accessory protein Plasma Membrane transmembrane receptor rs13021177 chr2:102422925 chr2:102401686-102435454 0 0.02647 X NA NA L NA NA L NA NA NA L NA 11719141_a_at INSIG2 insulin induced gene 2 Cytoplasm other rs17047801 chr2:118603973 chr2:118562520-118584066 19907 0.00586 X NA NA NA NA NA NA NA NA 11719141_a_at INSIG2 insulin induced gene 2 Cytoplasm other rs13025020 chr2:118643425 chr2:118562520-118584066 59359 0.00854 NA L NA NA NA NA L NA NA NA 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs6969930 chr7:128417549 chr7:128365230-128377322 40227 0.00000 X NA NA NA NA NA NA NA NA NA NA L 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs6960994 chr7:128479893 chr7:128365230-128377322 102571 0.00000 X NA NA NA NA NA NA NA NA NA NA NA NA NA 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs11770589 chr7:128376724 chr7:128365230-128377322 0 0.00000 NA NA NA NA NA NA NA NA NA NA 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs6974262 chr7:128462893 chr7:128365230-128377322 85571 0.00000 NA NA NA NA NA NA NA NA NA NA 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs2167273 chr7:128476649 chr7:128365230-128377322 99327 0.00001 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs3807302 chr7:128432093 chr7:128365230-128377322 54771 0.00001 NA NA NA NA NA NA NA NA L 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs1874328 chr7:128372340 chr7:128365230-128377322 0 0.00009 X NA NA NA NA NA NA NA NA NA NA NA 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs12155247 chr7:128498349 chr7:128365230-128377322 121027 0.00032 NA NA NA NA 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs3778753 chr7:128367278 chr7:128365230-128377322 0 0.00043 NA NA L NA NA NA L 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs11761199 chr7:128369071 chr7:128365230-128377322 0 0.00064 X NA NA NA L NA NA NA NA NA NA L 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs1901198 chr7:128497025 chr7:128365230-128377322 119703 0.00123 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs3807304 chr7:128431769 chr7:128365230-128377322 54447 0.00133 NA NA NA NA NA NA 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs3757385 chr7:128364540 chr7:128365230-128377322 690 0.00906 NA NA NA NA NA NA NA NA NA L 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs2305323 chr7:128420958 chr7:128365230-128377322 43636 0.00960 X NA NA NA NA NA NA NA NA NA NA NA 11726687_a_at IRF5 interferon regulatory factor 5 Nucleus transcription regulator rs11768806 chr7:128360364 chr7:128365230-128377322 4866 0.01370 NA NA NA NA NA NA 11744600_a_at TESPA1 thymocyte expressed, positive selection associated 1 Cytoplasm other rs1801876 chr12:53630291 chr12:53630196-53661889 0 0.00198 NA NA NA NA NA NA NA NA NA NA NA 11742301_x_at KIR2DL3 (includes others)killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 3Plasma Membrane other rs35987710 chr19:59937550 chr19:59941786-59956315 4236 0.02069 NA NA NA NA NA NA 11742301_x_at KIR2DL3 (includes others)killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 3Plasma Membrane other rs1749282 chr19:59886633 chr19:59941786-59956315 55153 0.02372 NA NA NA NA NA NA NA NA NA NA NA 11733718_x_at LAIR2 leukocyte-associated immunoglobulin-like receptor 2 Plasma Membrane other rs4806802 chr19:59865215 chr19:59705825-59713707 151508 0.00385 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11733718_x_at LAIR2 leukocyte-associated immunoglobulin-like receptor 2 Plasma Membrane other rs2042290 chr19:59705583 chr19:59705825-59713707 242 0.02710 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11721243_a_at LAP3 leucine aminopeptidase 3 Cytoplasm peptidase rs1860598 chr4:17266458 chr4:17188025-17218688 47770 0.00010 X NA NA NA NA NA NA NA NA NA NA NA NA 11730656_a_at LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), memberExtracellular 3 Space other rs398227 chr19:59484860 chr19:59491669-59496077 6809 0.00002 NA NA 11730656_a_at LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), memberExtracellular 3 Space other rs651279 chr19:59505574 chr19:59491669-59496077 9497 0.00004 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11730656_a_at LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), memberExtracellular 3 Space other rs11084329 chr19:59527583 chr19:59491669-59496077 31506 0.00873 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11730656_a_at LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), memberExtracellular 3 Space other rs4806741 chr19:59502182 chr19:59491669-59496077 6105 0.02216 NA NA NA NA NA NA NA NA NA NA NA NA 11738698_x_at LILRA5 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 5 Membrane other rs34341121 chr19:59522169 chr19:59514366-59516180 5989 0.00085 NA NA NA NA NA NA NA 11738698_x_at LILRA5 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 5 Membrane other rs34450379 chr19:59457867 chr19:59514366-59516180 56499 0.01988 NA NA NA NA NA NA 11738698_x_at LILRA5 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), memberPlasma 5 Membrane other rs12984962 chr19:59461017 chr19:59514366-59516180 53349 0.02147 NA NA NA NA NA NA 11725418_a_at LPCAT2 lysophosphatidylcholine acyltransferase 2 Cytoplasm enzyme rs243836 chr16:54091737 chr16:54100414-54178082 8677 0.00001 NA NA NA NA NA NA NA NA NA NA NA 11740275_a_at LRRC25 leucine rich repeat containing 25 unknown other rs7251067 chr19:18461056 chr19:18362955-18369415 91641 0.02116 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11723771_a_at MASTL microtubule associated serine/threonine kinase-like Cytoplasm kinase rs10829163 chr10:27357846 chr10:27483759-27515854 125913 0.00000 X NA NA NA NA NA NA NA NA NA NA NA NA 11737839_a_at MBOAT7 membrane bound O-acyltransferase domain containing 7 Plasma Membrane other rs10424062 chr19:59616032 chr19:59373853-59385545 230487 0.04561 NA NA NA NA NA NA 11722132_a_at MGAT3 mannosyl (beta-1,4-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferaseCytoplasm enzyme rs5757721 chr22:38277520 chr22:38183271-38218143 59377 0.02437 NA NA NA NA NA NA NA NA NA NA NA NA 11722132_a_at MGAT3 mannosyl (beta-1,4-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferaseCytoplasm enzyme rs1010169 chr22:38108113 chr22:38183271-38218143 75158 0.04838 NA NA NA NA NA L NA NA NA NA NA NA 11754705_a_at MRPL43 mitochondrial ribosomal protein L43 Cytoplasm translation regulator rs1886276 chr10:102637171 chr10:102736017-102737262 98846 0.04112 X NA NA NA NA NA NA NA NA NA NA NA 11743645_s_at MXRA7 matrix-remodelling associated 7 unknown other rs9898576 chr17:72112871 chr17:72187248-72218651 74377 0.04729 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11725136_a_at MYOM2 myomesin (M-protein) 2, 165kDa Cytoplasm other rs9314456 chr8:2096739 chr8:1980565-2080786 15953 0.00000 X NA NA NA NA NA NA NA NA NA 11725136_a_at MYOM2 myomesin (M-protein) 2, 165kDa Cytoplasm other rs1866717 chr8:2047956 chr8:1980565-2080786 0 0.03355 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11719186_a_at N4BP2L2 NEDD4 binding protein 2-like 2 Nucleus other rs9595617 chr13:31955345 chr13:31989031-32010932 33686 0.00000 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11719186_a_at N4BP2L2 NEDD4 binding protein 2-like 2 Nucleus other rs169600 chr13:31953620 chr13:31989031-32010932 35411 0.02622 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11724255_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme rs7970893 chr12:111875062 chr12:111829122-111840212 34850 0.00184 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11724255_a_at OAS1 2-5-oligoadenylate synthetase 1, 40/46kDa Cytoplasm enzyme rs10744793 chr12:111938246 chr12:111829122-111840212 98034 0.02423 X NA NA NA NA NA NA NA NA NA 11726778_at OAS2 2-5-oligoadenylate synthetase 2, 69/71kDa Cytoplasm enzyme rs2240188 chr12:111888067 chr12:111900657-111910992 12590 0.00001 NA NA NA NA NA NA NA NA NA NA NA NA 11726778_at OAS2 2-5-oligoadenylate synthetase 2, 69/71kDa Cytoplasm enzyme rs7970893 chr12:111875062 chr12:111900657-111910992 25595 0.00438 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11732403_a_at OGFRL1 opioid growth factor receptor-like 1 unknown other rs9355001 chr6:72191056 chr6:72055198-72068692 122364 0.03721 X NA NA NA NA NA NA NA NA NA NA NA NA 11735165_s_at OSBPL5 oxysterol binding protein-like 5 Cytoplasm other rs7102375 chr11:3136518 chr11:3064922-3143158 0 0.00322 X NA NA NA NA NA NA NA NA 11735165_s_at OSBPL5 oxysterol binding protein-like 5 Cytoplasm other rs4758538 chr11:3118970 chr11:3064922-3143158 0 0.01456 NA NA NA NA NA NA 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs258243 chr5:102195531 chr5:102229426-102394705 33895 0.00000 NA NA NA NA NA NA NA NA L 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs2431531 chr5:102135998 chr5:102229426-102394705 93428 0.00000 NA NA NA NA NA NA NA NA NA NA L 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs469489 chr5:102189925 chr5:102229426-102394705 39501 0.00000 NA L NA NA NA NA NA NA L 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs187717 chr5:102128424 chr5:102229426-102394705 101002 0.00000 NA NA NA NA NA NA NA NA NA NA NA 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs3733939 chr5:102338065 chr5:102229426-102394705 0 0.00000 X NA NA NA NA NA NA NA NA NA NA NA NA L 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs34374 chr5:102431920 chr5:102229426-102394705 37215 0.00011 X NA NA NA NA NA NA NA NA NA NA NA NA NA L 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs26815 chr5:102571192 chr5:102229426-102394705 176487 0.00017 X NA NA NA NA NA NA NA NA NA NA L 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs32680 chr5:102219614 chr5:102229426-102394705 9812 0.00087 X NA NA NA NA NA L NA NA NA NA NA L 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs6596528 chr5:102333527 chr5:102229426-102394705 0 0.00097 X NA NA NA NA NA NA NA NA NA L 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs26253 chr5:102584866 chr5:102229426-102394705 190161 0.00422 X NA NA NA NA NA NA NA NA NA NA L 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs10038600 chr5:102266401 chr5:102229426-102394705 0 0.00682 X NA NA NA NA NA NA NA NA NA NA NA NA 11740278_s_at PAM peptidylglycine alpha-amidating monooxygenase Plasma Membrane enzyme rs3756582 chr5:102367451 chr5:102229426-102394705 0 0.00730 X NA NA NA NA NA NA NA NA NA L 11724188_x_at PARP10 poly (ADP-ribose) polymerase family, member 10 Nucleus other rs7831595 chr8:145046951 chr8:145123309-145132623 76358 0.04677 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11747110_a_at PASK PAS domain containing serine/threonine kinase Cytoplasm kinase rs13411510 chr2:241664323 chr2:241694188-241737551 29865 0.02598 NA NA NA NA NA NA NA NA NA NA NA NA 11738092_a_at PDE9A phosphodiesterase 9A Cytoplasm enzyme rs2839591 chr21:43159655 chr21:42946931-43068685 90970 0.04468 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11730906_at PDS5B PDS5, regulator of cohesion maintenance, homolog B (S. cerevisiae) Nucleus other rs9595617 chr13:31955345 chr13:32058564-32250158 103219 0.00931 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11723303_at PDZK1IP1 PDZK1 interacting protein 1 Extracellular Space other rs6700838 chr1:47472614 chr1:47421849-47428358 44256 0.01169 NA NA NA NA NA NA NA NA L NA NA NA NA NA 11756898_a_at PGM5 phosphoglucomutase 5 Cytoplasm enzyme rs11142941 chr9:70368029 chr9:70161635-70335796 32233 0.00208 X NA NA NA Excluded NA NA NA NA NA NA NA NA NA 11756898_a_at PGM5 phosphoglucomutase 5 Cytoplasm enzyme rs9644996 chr9:70375735 chr9:70161635-70335796 39939 0.00221 X NA NA NA NA NA NA NA NA NA NA NA NA 11755359_x_at PHACTR4 phosphatase and actin regulator 4 Plasma Membrane other rs10794514 chr1:28532283 chr1:28568680-28699467 36397 0.00049 NA NA NA NA NA NA NA NA NA NA NA NA 11728571_a_at PLCL1 phospholipase C-like 1 Cytoplasm enzyme rs6738825 chr2:198605140 chr2:198377671-198722851 0 0.00099 X NA NA NA NA NA NA NA NA NA NA NA A/HA 11738349_x_at POMZP3 POM121 and ZP3 fusion Nucleus other rs10952936 chr7:75977389 chr7:76077240-76094556 99851 0.03562 NA NA NA NA NA NA NA NA 11735731_a_at PRKRIR protein-kinase, interferon-inducible double stranded RNA dependent inhibitor,Nucleus repressor of (P58 repressor)other rs4494327 chr11:75972484 chr11:75738652-75769528 202956 0.00204 NA NA NA NA NA NA A/HA 11735731_a_at PRKRIR protein-kinase, interferon-inducible double stranded RNA dependent inhibitor,Nucleus repressor of (P58 repressor)other rs2509735 chr11:75950796 chr11:75738652-75769528 181268 0.01968 NA NA NA NA NA NA NA NA NA 11720134_s_at PROS1 protein S (alpha) Extracellular Space other rs6803590 chr3:95133198 chr3:95074572-95175624 0 0.02202 NA NA NA NA NA NA NA NA NA NA 11721905_a_at PSMA4 proteasome (prosome, macropain) subunit, alpha type, 4 Cytoplasm peptidase rs950776 chr15:76713073 chr15:76619802-76628615 84458 0.01136 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11730227_at QRSL1 glutaminyl-tRNA synthase (glutamine-hydrolyzing)-like 1 Cytoplasm enzyme rs2247335 chr6:107099285 chr6:107184134-107222983 84849 0.02355 X NA NA NA NA NA NA NA NA NA 11719784_x_at RPS23 ribosomal protein S23 Cytoplasm translation regulator rs6895884 chr5:81557861 chr5:81604897-81609991 47036 0.02598 NA NA NA NA NA NA NA NA 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other rs10876864 chr12:54687352 chr12:54721953-54724272 34601 0.00000 NA NA HA HA NA NA NA NA NA HA HA NA NA L A/HA 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other rs2069408 chr12:54650588 chr12:54721953-54724272 71365 0.00000 NA NA HA HA NA NA NA NA NA HA HA NA NA NA 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other rs4759229 chr12:54760747 chr12:54721953-54724272 36475 0.00000 NA NA NA NA HA HA NA NA NA A/HA 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other rs7963590 chr12:54681956 chr12:54721953-54724272 39997 0.00715 NA NA NA NA NA NA NA NA NA NA 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other rs17118317 chr12:54806642 chr12:54721953-54724272 82370 0.02598 NA NA NA NA NA NA NA NA NA NA NA 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other rs12580100 chr12:54725476 chr12:54721953-54724272 1204 0.03268 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other rs11171744 chr12:54789394 chr12:54721953-54724272 65122 0.03607 NA NA NA NA NA NA 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other rs7960225 chr12:54851078 chr12:54721953-54724272 126806 0.04237 NA NA HA HA NA NA NA NA HA HA NA NA 11757761_x_at RPS26 ribosomal protein S26 Cytoplasm other rs71078107 chr12:54837612 chr12:54721953-54724272 113340 0.04474 NA NA NA 11718347_a_at S100P S100 calcium binding protein P Cytoplasm other rs3822262 chr4:6748667 chr4:6746467-6749797 0 0.00000 X NA NA NA NA NA NA NA NA NA NA NA NA 11747888_a_at SH3YL1 SH3 domain containing, Ysc84-like 1 (S. cerevisiae) unknown other rs408209 chr2:143279 chr2:208138-254068 64859 0.04830 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11732801_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other rs2318043 chr20:1544473 chr20:1525987-1548689 0 0.00000 NA NA NA NA NA NA NA NA NA NA 11732801_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other rs2243603 chr20:1494911 chr20:1525987-1548689 31076 0.00000 NA NA NA NA NA NA NA NA NA NA NA NA 11732801_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other rs3761269 chr20:1550206 chr20:1525987-1548689 1517 0.00000 NA NA NA NA NA NA NA NA NA NA NA NA 11732801_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other rs2263657 chr20:1468233 chr20:1525987-1548689 57754 0.00001 NA NA NA NA NA NA NA NA NA NA 11732801_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other rs67499412 chr20:1556680 chr20:1525987-1548689 7991 0.00001 NA NA NA NA NA NA NA 11732801_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other rs6074894 chr20:1545050 chr20:1525987-1548689 0 0.00014 NA NA NA NA NA NA NA NA NA 11732801_at SIRPB1 signal-regulatory protein beta 1 Plasma Membrane other rs2263664 chr20:1491409 chr20:1525987-1548689 34578 0.00780 NA NA NA NA NA NA NA NA NA NA NA 11727842_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter rs1059823 chr2:218968088 chr2:218954996-218969860 0 0.00002 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11727842_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter rs2739049 chr2:218972351 chr2:218954996-218969860 2491 0.00117 NA NA NA NA NA NA NA NA NA 11727842_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter rs2695343 chr2:218963667 chr2:218954996-218969860 0 0.00048 X NA NA NA NA NA NA NA NA NA NA 11727842_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter rs4674301 chr2:218951106 chr2:218954996-218969860 3890 0.00022 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11727842_at SLC11A1 solute carrier family 11 (proton-coupled divalent metal ion transporters), memberPlasma 1 Membrane transporter rs2290708 chr2:218960621 chr2:218954996-218969860 0 0.04848 X NA NA NA L NA NA NA NA NA NA L NA NA NA 11741023_a_at SMAD5 SMAD family member 5 Nucleus transcription regulator rs17740150 chr5:135367363 chr5:135496435-135546321 129072 0.04830 NA NA NA NA NA NA NA NA NA NA 11731446_s_at SNCA synuclein, alpha (non A4 component of amyloid precursor) Cytoplasm other rs2736989 chr4:90995280 chr4:90864274-90978470 16810 0.02625 X NA NA NA NA NA NA NA NA NA 11728515_a_at SP140 SP140 nuclear body protein Nucleus transcription regulator rs16827076 chr2:230896066 chr2:230798689-230812033 84033 0.01278 X NA NA NA NA NA NA NA NA NA NA NA 11728515_a_at SP140 SP140 nuclear body protein Nucleus transcription regulator rs11679076 chr2:230892018 chr2:230798689-230812033 79985 0.01419 X NA NA NA NA NA NA 11728515_a_at SP140 SP140 nuclear body protein Nucleus transcription regulator rs11692116 chr2:230928615 chr2:230798689-230812033 116582 0.01419 X NA NA NA NA NA NA NA NA NA NA NA 11728515_a_at SP140 SP140 nuclear body protein Nucleus transcription regulator rs1972707 chr2:230858296 chr2:230798689-230812033 46263 0.01974 X NA NA NA NA NA NA NA NA NA NA NA 11758521_s_at SPIRE1 spire homolog 1 (Drosophila) Cytoplasm other rs2847254 chr18:12717224 chr18:12436512-12647912 69312 0.02298 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11722689_a_at SPTBN1 spectrin, beta, non-erythrocytic 1 Plasma Membrane other rs12615703 chr2:54840646 chr2:54536958-54752086 88560 0.03825 NA NA NA NA NA NA NA NA NA NA NA NA 11723038_at SRSF3 serine/arginine-rich splicing factor 3 Nucleus other rs7747099 chr6:36478232 chr6:36670068-36680221 191836 0.01783 NA NA NA NA L L NA NA NA NA L 11723038_at SRSF3 serine/arginine-rich splicing factor 3 Nucleus other rs236471 chr6:36803639 chr6:36670068-36680221 123418 0.04220 NA NA NA NA NA NA NA NA NA NA 11723038_at SRSF3 serine/arginine-rich splicing factor 3 Nucleus other rs236446 chr6:36830929 chr6:36670068-36680221 150708 0.02803 NA NA NA NA NA NA NA NA NA NA NA NA 11743633_a_at STX2 syntaxin 2 Cytoplasm transporter rs2632601 chr12:129834650 chr12:129840102-129889764 5452 0.04257 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs2857106 chr6:32895548 chr6:32901166-32914525 5618 0.00000 X HA HA HA HA NA HA HA HA HA HA NA 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs241448 chr6:32904662 chr6:32901166-32914525 0 0.00000 X HA HA HA HA HA NA HA HA HA HA HA NA 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs150359 chr6:33030046 chr6:32901166-32914525 115521 0.04235 HA L HA L HA L HA L 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs1894406 chr6:32895034 chr6:32901166-32914525 6132 0.00001 X HA HA HA HA HA L HA HA HA HA HA L 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs4576294 chr6:32906525 chr6:32901166-32914525 0 0.00153 A HA NA HA NA A HA NA HA NA Page 113 of 111 Diabetes

11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs2621367 chr6:32876699 chr6:32901166-32914525 24467 0.00172 X HA A HA NA 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs9469220 chr6:32766288 chr6:32901166-32914525 134878 0.00366 X HA Excluded HA HA L HA HA HA L 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs9273363 chr6:32734250 chr6:32901166-32914525 166916 0.00393 X - - HA HA HA 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs2857103 chr6:32899277 chr6:32901166-32914525 1889 0.00583 X HA HA L HA HA HA HA HA HA 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs1383264 chr6:32847945 chr6:32901166-32914525 53221 0.02396 X HA HA HA NA HA HA HA NA 11741632_a_at TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) Cytoplasm transporter rs2621326 chr6:32891874 chr6:32901166-32914525 9292 0.02962 X HA HA HA HA HA HA HA HA HA HA 11723206_at TCL1A T-cell leukemia/lymphoma 1A Nucleus other rs1748932 chr14:95209837 chr14:95246058-95250286 36221 0.01782 NA NA NA NA NA NA NA NA NA 11744645_a_at TCN2 transcobalamin II Extracellular Space transporter rs4820888 chr22:29347322 chr22:29333070-29353047 0 0.04112 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11725154_a_at TDRD9 tudor domain containing 9 Cytoplasm other rs2236247 chr14:103447840 chr14:103464570-103588755 16730 0.01344 X NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11755219_a_at THBD thrombomodulin Plasma Membrane transmembrane receptor rs844885 chr20:23053180 chr20:22974271-22978301 74879 0.00042 X NA L NA NA NA NA NA NA L NA NA NA 11733111_a_at TLK1 tousled-like kinase 1 Nucleus kinase rs12471930 chr2:171500675 chr2:171555579-171796070 54904 0.00018 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11733111_a_at TLK1 tousled-like kinase 1 Nucleus kinase rs11696064 chr2:171628467 chr2:171555579-171796070 0 0.00228 NA NA NA NA NA NA NA NA NA NA 11733111_a_at TLK1 tousled-like kinase 1 Nucleus kinase rs4667666 chr2:171461770 chr2:171555579-171796070 93809 0.00624 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11733111_a_at TLK1 tousled-like kinase 1 Nucleus kinase rs218311 chr2:171766110 chr2:171555579-171796070 0 0.01006 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11756570_a_at TMEM50B transmembrane protein 50B Plasma Membrane other rs1059293 chr21:33731563 chr21:33743319-33774151 11756 0.00415 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11736523_x_at TNNT1 troponin T type 1 (skeletal, slow) Cytoplasm other rs78105122 chr19:60274513 chr19:60335974-60352418 61461 0.01244 NA NA NA NA NA 11736523_x_at TNNT1 troponin T type 1 (skeletal, slow) Cytoplasm other rs10422978 chr19:60361684 chr19:60335974-60352418 9266 0.00290 NA NA NA NA NA NA NA 11731742_a_at TRDMT1 tRNA aspartic acid methyltransferase 1 Nucleus enzyme rs7924149 chr10:17242840 chr10:17224989-17284076 0 0.00069 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11718280_s_at TRIAP1 TP53 regulated inhibitor of apoptosis 1 Cytoplasm other rs7137953 chr12:119379068 chr12:119366148-119368598 10470 0.01247 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11743175_at TSHZ3 teashirt zinc finger homeobox 3 Nucleus transcription regulator rs12977455 chr19:36648329 chr19:36457693-36532030 116299 0.02437 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11721184_at TSPAN33 tetraspanin 33 Plasma Membrane other rs12667978 chr7:128564697 chr7:128571948-128596768 7251 0.04257 NA NA NA NA NA NA 11728225_at UBE2J1 ubiquitin-conjugating enzyme E2, J1 Cytoplasm enzyme rs854917 chr6:90184109 chr6:90093064-90119338 64771 0.03780 L NA NA NA NA NA NA L NA NA NA NA NA NA 11732665_a_at VSTM1 V-set and transmembrane domain containing 1 unknown other rs612529 chr19:59259065 chr19:59235897-59259019 46 0.00035 NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11747666_a_at WARS tryptophanyl-tRNA synthetase Cytoplasm enzyme rs3783345 chr14:99890289 chr14:99869878-99912433 0 0.00048 X NA NA NA L NA NA NA NA NA NA L NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs9971722 chr12:56594650 chr12:56621712-56637318 27062 0.00000 NA NA NA NA NA NA L NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs10877068 chr12:56763077 chr12:56621712-56637318 125759 0.00003 NA NA NA L NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs66832796 chr12:56708633 chr12:56621712-56637318 71315 0.00025 NA NA NA NA NA NA NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs4553410 chr12:56587478 chr12:56621712-56637318 34234 0.00056 NA NA NA NA NA NA NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs7959475 chr12:56644680 chr12:56621712-56637318 7362 0.00108 NA NA NA NA NA NA NA NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs12368653 chr12:56419523 chr12:56621712-56637318 202189 0.00385 L NA NA Excluded NA NA NA L NA NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs2036451 chr12:56768953 chr12:56621712-56637318 131635 0.00220 NA NA NA NA NA NA NA NA NA L NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs34854770 chr12:56373139 chr12:56621712-56637318 248573 0.01184 NA NA NA NA NA NA NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs11172304 chr12:56384129 chr12:56621712-56637318 237583 0.02043 NA NA NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs238522 chr12:56408832 chr12:56621712-56637318 212880 0.02144 NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs2720178 chr12:56751018 chr12:56621712-56637318 113700 0.04882 NA NA NA NA NA NA NA NA 11743376_at XRCC6BP1 XRCC6 binding protein 1 unknown kinase rs11172462 chr12:56772034 chr12:56621712-56637318 134716 0.02372 NA NA NA NA NA NA NA NA NA NA NA 11732579_s_at ZNF880 zinc finger protein 880 unknown other rs2059818 chr19:57574332 chr19:57564982-57580856 0 0.00000 NA NA NA NA NA NA NA NA NA NA NA NA NA 11732579_s_at ZNF880 zinc finger protein 880 unknown other rs324126 chr19:57577949 chr19:57564982-57580856 0 0.00000 NA NA NA NA NA NA NA NA NA NA NA NA NA NA