.Online Data Supplement

Persistent activation of interlinked Th2-airway epithelial gene networks in sputum-

derived cells from aeroallergen-sensitized symptomatic atopic asthmatics

Authors

Anya C. Jones*, MSc†§, Niamh M. Troy*, BSc†, Elisha White, MHltSci†, Elysia M.

Hollams, PhD†, Alexander M. Gout, PhD†, Kak-Ming Ling, BSc†, Anthony Kicic,

PhD†‡§ll, Peter D Sly, MD DSc**, Patrick G Holt, Dsc FAA†**, Graham L Hall,

PhD†, Anthony Bosco, PhD†

Affiliations

† Telethon Kids Institute, The University of Western Australia;

‡ Department of Respiratory Medicine, Princess Margaret Hospital for Children,

Western Australia;

§ School of Paediatrics and Child Health, The University of Western Australia,

Western Australia; ll Centre for Cell Therapy and Regenerative Medicine, School of Medicine and

Pharmacology, The University of Western Australia, Western Australia;

** Child Health Research Centre, The University of Queensland, Brisbane,

Australia.

Author contributions

* These authors contributed equally to this work. Conception and design of research: AB, GLH, PGH; Acquisition of data: ACJ, NMT, EW, KML, AK; Data analysis: ACJ, NMT, EW, EMH, AMG, KML, AK, AB; Drafting the manuscript for important intellectual content: ACJ, NMT, PGH, AB; Approval of final version of manuscript: ACJ, NMT, EW, EMH, AMG, KML, AK, PGH, GLH, AB Table of Contents

Study population ...... 1 Sputum induction and processing ...... 1 Transcriptome profiling by RNA-Seq ...... 2 RNA-Seq data analysis ...... 2 Immunostaining ...... 4 References ...... 7 Figure E1. Quality assessment of the RNA-Seq data...... 10 Figure E2. Relative log expression (RLE) plot...... 11 Figure E5. Identification of modules associated with HDM sensitization and asthma...... 12 Figure E6. Gene network diagram for module “P”...... 13 Figure E7. Gene network diagram for module “Q”...... 13 Figure E8. Cluster dendrogram to quantify the correlation between modules...... 14 Figure E9. The reconstructed gene networks of the merged modules “P” and “Q”.15 Figure E10. Immunostaining of bronchial epithelial cells of nonatopic controls (n=8) and atopic asthmatics (n=8)...... 16 Table E1. The cellular composition of the sputum...... 17 Table E2. Differentially expressed genes in sputum from HDMS nonwheezers versus nonatopic controls...... 17 Table E3. Differentially expressed genes in sputum from HDMS wheezers versus nonatopic controls...... 20 Table E4. Differentially expressed genes in sputum from HDMS wheezers versus HDMS nonwheezers...... 36 Table E5. Gene ontology biological processes associated with the set of genes that are networked around the hubs...... 52 Table E6. Multiplex literature mining was performed for the genes associated with the four dominant hubs (EGFR, ERBB2, CDH1 and IL13) in the merged module. .. 54 Table E7. Gene ontology cellular components associated with genes from the CDHR3-associated mucociliary clearance module...... 63 Table E8. Characteristics of the study population...... 63

Study population

This study was conducted within the 22-year follow-up of an unselected longitudinal birth cohort recruited in Perth, the Western Australia Pregnancy Cohort (Raine study, (E1)). The study included 2868 infants at birth, and follow-up visits at 1, 2, 3, 6, 8, 10, 14, 17, 18 and 20 years of age (E2-4).

The study participants completed a questionnaire pertaining to respiratory health, they underwent skin prick testing, baseline spirometry and mannitol challenge tests. The participants were required to withhold asthma medications and antihistamines for 72 hours prior to testing, and compliance was verified by questioning on the day of testing.

Participants were classed as having current wheeze if they indicated in the 22-year follow-up questionnaire that they had wheezed in the past 12 months. Current asthma was defined as a positive doctor diagnosis of asthma ever, in addition to both wheeze and asthma medication use in the past 12 months. Atopy was defined by skin prick test wheal ≥3mm for the following allergens: House dust mite Dermatophagoides pteronyssinus; House dust mite

Dermatophagoides farinae; grass mix, grass pollen, dog hair, cat hair, cockroach, mold mix, cow’s milk, egg white.

Sputum induction and processing

Induced sputum was obtained after mannitol inhalation challenge based on the approach first reported by Wood and co-workers (E5). Briefly, an inhaled mannitol challenge test was performed according to the manufacturer’s recommendation (Pharmaxis Ltd, Frenchs

Forest, NSW, Australia). Baseline spirometry was performed (nSpire Health KOKO PFT spirometer) and FEV1 measurements during the challenge test were performed according

E1 current spirometry guidelines (E6). After each inhalation the participant was encouraged to cough and any sputum produced was collected. The challenge test continued until the final dose (635 mg) or if there was a 15% drop in FEV1 from baseline or a 10% drop between doses occurred (indicating a positive test).

Mucus plugs were selected with forceps and disrupted in AIM-V media (Life Technologies) containing 10% (v/v) sputolysin (Calbiochem) and incubated for 10 min at 37C with intermittent vigorous pipetting. The released cells were centrifuged, and a cytospin slide was prepared for differential cell counting. The remaining cells were stabilized in RNAprotect cell reagent (QIAgen) and stored at -80 C for molecular profiling studies.

Transcriptome profiling by RNA-Seq

Total RNA was extracted from sputum employing TRIzol (Ambion) followed by RNeasy

MinElute (QIAgen). The total RNA samples were shipped on dry ice to the Australian

Genome Research Facility for library preparation (TruSeq Stranded mRNA Library Prep Kit,

Illumina) and sequencing (Illumina HiSeq2500, 50-bp single-end reads, v4 chemistry).

Approximately 25 million reads were generated from each sample. The raw sequencing data are available at the NCBI Short Read Archive under accession SRP057350.

RNA-Seq data analysis

The quality of the RNA-Seq data was assessed with the Bioconductor package Rqc (E7) (Fig.

E1). Sequencing reads were aligned to the reference genome (hg19) using Subread (E8).

Reads were counted and summarized at the gene-level using featureCounts. Genes with less than 300 counts in total were removed from the analysis. Differentially expressed genes

E2 were identified employing Empirical analysis of digital gene expression data in R (EdgeR) with False Discovery Rate (FDR) control for multiple testing (E9) (Table E2-4). EdgeR is based on the negative binomial distribution, which is an extension of the Poisson distribution.

EdgeR employs empirical Bayes methods to estimate gene-specific biological variation and moderate these estimates towards a trended mean (E9). The analysis was adjusted for latent variation using the Remove Unwanted Variation (RUV) algorithm (E10) (Fig. E2).

A coexpression network was constructed from the filtered RNA-Seq data (genes with < 300 total counts were removed from the analysis; 14,833 genes remained) employing the weighted gene coexpression network analysis (WGCNA) algorithm (parameters; power = 6,

Pearson correlation, minimum module size = 100, merge cut height = 0.1, pamstage=TRUE)

(E11-12). Prior to network analysis, the count data was transformed using the variance stabilizing transformation algorithm from the DESeq2 package (E13). The modules were analysed by principal component analysis followed by cluster analysis to quantify their overall correlation. Modules associated with clinical traits were identified by plotting the – log10 p-values derived from an edgeR analysis on a module-by-module basis (Figures E5A,

E5B, E5C).

The wiring diagram of modules selected for further study was reconstructed employing experimentally supported molecular relationships from the Ingenuity Systems

KnowledgeBase (E11, E14) (Figures E6, E7). Principal component analysis of the modules suggested that the modules in Fig E6 and E7 were highly correlated (Pearson correlation:

0.897, P-value = 4.441 x 10-15) (Figure E8). We therefore merged them and reconstructed the network (Figure E9).

E3 Immunostaining

Primary bronchial epithelial cells were obtained from 8 healthy nonatopic children and 8 atopic asthmatic children with house dust mite allergy who were undergoing elective surgery for non-respiratory related conditions (Figure E10). Asthma was defined as physician-diagnosed asthma together with documented wheeze by a physician in the previous 12 months. Atopy was determined by a positive radioallergosorbant (RAST) result to a panel of common allergens including; house dust mite, grass pollens, milk, mould, peanut, egg white and animal dander. All children with asthma had mild disease, such that none were being treated with inhaled or oral glucocorticosteroids (Table E8).

Cytospins of ex vivo cells derived from airway sampling were initially created and stained for

CDHR3 and DAPI using methods previously described (E15). Briefly, cells were incubated in a solution of 0.5% Sudan Black B in 70% ethanol to block auto-fluorescence. Cells were then washed in PBS and antigen retrieval performed by incubation with proteinase K. Cells were washed in PBS containing (0.1% v/v) saponin and blocked in 5%BSA, 10%FBS (v/v), 0.1%

Triton X-100 in 1x PBS/saponin solution prior to incubation with polycloncal rabbit anti- human CDHR3 antibody (Novus Biologicals). Cells were washed again in PBS/saponin and incubated with AlexaFluor 488 (Life Technologies). Finally, nucleic acids were stained using

DAPI (Sigma) and signals were then visualized using Nikon Eclipse Ti fluorescent microscope.

All quantifications were performed using ImageJ software as previously described (E16).

E4 References

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Rationale, design and methods for the 22 year follow-up of the western australian pregnancy cohort (raine) study. BMC public health 2015;15:663.

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Klerk N, Holt BJ, Ladyman C, Sadowska A, Rowe J, Loh R, Sly PD, Holt PG. Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling. The Journal of allergy and clinical immunology 2009;124:463-470, 470 e461-

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E4. McKnight CM, Newnham JP, Stanley FJ, Mountain JA, Landau LI, Beilin LJ, Puddey

IB, Pennell CE, Mackey DA. Birth of a cohort--the first 20 years of the raine study. The

Medical journal of Australia 2012;197:608-610.

E5. Wood LG, Powell H, Gibson PG. Mannitol challenge for assessment of airway responsiveness, airway inflammation and inflammatory phenotype in asthma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical

Immunology 2010;40:232-241.

E6. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R,

Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay

R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J, Force AET. Standardisation of spirometry. The European respiratory journal 2005;26:319-338.

E7 E7. Souza W, Carvalho B, (). Rqc: Quality control tool for high-throughput sequencing data., R package version 1.0.4. ed; https://github.com/labbcb/Rqc.

E8. Liao Y, Smyth GK, Shi W. The subread aligner: Fast, accurate and scalable read mapping by seed-and-vote. Nucleic acids research 2013;41:e108.

E9. Anders S, McCarthy DJ, Chen Y, Okoniewski M, Smyth GK, Huber W, Robinson MD.

Count-based differential expression analysis of rna sequencing data using r and bioconductor. Nature protocols 2013;8:1765-1786.

E10. Risso D, Ngai J, Speed TP, Dudoit S. Normalization of rna-seq data using factor analysis of control genes or samples. Nature biotechnology 2014;32:896-902.

E11. Bosco A, Ehteshami S, Panyala S, Martinez FD. Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo. J Allergy Clin Immunol 2012;129:88-94.

E12. Zhang B, Horvath S. A general framework for weighted gene co-expression network analysis. Statistical applications in genetics and molecular biology

2005;4:Article17.

E13. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for rna-seq data with deseq2. Genome biology 2014;15:550.

E14. Kramer A, Green J, Pollard J, Jr., Tugendreich S. Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 2014;30:523-530.

E15. Kicic A, Sutanto EN, Stevens PT, Knight DA, Stick SM. Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma. Am J Respir

Crit Care Med 2006;174:1110-1118.

E16. Burgess A, Vigneron S, Brioudes E, Labbe JC, Lorca T, Castro A. Loss of human greatwall results in g2 arrest and multiple mitotic defects due to deregulation of the

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Enrichr: Interactive and collaborative html5 gene list enrichment analysis tool. BMC bioinformatics 2013;14:128.

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E9 A

B

Figure E1. Quality assessment of the RNA-Seq data. A) Percentage of reads exceeding quality scores; B) Percent GC content for each sequencing cycle. This analysis was based on the R/Bioconductor package Rqc (E7).

E10

Figure E2. Relative log expression (RLE) plot. The data reflect the log-ratios of the read counts of each sample with respect to the median of all samples after normalization with the remove unwanted variation algorithm (RUV) (E10). Grey = nonatopic controls; Black = nonatopic wheezers; Green = HDMS nonwheezers; Red = HDMS wheezers.

E11 A

B

C

Figure E5. Identification of modules associated with HDM sensitization and asthma. Gene network patterns were compared between A) HDMS nonwheezers versus nonatopic controls; B) HDMS wheezers versus nonatopic controls; (C) HDMS wheezers versus HDMS nonwheezers. The data represent the – log10 p-values derived from an edgeR analysis plotted as box plots on a module-by-module basis.

E12

Figure E6. Gene network diagram for module “P”. The gene network was reconstructed employing experimental data from prior studies. Red denotes upregulation, green denotes downregulation. The network was drawn with Ingenuity software (E14).

Figure E7. Gene network diagram for module “Q”. The gene network was reconstructed employing experimental data from prior studies. Red denotes upregulation, green denotes downregulation. The network was drawn with Ingenuity software (E14).

E13

Figure E8. Cluster dendrogram to quantify the correlation between modules. The overall expression of each module was summarized using principal component analysis, and the first principal component for each module (module eigengene) was correlated, subtracted from 1 to define a distance measure, and analyzed by hierarchical clustering. Note that modules “P” and “Q” were highly correlated (Pearson correlation: 0.897, P-value = 4.441 x 10-15); and therefore these modules were merged.

E14

Figure E9. The reconstructed gene networks of the merged modules “P” and “Q”. The gene network was reconstructed employing experimental data from prior studies. Red denotes upregulation, green denotes downregulation. The network was drawn with Ingenuity software (E14).

E15 Figure E10. Immunostaining of bronchial epithelial cells of nonatopic controls (n=8) and atopic asthmatics (n=8).

E16 Table E1. The cellular composition of the sputum.

Sputum composition Nonatopic Nonatopic HDMS HDMS controls wheezers nonwheezers wheezers P Total sputum cells: 3.2x106 4.5x106 2.9x106 2.7x106 total collected [4x106] [8.2x106] [9.3x106] [4.5x106] 0.977 Eosinophils: 9.2x102 b,c 2.2x104 c total collected 0.0 a [0.0] 0.0 b [0.0] [4.7x104] [1.2x105] 0.006 % of sputum cells 0.0 a [0.0] 0.0 a,b [0.0] 0.1 b,c [1.0] 0.9 c [4.0] 0.005 Neutrophils: 1.1x106 7.6x105 1.2x106 1.0x106 total collected [1.9x106] [4.4x106] [5.7x106] [3.6x106] 0.997 % of sputum cells 45.92 [30.0] 52.4 [37.0] 45.1 [51.0] 49.8 [48.0] 0.901 Macrophages: 1.5x106 2.0x106 1.6x106 1.1x106 total collected [2.5x106] [3.2x106] [2.4x106] [1.1x106] 0.666 % of sputum cells 45.3 [31.0] 39.4 [31.0] 49.0 [50.0] 38.1 [34.0] 0.613 Lymphocytes: 1.0x105 6.9x104 4.5x104 5.3x104 total collected [1.5x105] [5.2x105] [1.3x105] [4.9x104] 0.234 % of sputum cells 3.4 a [3.0] 1.6 a,b [3.0] 1.2 b [2.0] 1.0 b [2.0] 0.011 Squamous cells: 8.4x104 2.0x105 1.5x105 1.0x105 total collected [5.1x105] [1.4x106] [4.2x105] [3.2x105] 0.880 % of sputum cells 3.7 [5.0] 3.8 [6.0] 6.4 [9.0] 3.9 [17.0] 0.776 Sputum cell viability (%) 81.4 [11.6] 78.4 [19.5] 80.6 [16.1] 78.6 [10.3] 0.916 Median [interquartile range] is displayed for all continuous measures. P value is derived from analyses comparing the four groups: prevalence values were compared by Chi square analysis; continuous measures were compared by Kruskal Wallis analysis. Where significant differences were observed between the four group groups (P<0.5 in table), each letter denotes sputum groups that do not differ significantly at the 0.05 level after adjusting for multiple comparisons (a vs a = not different; a vs b = significantly different). *Data was missing for 1 participant in each group; percentage represents proportion of available cases positive for outcome. ^Wheezing groups only were compared by Mann Whitney U test. ^^Atopic groups only were compared by Mann Whitney U test.

Table E2. Differentially expressed genes in sputum from HDMS nonwheezers versus nonatopic controls.

Gene Symbol Entrez ID logFC logCPM PValue FDR AATK 9625 1.66105 5.10699 0.00019 0.04282 ADGRG7 84873 -7.03813 -0.54128 0.00001 0.01176 AGER 177 1.45370 3.96743 0.00025 0.04643 ALPL 249 2.23081 7.44977 0.00011 0.03407 AMICA1 120425 0.86097 8.48525 0.00022 0.04642 APOBR 55911 0.85762 7.80889 0.00003 0.02123 ATG16L2 89849 1.30986 7.16068 0.00010 0.03407 C16orf54 283897 1.17219 4.63954 0.00011 0.03407 CCL17 6361 1.94153 2.74645 0.00009 0.03407 CDC42EP2 10435 1.72003 5.79648 0.00017 0.04100 CFP 5199 1.46826 5.73871 0.00013 0.03756 CHIT1 1118 -2.75976 4.99719 0.00000 0.00134 CHRNE 1145 1.57281 3.00777 0.00024 0.04643 CLC 1178 2.50391 2.55598 0.00001 0.01377 CLCA1 1179 4.62221 3.43316 0.00005 0.02656 CORIN 10699 1.61895 -0.84846 0.00010 0.03407 CRABP2 1382 2.40441 1.94911 0.00027 0.04645 CST1 1469 3.81251 3.01298 0.00009 0.03407 CTSK 1513 -0.95093 2.78660 0.00020 0.04282 CYB5D1 124637 1.61983 5.46582 0.00016 0.04002

E17 FAM209B 388799 1.95318 1.26909 0.00019 0.04282 FBXO40 51725 1.92857 -0.43471 0.00008 0.03407 FLJ45513 729220 1.10239 0.62053 0.00017 0.04100 FOLR3 2352 1.55299 3.73045 0.00002 0.01774 GATA1 2623 2.70936 -0.91635 0.00007 0.03125 GATA2 2624 2.83355 0.88787 0.00011 0.03407 GCSAML 148823 2.91786 -0.36323 0.00000 0.01004 GJC2 57165 2.35140 -0.02581 0.00012 0.03407 HDC 3067 3.23123 1.40718 0.00001 0.01004 HSPA6 3310 1.79184 6.45889 0.00011 0.03407 IFI27 3429 -1.28694 6.53998 0.00010 0.03407 IGHG3 3502 -2.86384 4.14009 0.00023 0.04643 IGHV1-3 28473 -3.20096 -1.18144 0.00003 0.02123 IGHV1-8 28472 -3.54161 -0.59637 0.00009 0.03407 IGLV3-19 28797 -3.11590 -0.18014 0.00024 0.04643 IL13 3596 2.92329 -0.30718 0.00001 0.01004 IL1B 3553 1.92891 11.31833 0.00025 0.04643 IL5 3567 4.14863 -0.66217 0.00000 0.00094 KCNK7 10089 1.93801 1.76487 0.00009 0.03407 KLF2 10365 1.37137 7.96403 0.00023 0.04642 LGALS12 85329 1.79659 1.15563 0.00012 0.03407 LINC00671 388387 1.65385 -1.21335 0.00019 0.04282 LOC100132287 100132287 2.04859 -1.11494 0.00006 0.02706 LOC100133331 100133331 1.57674 2.76235 0.00027 0.04650 LOC145474 145474 2.96771 -0.79558 0.00017 0.04100 LOC283588 283588 1.35851 0.30346 0.00021 0.04542 LOC284454 284454 1.83382 7.11940 0.00016 0.04002 LOC388780 388780 2.04959 2.10238 0.00026 0.04645 LOC728392 728392 1.36795 3.95340 0.00005 0.02656 LPAR2 9170 1.33461 5.83993 0.00013 0.03756 LRFN1 57622 1.54052 3.16774 0.00025 0.04643 LST1 7940 0.99619 7.42708 0.00010 0.03407 MAP1LC3A 84557 1.66078 4.85656 0.00022 0.04642 MARC1 64757 1.72543 1.63072 0.00025 0.04643 MEIS3 56917 3.06484 -1.03693 0.00001 0.01004 MIR612 693197 2.70946 1.15221 0.00001 0.01004 MNDA 4332 1.03051 8.63954 0.00025 0.04643 MUC2 4583 3.46659 1.69026 0.00024 0.04643 MYBL1 4603 -0.91663 1.86935 0.00014 0.03844 NFE2 4778 2.10322 4.59471 0.00005 0.02656 NFIL3 4783 1.40089 7.41968 0.00026 0.04645 NTRK1 4914 2.32100 -0.75410 0.00003 0.02126 P2RX1 5023 0.90095 5.07972 0.00001 0.01004 PGLYRP1 8993 2.76314 2.32969 0.00009 0.03407 PLA1A 51365 -1.54372 2.27232 0.00001 0.01239 PRB1 5542 4.76942 -0.84264 0.00001 0.01004 PROK2 60675 2.61947 8.80110 0.00005 0.02656 RAB24 53917 1.46512 6.70555 0.00026 0.04645 RCN3 57333 1.00184 4.19829 0.00019 0.04282 RMRP 6023 1.99520 -0.02313 0.00004 0.02491 RN7SK 125050 2.52097 1.72033 0.00000 0.00134 RNU2-2P 26855 1.53261 1.35607 0.00015 0.03953 RNU4-2 26834 2.84298 -0.13485 0.00001 0.01004 RPPH1 85495 2.57081 1.30676 0.00000 0.00079 S100A12 6283 2.46477 5.40597 0.00013 0.03756

E18 SAP25 100316904 1.22197 3.75897 0.00011 0.03407 SCARNA10 692148 2.74737 -0.79403 0.00001 0.01004 SH2B2 10603 1.19242 5.23659 0.00015 0.04002 SLC22A14 9389 2.54299 -0.12214 0.00011 0.03407 SLC4A10 57282 -1.58193 -0.08990 0.00002 0.01774 SLED1 643036 2.25110 2.08625 0.00009 0.03407 SNORA73B 26768 1.71425 -0.47930 0.00003 0.02123 SPATA2L 124044 1.10571 4.54651 0.00016 0.04002 TCAP 8557 1.64158 -0.17603 0.00021 0.04542 TEK 7010 2.49691 -1.20809 0.00002 0.01398 THBS1 7057 1.70520 8.50201 0.00003 0.02123 TMEM88 92162 1.87195 4.28950 0.00003 0.02174 TMEM91 641649 1.06148 3.83444 0.00005 0.02656 TSPAN2 10100 2.35842 2.29619 0.00004 0.02491 ZNF252P-AS1 286103 1.96655 -0.88830 0.00029 0.04970 ZNF467 168544 1.97908 3.65964 0.00019 0.04282

E19 Table E3. Differentially expressed genes in sputum from HDMS wheezers versus nonatopic controls.

Gene Symbol Entrez ID logFC logCPM PValue FDR AADAC 13 5.17254 -1.54772 0.00000 0.00000 ABCA10 10349 1.48376 -1.43104 0.00035 0.00840 ABCA13 154664 3.69190 2.80247 0.00000 0.00000 ABCC6 368 1.70470 -0.39958 0.00073 0.01598 ABHD12B 145447 1.26789 0.06031 0.00017 0.00450 ACBD7 414149 2.64195 -1.36439 0.00000 0.00001 ADAMTSL3 57188 4.92291 -1.44907 0.00000 0.00001 ADCY2 108 3.38525 -1.33464 0.00000 0.00001 ADCY6 112 1.10509 1.22601 0.00155 0.03092 ADGB 79747 2.82885 -0.26822 0.00014 0.00372 ADGRA3 166647 1.34997 -0.64074 0.00087 0.01865 ADGRF5 221395 3.47375 -1.41043 0.00000 0.00000 ADGRG1 9289 1.94175 2.82311 0.00015 0.00402 ADGRV1 84059 2.28580 -0.57164 0.00001 0.00035 ADH1C 126 4.19715 2.30533 0.00000 0.00009 ADH7 131 4.43706 1.58974 0.00000 0.00001 ADRA2A 150 5.60374 -0.17986 0.00000 0.00000 ADRB1 153 1.94044 -1.41522 0.00114 0.02367 ADSSL1 122622 0.77274 0.45574 0.00106 0.02223 AGBL2 79841 2.93312 0.72962 0.00000 0.00000 AGR2 10551 4.62811 4.67229 0.00000 0.00000 AGR3 155465 4.90053 1.17872 0.00000 0.00000 AK7 122481 5.11497 0.30564 0.00000 0.00000 AK8 158067 1.47086 0.26219 0.00114 0.02374 AKAP14 158798 4.79703 -0.60615 0.00000 0.00000 AKAP6 9472 1.92727 -0.06240 0.00002 0.00051 AKR1C1 1645 1.15582 3.29769 0.00196 0.03774 AKT1S1 84335 0.83080 4.96030 0.00133 0.02706 ALDH1L1 10840 2.09367 0.31046 0.00117 0.02413 ALDH3A1 218 2.11824 4.06667 0.00091 0.01935 ALOX15 246 6.53983 5.40730 0.00000 0.00000 ALS2CR12 130540 1.06851 -0.04034 0.00165 0.03253 ALYREF 10189 0.44249 4.74395 0.00226 0.04251 AMOT 154796 2.20911 0.92148 0.00000 0.00000 ANK3 288 1.26543 1.45130 0.00016 0.00432 ANKK1 255239 1.64719 -1.22336 0.00002 0.00068 ANKRD45 339416 4.93856 -0.87217 0.00000 0.00000 ANKRD65 441869 2.43988 0.21215 0.00001 0.00045 ANKRD66 100287718 3.35684 -1.02946 0.00000 0.00000 ANKUB1 389161 4.09484 -0.30938 0.00000 0.00000 ANO1 55107 2.36304 0.24012 0.00080 0.01726 ANO7 50636 1.07378 -0.89370 0.00146 0.02944 AP1M2 10053 2.33716 0.98721 0.00006 0.00174 APOBEC4 403314 4.89182 -0.36724 0.00000 0.00000 APOD 347 3.53801 -0.92482 0.00001 0.00024 AQP3 360 0.88726 6.02543 0.00124 0.02560 ARFGEF3 57221 3.30082 1.74192 0.00000 0.00000 ARFIP2 23647 0.35982 4.19288 0.00255 0.04696 ARHGAP39 80728 1.56766 0.73945 0.00000 0.00017 ARHGAP40 343578 2.43107 0.18297 0.00133 0.02714 ARHGAP42 143872 1.97570 -0.96978 0.00028 0.00685 ARMC3 219681 4.62100 0.82775 0.00000 0.00000

E20 ARMC4 55130 5.18160 0.01078 0.00000 0.00000 ATF5 22809 0.83881 5.96384 0.00143 0.02881 ATG101 60673 0.50714 4.62616 0.00029 0.00714 ATP13A5 344905 3.66328 -0.90289 0.00009 0.00241 ATP2C2 9914 2.42755 2.04503 0.00002 0.00073 ATP5I 521 0.46897 4.96942 0.00168 0.03303 ATP7B 540 2.17179 0.69746 0.00000 0.00018 AUTS2 26053 1.05927 2.05885 0.00266 0.04868 B3GNT6 192134 2.36855 -0.52509 0.00073 0.01596 B4GALNT3 283358 2.47054 0.61227 0.00001 0.00027 B9D1 27077 1.84421 0.11357 0.00000 0.00001 BAIAP3 8938 1.85438 2.00738 0.00055 0.01250 BATF3 55509 1.05071 2.62011 0.00007 0.00209 BCAS1 8537 1.93046 2.50139 0.00085 0.01824 BDKRB2 624 1.96584 -0.03202 0.00099 0.02099 BEND7 222389 2.05114 -1.17690 0.00092 0.01964 BEST4 266675 2.30336 0.04578 0.00000 0.00012 BMP3 651 3.23934 -0.74909 0.00003 0.00092 BMPR1B 658 2.93305 -0.96659 0.00003 0.00082 BPIFB1 92747 6.27042 7.33747 0.00000 0.00000 BSPRY 54836 2.25550 0.03969 0.00007 0.00211 C10orf107 219621 4.65663 -0.29696 0.00000 0.00000 C11orf16 56673 3.90498 -0.05526 0.00000 0.00000 C11orf52 91894 3.27508 -0.90904 0.00000 0.00001 C11orf70 85016 5.39746 -0.05988 0.00000 0.00000 C11orf88 399949 3.85644 0.36227 0.00000 0.00000 C11orf97 643037 4.08643 -1.37620 0.00000 0.00006 C14orf37 145407 1.14069 -1.23100 0.00212 0.04030 C15orf26 161502 3.54156 -0.74851 0.00000 0.00000 C16orf71 146562 3.29017 -0.44268 0.00000 0.00000 C16orf89 146556 3.53795 -1.00357 0.00000 0.00001 C16orf93 90835 1.04701 -0.47101 0.00250 0.04613 C1orf110 339512 4.34455 0.10907 0.00000 0.00000 C1orf141 400757 4.79316 -1.44916 0.00000 0.00000 C1orf158 93190 4.03920 -1.04087 0.00000 0.00001 C1orf168 199920 3.36761 -0.94784 0.00000 0.00000 C1orf189 388701 1.98306 -0.89289 0.00046 0.01075 C1orf194 127003 4.00076 0.51938 0.00000 0.00000 C1orf210 149466 2.42396 -1.42674 0.00057 0.01300 C1orf228 339541 0.85486 2.70676 0.00029 0.00712 C1orf87 127795 5.28619 -0.06751 0.00000 0.00000 C20orf85 128602 4.33474 1.88592 0.00000 0.00000 C21orf58 54058 1.71140 0.64586 0.00001 0.00032 C22orf15 150248 3.38350 -0.71199 0.00000 0.00000 C2orf40 84417 4.22291 -0.25929 0.00000 0.00000 C2orf81 388963 0.94203 0.99849 0.00070 0.01536 C3orf52 79669 1.69462 -0.23118 0.00186 0.03598 C3orf67 200844 1.39320 -1.08505 0.00107 0.02235 C4orf47 441054 3.25452 -1.11165 0.00000 0.00000 C5orf49 134121 4.28921 0.24224 0.00000 0.00000 C6orf118 168090 5.26208 -0.28609 0.00000 0.00000 C6orf165 154313 4.54349 0.19129 0.00000 0.00000 C7orf57 136288 2.34282 0.20087 0.00000 0.00000 C8orf4 56892 3.23543 1.21940 0.00011 0.00309 C9orf116 138162 2.88352 0.39155 0.00000 0.00000

E21 C9orf117 286207 2.56975 1.43025 0.00000 0.00000 C9orf135 138255 5.04625 -0.21445 0.00000 0.00000 C9orf152 401546 3.20268 0.06120 0.00000 0.00008 C9orf171 389799 3.96851 -0.65288 0.00000 0.00000 C9orf24 84688 3.30595 1.14302 0.00000 0.00000 C9orf9 11092 1.23521 0.57568 0.00002 0.00050 CACFD1 11094 0.53240 2.26608 0.00238 0.04427 CACNA1D 776 1.37081 -0.31088 0.00047 0.01078 CACNG6 59285 4.96137 -0.63144 0.00000 0.00000 CALCRL 10203 1.07988 2.27537 0.00176 0.03435 CAMK1 8536 0.87699 2.84323 0.00090 0.01924 CAP2 10486 4.44480 -0.81571 0.00000 0.00000 CAPN13 92291 3.15799 0.44552 0.00008 0.00218 CAPN8 388743 3.47971 -0.37717 0.00000 0.00000 CAPN9 10753 4.40062 -0.44140 0.00000 0.00002 CAPS 828 2.45677 4.11278 0.00000 0.00000 CAPS2 84698 1.71374 -0.37893 0.00002 0.00054 CAPSL 133690 4.94686 0.61992 0.00000 0.00000 CASC1 55259 3.98678 0.18127 0.00000 0.00000 CASC2 255082 2.34061 -0.90634 0.00000 0.00001 CATSPERD 257062 3.31277 -1.41907 0.00000 0.00000 CC2D2A 57545 0.80817 3.01303 0.00059 0.01333 CCDC103 388389 1.08871 0.09798 0.00083 0.01796 CCDC108 255101 4.33765 0.74404 0.00000 0.00000 CCDC113 29070 2.64571 1.45200 0.00000 0.00000 CCDC114 93233 3.64452 1.16591 0.00000 0.00000 CCDC13 152206 0.77765 1.07386 0.00070 0.01536 CCDC146 57639 1.21539 2.93011 0.00005 0.00159 CCDC151 115948 1.86501 0.21657 0.00000 0.00010 CCDC153 283152 0.79966 1.19141 0.00147 0.02947 CCDC157 550631 1.06838 1.00104 0.00057 0.01300 CCDC17 149483 2.09900 3.16367 0.00000 0.00000 CCDC170 80129 1.43212 2.66412 0.00000 0.00002 CCDC173 129881 3.93245 -0.85957 0.00000 0.00000 CCDC176 80127 1.94664 1.43542 0.00000 0.00000 CCDC181 57821 2.51510 -0.69866 0.00000 0.00000 CCDC30 728621 0.90738 0.24102 0.00247 0.04562 CCDC33 80125 4.20859 -0.46857 0.00000 0.00002 CCDC34 91057 0.79131 0.34003 0.00262 0.04807 CCDC37 348807 3.55508 0.56838 0.00000 0.00000 CCDC39 339829 1.12904 1.33479 0.00008 0.00222 CCDC40 55036 1.34069 1.64979 0.00008 0.00217 CCDC42B 387885 3.04344 0.14348 0.00000 0.00000 CCDC60 160777 4.06351 -0.68457 0.00000 0.00002 CCDC65 85478 2.44419 0.77110 0.00000 0.00001 CCDC74A 90557 2.99188 -0.47447 0.00000 0.00002 CCDC74B 91409 3.47442 -1.37370 0.00000 0.00000 CCDC78 124093 2.06297 2.11131 0.00000 0.00002 CCDC80 151887 2.43929 0.10875 0.00029 0.00715 CCDC81 60494 2.43390 0.22511 0.00000 0.00001 CCDC89 220388 4.40617 -1.11768 0.00000 0.00000 CCDC96 257236 0.88118 1.40221 0.00013 0.00353 CCL17 6361 3.52445 2.74645 0.00000 0.00000 CCL22 6367 1.10448 5.63922 0.00114 0.02367 CCL26 10344 4.50358 -0.57168 0.00000 0.00000

E22 CCNA1 8900 1.49826 0.55346 0.00018 0.00460 CCNO 10309 3.50501 -0.51631 0.00000 0.00000 CD164L2 388611 3.83297 -0.38927 0.00000 0.00001 CD1B 910 2.12343 1.68466 0.00003 0.00095 CD1C 911 1.24446 4.19473 0.00113 0.02359 CD1E 913 1.65987 3.10751 0.00008 0.00233 CD207 50489 1.59030 2.87301 0.00039 0.00914 CD24 100133941 2.65529 4.83242 0.00002 0.00050 CDC20B 166979 5.31571 -0.15087 0.00000 0.00000 CDC42EP4 23580 0.57614 4.05918 0.00058 0.01312 CDC42EP5 148170 2.26541 1.37094 0.00080 0.01727 CDH1 999 2.47077 3.09516 0.00001 0.00038 CDH26 60437 3.62071 2.55003 0.00000 0.00000 CDHR3 222256 4.68944 2.47440 0.00000 0.00000 CDHR4 389118 4.35225 1.02589 0.00000 0.00000 CDKL2 8999 1.65878 -1.44165 0.00011 0.00299 CDON 50937 1.80502 -1.19346 0.00015 0.00396 CEBPE 1053 1.71483 0.66164 0.00000 0.00001 CEL 1056 1.25104 -1.45725 0.00166 0.03272 CEP126 57562 1.72318 0.87028 0.00000 0.00009 CETN2 1069 0.57490 4.64628 0.00060 0.01345 CFAP126 257177 1.50743 1.28318 0.00000 0.00004 CFAP221 200373 4.80258 0.16289 0.00000 0.00000 CFAP43 80217 4.40944 1.90812 0.00000 0.00000 CFAP44 55779 1.22416 2.42167 0.00005 0.00153 CFAP45 25790 2.60286 2.24416 0.00001 0.00033 CFAP46 54777 3.69114 -0.51184 0.00000 0.00003 CFAP52 146845 4.38168 0.53648 0.00000 0.00000 CFAP53 220136 3.03915 0.13038 0.00000 0.00000 CFAP57 149465 4.70263 -1.01566 0.00000 0.00000 CFAP61 26074 2.24689 -0.41652 0.00000 0.00002 CFAP69 79846 2.84281 0.06391 0.00000 0.00000 CFAP70 118491 2.16081 0.89080 0.00000 0.00001 CFAP74 85452 4.63981 -1.28926 0.00000 0.00000 CFAP99 402160 3.51470 -1.18414 0.00000 0.00001 CFI 3426 1.80371 -0.30192 0.00069 0.01516 CFTR 1080 3.35969 -0.55887 0.00000 0.00012 CGN 57530 2.34272 2.14491 0.00007 0.00209 CHIT1 1118 -2.79470 4.99719 0.00002 0.00056 CHL1 10752 2.35536 0.37797 0.00087 0.01865 CHN2 1124 0.56240 3.31597 0.00121 0.02488 CHP2 63928 3.10396 -1.30118 0.00003 0.00080 CHST6 4166 5.35988 1.49209 0.00000 0.00000 CHST9 83539 4.00973 0.86974 0.00000 0.00000 CIB1 10519 0.54239 6.98598 0.00035 0.00838 CITED4 163732 1.20302 0.11070 0.00198 0.03801 CLC 1178 4.21030 2.55598 0.00000 0.00000 CLCA1 1179 10.95384 3.43316 0.00000 0.00000 CLCA2 9635 3.42372 0.74797 0.00000 0.00009 CLDN10 9071 3.11798 -0.58234 0.00012 0.00328 CLDN3 1365 3.43304 0.96824 0.00000 0.00000 CLEC4F 165530 1.88654 0.87099 0.00003 0.00099 CLEC4G 339390 2.19173 -0.93304 0.00006 0.00161 CLIC6 54102 3.99763 2.12700 0.00000 0.00000 CLU 1191 3.06301 3.15460 0.00000 0.00000

E23 CMTM4 146223 2.11167 1.86909 0.00000 0.00000 CMYA5 202333 3.13373 0.56709 0.00000 0.00000 CNGA4 1262 2.95207 -0.83757 0.00000 0.00000 COBL 23242 2.84630 0.11588 0.00000 0.00014 COL21A1 81578 3.76045 -0.97744 0.00000 0.00014 COL28A1 340267 3.21116 -1.16060 0.00000 0.00012 COL4A5 1287 2.99611 -0.96997 0.00022 0.00556 COLCA1 399948 4.61792 0.43082 0.00000 0.00000 COLCA2 120376 4.32396 -1.57003 0.00000 0.00008 CP 1356 2.51344 2.08888 0.00003 0.00102 CPA3 1359 4.02658 1.91325 0.00000 0.00000 CREB3L1 90993 4.26630 1.14103 0.00000 0.00000 CRISPLD1 83690 2.83721 -1.44548 0.00000 0.00000 CRNDE 643911 1.92618 0.23097 0.00000 0.00000 CROCC 9696 0.63461 2.90534 0.00148 0.02967 CSRP2 1466 2.17546 -0.99315 0.00015 0.00403 CST1 1469 7.62645 3.01298 0.00000 0.00000 CST2 1470 3.32776 -0.18703 0.00043 0.01008 CST4 1472 5.90725 -0.72061 0.00000 0.00002 CTGF 1490 1.86132 3.50350 0.00179 0.03489 CTNNAL1 8727 1.11006 2.17456 0.00018 0.00483 CTSK 1513 -0.94239 2.78660 0.00125 0.02569 CTTN 2017 1.54124 2.74528 0.00086 0.01848 CTXN1 404217 3.39636 -0.45719 0.00000 0.00000 CX3CL1 6376 2.20729 -0.34489 0.00024 0.00618 CXCL17 284340 2.33407 3.70186 0.00041 0.00962 CYB561 1534 0.59207 3.67402 0.00041 0.00961 CYP2A13 1553 2.89478 -1.41681 0.00100 0.02114 CYP2A6 1548 2.26334 -0.74083 0.00055 0.01250 CYP2B7P 1556 2.48990 1.61846 0.00002 0.00064 CYP2C18 1562 2.38160 -1.09051 0.00182 0.03543 CYP2F1 1572 2.62975 0.88142 0.00016 0.00419 CYP2J2 1573 3.14272 -0.80530 0.00001 0.00038 CYP4B1 1580 4.23370 2.61711 0.00000 0.00001 DACH1 1602 1.93024 -0.41033 0.00026 0.00658 DAW1 164781 4.47948 -0.14511 0.00000 0.00000 DCBLD2 131566 0.63469 2.27494 0.00136 0.02768 DCDC2B 149069 1.04305 0.93567 0.00032 0.00774 DCDC5 100506627 3.33058 -1.36558 0.00000 0.00000 DDR1 780 1.93773 3.62324 0.00000 0.00012 DEGS2 123099 2.36481 -0.63134 0.00001 0.00026 DENND6B 414918 0.95167 1.62971 0.00008 0.00233 DLEC1 9940 1.72626 2.78038 0.00001 0.00023 DLG3 1741 1.46356 1.49058 0.00179 0.03489 DMTN 2039 1.67057 -0.06890 0.00002 0.00064 DNAAF1 123872 3.41370 2.29543 0.00000 0.00000 DNAAF3 352909 3.78444 0.38279 0.00000 0.00000 DNAH10 196385 3.55100 1.39591 0.00000 0.00000 DNAH11 8701 3.80514 0.95601 0.00000 0.00000 DNAH12 201625 4.00064 1.83912 0.00000 0.00000 DNAH2 146754 3.34834 1.24030 0.00000 0.00000 DNAH3 55567 3.77178 1.86750 0.00000 0.00000 DNAH5 1767 4.45831 2.22698 0.00000 0.00000 DNAH6 1768 3.71480 0.89946 0.00000 0.00000 DNAH7 56171 3.00798 0.80324 0.00000 0.00000

E24 DNAH9 1770 4.64205 1.75783 0.00000 0.00000 DNAI1 27019 4.34479 0.96294 0.00000 0.00000 DNAI2 64446 3.68313 0.60499 0.00000 0.00000 DNAJB13 374407 1.43495 0.27397 0.00012 0.00328 DNAJC12 56521 1.35238 -1.30346 0.00209 0.03998 DNALI1 7802 2.60690 1.68768 0.00000 0.00000 DNASE1L3 1776 2.62969 2.56850 0.00000 0.00001 DNER 92737 4.24116 -0.95511 0.00000 0.00000 DOC2A 8448 1.53581 -0.96394 0.00003 0.00104 DPCD 25911 0.86835 1.66017 0.00012 0.00328 DPY19L2P2 349152 2.26930 -1.15009 0.00008 0.00233 DQX1 165545 1.43415 -1.37687 0.00088 0.01878 DRC1 92749 4.48861 1.05393 0.00000 0.00000 DSG2 1829 1.46649 1.49881 0.00036 0.00860 DTHD1 401124 4.10164 1.04574 0.00000 0.00000 DUOX1 53905 2.09342 2.69918 0.00019 0.00491 DYDC2 84332 5.23342 -0.19877 0.00000 0.00000 DYNLRB2 83657 3.77616 -0.38763 0.00000 0.00000 DYNLT1 6993 0.60776 5.98380 0.00145 0.02936 DZIP1 22873 3.25174 -1.20135 0.00000 0.00005 ECT2L 345930 3.13742 0.78362 0.00000 0.00000 EFCAB1 79645 3.84277 1.06329 0.00000 0.00000 EFCAB10 100130771 2.98375 -1.47589 0.00000 0.00000 EFCAB12 90288 1.68775 0.39348 0.00018 0.00472 EFCAB2 84288 0.62363 2.30361 0.00155 0.03094 EFCAB6 64800 2.06636 -0.22621 0.00000 0.00004 EFEMP1 2202 3.67690 -0.04456 0.00000 0.00010 EFHB 151651 3.87922 0.18714 0.00000 0.00000 EFHC1 114327 1.35868 3.32792 0.00000 0.00012 EFHC2 80258 3.04468 0.76469 0.00000 0.00001 EML1 2009 2.28850 -0.25768 0.00003 0.00097 ENAH 55740 3.16763 1.11261 0.00000 0.00000 ENHO 375704 1.96614 -1.22490 0.00009 0.00240 ENKUR 219670 4.71858 0.72256 0.00000 0.00000 ENO4 387712 0.84864 0.04940 0.00212 0.04030 ENPP1 5167 2.24274 -0.50685 0.00001 0.00023 ENTPD3 956 2.09477 -0.84432 0.00059 0.01329 EPB41L4B 54566 4.24529 0.92841 0.00000 0.00000 EPCAM 4072 3.96764 1.13868 0.00000 0.00000 EPHX2 2053 1.61583 -0.76068 0.00058 0.01314 EPPIN 57119 3.57312 -1.43253 0.00001 0.00026 ERBB2 2064 1.69504 2.33867 0.00001 0.00038 ERBB4 2066 5.16083 -0.71719 0.00000 0.00002 ERICH3 127254 4.71173 1.72467 0.00000 0.00000 ERICH5 203111 3.32350 -0.88368 0.00000 0.00000 ERN2 10595 3.20797 1.34204 0.00001 0.00027 ESP33 100188917 3.05767 -0.22029 0.00002 0.00054 ESPN 83715 1.05964 -0.21184 0.00213 0.04053 ESRRG 2104 2.90727 -1.36134 0.00003 0.00079 EYA1 2138 3.83921 -0.62120 0.00000 0.00001 EYA4 2070 3.06313 -0.26549 0.00001 0.00043 F13A1 2162 1.73290 4.29137 0.00020 0.00510 FA2H 79152 2.67369 0.20636 0.00019 0.00493 FAAH2 158584 1.62963 -0.59898 0.00166 0.03272 FABP6 2172 2.85715 -0.60128 0.00001 0.00034

E25 FAIM3 9214 -0.71935 4.43535 0.00160 0.03177 FAM149A 25854 1.89043 0.00312 0.00001 0.00021 FAM161A 84140 1.13115 -0.28252 0.00026 0.00657 FAM166B 730112 3.50458 0.20046 0.00000 0.00000 FAM171A1 221061 1.85660 -0.96832 0.00025 0.00639 FAM174B 400451 1.77928 0.39782 0.00002 0.00050 FAM179A 165186 2.27961 1.58074 0.00000 0.00002 FAM183A 440585 3.30301 0.41080 0.00000 0.00000 FAM184A 79632 1.45556 -0.66753 0.00026 0.00649 FAM188B 84182 1.46079 0.16186 0.00000 0.00012 FAM216B 144809 4.45499 2.01312 0.00000 0.00000 FAM227A 646851 3.04639 0.03738 0.00000 0.00000 FAM229B 619208 1.76126 0.69056 0.00000 0.00001 FAM47E 100129583 1.24396 0.25058 0.00089 0.01901 FAM81A 145773 1.55941 -0.90996 0.00078 0.01696 FAM81B 153643 4.14099 0.32300 0.00000 0.00000 FAM83E 54854 2.78504 0.46277 0.00002 0.00062 FAM83F 113828 2.07914 -1.07989 0.00158 0.03134 FAM83H-AS1 100128338 2.85746 -0.74514 0.00000 0.00000 FAM92B 339145 4.82219 0.92434 0.00000 0.00000 FAM95C 100289137 3.01394 -1.36407 0.00000 0.00001 FANK1 92565 2.72793 0.91758 0.00000 0.00000 FBXO15 201456 2.29605 -0.16702 0.00000 0.00005 FBXO36 130888 1.31487 0.41565 0.00005 0.00160 FCGBP 8857 2.55655 4.83826 0.00005 0.00134 FER1L4 80307 1.49323 0.31674 0.00086 0.01855 FER1L6 654463 2.43918 1.75093 0.00007 0.00212 FETUB 26998 6.59966 -1.41739 0.00000 0.00000 FGF14 2259 5.06868 -1.39321 0.00000 0.00000 FGFR2 2263 2.07673 0.12220 0.00037 0.00863 FILIP1 27145 4.05547 -1.39865 0.00000 0.00000 FMOD 2331 1.90734 -1.00578 0.00002 0.00058 FOXA1 3169 2.54320 2.18689 0.00006 0.00184 FOXA3 3171 5.75493 -1.06352 0.00000 0.00000 FOXJ1 2302 4.59650 2.11313 0.00000 0.00000 FRMPD2 143162 4.40247 -0.93494 0.00000 0.00002 FSIP1 161835 1.12523 -0.47479 0.00147 0.02957 FXYD3 5349 3.38884 2.81887 0.00000 0.00002 FZD3 7976 1.63728 -1.27094 0.00034 0.00807 FZD6 8323 2.13071 0.88489 0.00000 0.00006 GALNT18 374378 3.74269 -1.19460 0.00001 0.00023 GAS2L2 246176 4.00899 0.25830 0.00000 0.00000 GATA1 2623 4.10613 -0.91635 0.00000 0.00000 GATA2 2624 3.16679 0.88787 0.00006 0.00170 GCSAML 148823 2.57203 -0.36323 0.00011 0.00299 GEMIN8P4 492303 0.88737 -0.55638 0.00180 0.03502 GIPR 2696 2.12084 0.34496 0.00000 0.00010 GLB1L2 89944 2.94640 -0.32757 0.00000 0.00000 GMNC 647309 2.48215 -1.37355 0.00001 0.00038 GNAI1 2770 1.51858 1.18232 0.00056 0.01283 GOLM1 51280 0.98571 4.69804 0.00038 0.00896 GPRC5C 55890 1.43190 0.50767 0.00193 0.03723 GPX2 2877 2.71696 0.62426 0.00010 0.00284 GPX8 493869 1.49142 -0.86504 0.00064 0.01424 GRAMD2 196996 2.94256 -1.50703 0.00004 0.00120

E26 GRHL2 79977 3.52669 0.15379 0.00000 0.00002 GRIN3B 116444 1.16481 -0.04192 0.00164 0.03245 GSTA1 2938 3.47417 1.44222 0.00000 0.00001 GSTA2 2939 3.79935 0.36670 0.00000 0.00001 HDC 3067 4.09992 1.40718 0.00000 0.00001 HERC5 51191 0.94054 5.71847 0.00227 0.04267 HHLA2 11148 2.82886 -0.88983 0.00001 0.00019 HID1 283987 2.89219 0.35261 0.00000 0.00014 HMGB3 3149 0.57802 2.60965 0.00096 0.02024 HMGCS2 3158 4.05003 -1.00959 0.00000 0.00016 HOOK1 51361 1.99792 1.29045 0.00005 0.00147 HRASLS2 54979 3.36920 -0.98353 0.00000 0.00001 HRASLS5 117245 2.29784 -0.38921 0.00000 0.00001 HRH4 59340 1.75660 0.25158 0.00014 0.00388 HS6ST2 90161 2.43483 -1.45802 0.00027 0.00671 HSD17B13 345275 3.98975 0.61765 0.00000 0.00000 HSPA4L 22824 2.04298 -0.58576 0.00000 0.00018 HYAL1 3373 1.42455 -1.17263 0.00064 0.01419 HYAL3 8372 0.64121 0.19480 0.00259 0.04755 HYDIN 54768 3.89509 1.45214 0.00000 0.00000 IFI35 3430 0.71675 5.74218 0.00126 0.02583 IFT22 64792 0.81618 2.11487 0.00103 0.02159 IFT81 28981 1.09673 1.29424 0.00004 0.00131 IGFBP5 3488 4.71785 0.77678 0.00000 0.00000 IGFBP7 3490 1.54613 2.03145 0.00000 0.00009 IGHD 3495 -2.92338 2.31099 0.00198 0.03797 IGLON5 402665 1.65951 1.76068 0.00050 0.01154 IGSF3 3321 1.23194 -0.16134 0.00073 0.01596 IL13 3596 3.02514 -0.30718 0.00002 0.00069 IL1RL1 9173 3.28371 1.77819 0.00000 0.00017 IL20RA 53832 3.50698 -0.98573 0.00001 0.00027 IL33 90865 2.59791 -0.59470 0.00093 0.01975 IL5 3567 5.29559 -0.66217 0.00000 0.00000 IL5RA 3568 3.78085 -1.18566 0.00000 0.00001 ILDR1 286676 1.20911 -0.20548 0.00081 0.01750 INHBB 3625 1.90043 -0.50471 0.00026 0.00657 IQCA1 79781 1.76356 0.17311 0.00001 0.00040 IQCD 115811 2.42504 -0.05088 0.00001 0.00044 IQCH 64799 2.64217 -0.96483 0.00000 0.00000 IQUB 154865 4.27915 -0.85679 0.00000 0.00000 IRX3 79191 3.51086 -0.36518 0.00000 0.00002 IRX5 10265 2.94668 -1.35533 0.00001 0.00045 ISG15 9636 1.68756 7.02586 0.00024 0.00604 KCNH3 23416 1.94098 0.36262 0.00038 0.00898 KCNJ16 3773 5.67596 -0.21957 0.00000 0.00000 KCNRG 283518 1.94724 -0.54207 0.00000 0.00002 KCTD1 284252 1.25994 0.46788 0.00005 0.00160 KCTD14 65987 1.75477 -1.30541 0.00048 0.01100 KIAA0895 23366 2.45642 -0.43425 0.00000 0.00004 KIAA1211L 343990 1.12973 1.90461 0.00003 0.00100 KIAA1217 56243 1.79531 1.61333 0.00167 0.03285 KIAA1456 57604 1.08696 -0.19746 0.00154 0.03083 KIAA1549 57670 3.90024 -0.61230 0.00000 0.00000 KIAA1671 85379 1.92892 1.68709 0.00001 0.00028 KIF19 124602 3.80804 0.05216 0.00000 0.00000

E27 KIF21A 55605 2.18874 1.76665 0.00000 0.00002 KIF9 64147 0.87877 1.18742 0.00003 0.00101 KIT 3815 1.41814 1.02212 0.00102 0.02156 KLF3-AS1 79667 1.10637 -1.49414 0.00249 0.04584 KLHDC7A 127707 5.02876 -0.61259 0.00000 0.00000 KLHDC9 126823 1.43732 -0.67573 0.00004 0.00125 KLHL13 90293 3.03092 -1.42398 0.00000 0.00010 KNDC1 85442 3.00951 0.03493 0.00000 0.00001 KRT8 3856 2.29696 3.53816 0.00008 0.00232 LAMC2 3918 1.54733 2.46644 0.00229 0.04288 LARP6 55323 1.53294 -0.76695 0.00011 0.00301 LAYN 143903 1.49503 -0.25936 0.00030 0.00724 LCA5 167691 1.81138 0.49667 0.00001 0.00042 LCA5L 150082 1.67249 -0.66825 0.00003 0.00096 LDLRAD1 388633 4.83233 -0.35331 0.00000 0.00000 LEKR1 389170 1.36625 -0.88017 0.00007 0.00213 LGALS12 85329 3.36003 1.15563 0.00000 0.00000 LIFR 3977 2.70374 -0.27314 0.00017 0.00460 LIMCH1 22998 1.21552 0.48834 0.00219 0.04146 LINC00996 285972 1.23250 1.23172 0.00035 0.00834 LINC01207 100505989 3.63335 -0.64034 0.00000 0.00002 LOC100288798 100288798 1.07192 -0.95770 0.00177 0.03452 LOC100507053 100507053 2.16556 -1.41283 0.00001 0.00045 LOC100507599 100507599 1.21793 -1.10264 0.00065 0.01434 LOC113230 113230 1.18190 -0.76286 0.00235 0.04388 LOC145474 145474 2.67731 -0.79558 0.00170 0.03319 LOC728208 728208 3.19171 -1.42646 0.00000 0.00000 LOC728763 728763 2.13235 -0.41999 0.00009 0.00235 LONRF2 164832 3.79980 -1.08032 0.00000 0.00000 LOX 4015 1.64059 -0.28114 0.00001 0.00019 LOXL4 84171 2.76685 0.21573 0.00000 0.00008 LPPR3 79948 3.29940 -0.74846 0.00000 0.00000 LRGUK 136332 1.84810 -0.56523 0.00000 0.00001 LRIG1 26018 0.81601 2.65112 0.00265 0.04847 LRIG3 121227 2.62236 -0.91393 0.00008 0.00231 LRP11 84918 1.00288 3.60793 0.00011 0.00298 LRP5 4041 1.54278 1.23081 0.00165 0.03251 LRP6 4040 1.50144 -0.25107 0.00111 0.02317 LRRC10B 390205 4.45323 0.50812 0.00000 0.00000 LRRC18 474354 2.74900 -0.98667 0.00000 0.00002 LRRC23 10233 1.68477 2.53750 0.00000 0.00000 LRRC43 254050 2.37743 -0.72869 0.00000 0.00003 LRRC46 90506 3.41638 1.56347 0.00000 0.00000 LRRC48 83450 2.90614 1.31625 0.00000 0.00000 LRRC49 54839 1.45823 0.37335 0.00002 0.00076 LRRC56 115399 1.51603 0.31624 0.00026 0.00652 LRRC71 149499 3.43616 -0.00125 0.00000 0.00000 LRRC73 221424 2.84579 -1.49591 0.00000 0.00015 LRRC74B 400891 2.94187 -0.10864 0.00001 0.00022 LRRIQ1 84125 4.45569 0.26038 0.00000 0.00000 LRRN1 57633 2.20073 -0.15692 0.00106 0.02223 LRTOMT 220074 0.86273 1.96604 0.00029 0.00717 LURAP1L 286343 2.59533 -0.59836 0.00044 0.01023 LYPD6B 130576 3.49960 -0.69024 0.00002 0.00050 MAATS1 89876 2.66527 1.01205 0.00000 0.00000

E28 MAGED1 9500 0.58473 4.08043 0.00137 0.02778 MAGIX 79917 0.69404 0.45805 0.00133 0.02714 MAL2 114569 2.82490 2.81336 0.00001 0.00021 MANF 7873 0.51011 5.64972 0.00231 0.04309 MAOA 4128 1.32647 2.36653 0.00111 0.02317 MAOB 4129 3.91817 -0.70807 0.00000 0.00000 MAP1A 4130 1.95526 2.08253 0.00000 0.00014 MAP1B 4131 3.67730 -0.31261 0.00000 0.00000 MAP3K19 80122 4.22828 0.18942 0.00000 0.00000 MAP6 4135 3.45308 0.38717 0.00000 0.00000 MAPK10 5602 2.94007 -0.18808 0.00000 0.00004 MAPK15 225689 3.09197 1.19155 0.00000 0.00000 MAPK8IP1 9479 2.13578 0.56343 0.00000 0.00000 MARCH10 162333 4.29242 -0.86093 0.00000 0.00000 MARK1 4139 2.48652 -0.77103 0.00031 0.00750 MARVELD2 153562 1.87503 -0.83180 0.00039 0.00918 MB 4151 3.47260 -0.87550 0.00000 0.00002 MCF2L 23263 2.66082 -0.11427 0.00000 0.00004 MDH1B 130752 3.55259 -0.18978 0.00000 0.00000 MECOM 2122 3.52605 0.78150 0.00000 0.00001 METRN 79006 0.92969 0.67223 0.00079 0.01712 MIA 8190 1.80549 -1.00280 0.00025 0.00630 MID1 4281 2.35500 -0.24186 0.00000 0.00000 MISP 126353 2.14894 2.19407 0.00093 0.01969 MMP10 4319 3.49878 2.78604 0.00001 0.00037 MNS1 55329 1.72660 0.68811 0.00001 0.00021 MOK 5891 1.15560 0.77600 0.00000 0.00016 MORN1 79906 1.02379 0.31756 0.00030 0.00734 MORN2 729967 0.81622 2.72241 0.00065 0.01450 MORN3 283385 1.79241 -0.75615 0.00001 0.00045 MORN5 254956 3.97950 -0.06599 0.00000 0.00000 MPDZ 8777 3.47762 -0.23758 0.00000 0.00000 MRAP2 112609 4.42900 -1.23826 0.00000 0.00000 MROH9 80133 4.33687 -1.47190 0.00000 0.00014 MS4A2 2206 3.06617 -0.45059 0.00000 0.00001 MS4A8 83661 5.25703 1.71397 0.00000 0.00000 MSMB 4477 2.65136 2.99402 0.00030 0.00734 MST1R 4486 1.89358 -0.48195 0.00025 0.00633 MT2A 4502 1.00645 5.83929 0.00021 0.00552 MTSS1L 92154 1.27787 1.80287 0.00001 0.00028 MUC13 56667 3.47934 1.08441 0.00001 0.00022 MUC15 143662 3.53383 0.34297 0.00000 0.00009 MUC16 94025 2.08219 4.38127 0.00032 0.00771 MUC2 4583 4.55163 1.69026 0.00001 0.00031 MUC5B 727897 1.63484 1.16337 0.00244 0.04517 MYCBPAP 84073 3.15755 -0.69175 0.00000 0.00000 MYH14 79784 2.10746 3.42922 0.00022 0.00556 MYLK 4638 2.76221 -1.06213 0.00000 0.00001 MYO1B 4430 2.24885 2.14322 0.00005 0.00147 MYO5C 55930 2.21435 1.49654 0.00000 0.00015 NAALADL2 254827 1.87075 -1.18483 0.00002 0.00064 NAT14 57106 1.45451 0.38151 0.00001 0.00043 NBEA 26960 1.45173 1.61100 0.00005 0.00146 NCALD 83988 1.87531 0.23075 0.00002 0.00075 NEBL 10529 2.30616 2.11632 0.00007 0.00194

E29 NEGR1 257194 1.73647 -1.00550 0.00015 0.00396 NEK10 152110 3.95592 -0.39251 0.00000 0.00000 NEK11 79858 0.98683 1.81645 0.00011 0.00309 NEK5 341676 3.90514 -1.20485 0.00000 0.00001 NFIB 4781 2.88024 -0.48999 0.00008 0.00214 NHLRC4 283948 2.34303 -0.37463 0.00000 0.00000 NME5 8382 4.80174 -0.05174 0.00000 0.00000 NME9 347736 1.33703 -0.36274 0.00036 0.00852 NOS2 4843 4.19110 2.54378 0.00000 0.00008 NPDC1 56654 1.49217 0.42324 0.00018 0.00460 NPHP1 4867 1.84417 0.93098 0.00000 0.00001 NPNT 255743 3.54607 -1.41567 0.00000 0.00017 NQO1 1728 0.85102 4.14926 0.00120 0.02487 NR2F2 7026 2.97920 -0.36696 0.00002 0.00053 NR2F6 2063 0.88930 1.88256 0.00044 0.01018 NRG4 145957 0.91166 -0.45898 0.00128 0.02623 NRXN3 9369 4.33939 -1.45057 0.00000 0.00001 NTRK1 4914 2.91627 -0.75410 0.00000 0.00009 NTRK2 4915 1.58241 -0.28924 0.00230 0.04299 NTS 4922 4.94395 0.88629 0.00000 0.00006 NUCB2 4925 0.51616 4.82465 0.00125 0.02572 NUDC 10726 0.37842 5.14157 0.00186 0.03598 NUDT16 131870 0.44937 5.10595 0.00242 0.04489 NWD1 284434 4.40393 1.26893 0.00000 0.00000 OBSL1 23363 1.57897 -0.37654 0.00050 0.01148 OCLM 10896 -0.83260 -0.53688 0.00197 0.03782 OLFM2 93145 1.63128 -0.29614 0.00010 0.00280 OLFML2A 169611 1.50245 -0.47892 0.00008 0.00232 OLFML3 56944 1.47139 -0.80882 0.00150 0.03004 OSBPL6 114880 3.46250 -0.07742 0.00000 0.00000 OSCP1 127700 1.25431 1.55984 0.00000 0.00012 OVOL2 58495 2.01869 -1.27468 0.00214 0.04055 OXTR 5021 3.75940 -0.10570 0.00000 0.00000 PACRG 135138 4.38754 -0.47598 0.00000 0.00000 PALMD 54873 3.98451 -0.93643 0.00000 0.00001 PARP15 165631 -0.80408 4.70068 0.00055 0.01259 PARVA 55742 1.79088 1.03887 0.00043 0.00996 PBX1 5087 2.72960 -0.32044 0.00002 0.00075 PCDH20 64881 2.40754 -1.54780 0.00002 0.00075 PCDH7 5099 2.90996 -0.62441 0.00005 0.00137 PCYT1B 9468 4.08988 -1.48044 0.00000 0.00000 PDE4A 5141 0.57356 5.68802 0.00069 0.01514 PDLIM4 8572 2.07893 1.04312 0.00000 0.00003 PFN2 5217 3.39152 1.53653 0.00000 0.00000 PHYHD1 254295 1.81583 -0.68865 0.00001 0.00039 PIFO 128344 4.47450 1.93612 0.00000 0.00000 PIGR 5284 4.40796 5.40916 0.00000 0.00000 PIH1D2 120379 1.93872 -0.30349 0.00000 0.00012 PIH1D3 139212 5.11786 -1.01760 0.00000 0.00000 PITPNM3 83394 1.42069 -0.13579 0.00032 0.00765 PLA1A 51365 -1.22498 2.27232 0.00220 0.04159 PLAC4 191585 1.84164 0.02246 0.00215 0.04077 PLCB4 5332 2.99905 0.53326 0.00000 0.00000 PLCE1 51196 2.94802 -0.06730 0.00000 0.00001 PLCH1 23007 4.12584 -0.38219 0.00000 0.00001

E30 PLEKHA5 54477 1.47875 2.13046 0.00001 0.00040 PLEKHG7 440107 2.50605 0.55103 0.00009 0.00238 PLEKHS1 79949 3.72463 1.80092 0.00000 0.00000 PLS1 5357 2.45456 2.12641 0.00001 0.00048 PLSCR4 57088 1.42562 -0.24175 0.00202 0.03859 PLXNB1 5364 1.68388 2.11949 0.00004 0.00107 PMEL 6490 1.15203 0.01103 0.00240 0.04459 PODXL 5420 1.65488 1.63778 0.00000 0.00015 POSTN 10631 7.10299 -0.36627 0.00000 0.00000 PPAP2C 8612 3.29265 0.89448 0.00000 0.00000 PPIL6 285755 2.84975 0.61883 0.00000 0.00000 PPP1R14A 94274 2.15578 -0.16637 0.00030 0.00734 PPP1R16A 84988 0.52389 3.07946 0.00057 0.01292 PPP1R32 220004 1.58631 0.52607 0.00000 0.00013 PPP1R36 145376 1.30213 -0.52794 0.00008 0.00214 PPP1R9A 55607 1.86074 -1.11869 0.00025 0.00630 PRB1 5542 8.18920 -0.84264 0.00000 0.00000 PRB3 5544 4.11931 -1.23298 0.00000 0.00001 PRICKLE2 166336 3.00884 -0.86531 0.00000 0.00005 PRKAA2 5563 3.32742 -0.57601 0.00000 0.00008 PRODH 5625 2.64131 0.01535 0.00004 0.00133 PROM1 8842 4.65762 2.06143 0.00000 0.00000 PRR15 222171 2.86216 1.36100 0.00000 0.00000 PRR15L 79170 2.09582 -0.82609 0.00035 0.00840 PRR29 92340 2.36678 1.35652 0.00000 0.00000 PRR4 11272 2.19959 0.83722 0.00000 0.00000 PRRT3 285368 1.00467 1.04872 0.00130 0.02652 PRSS12 8492 2.28162 0.74535 0.00000 0.00008 PRSS23 11098 2.31905 2.69389 0.00000 0.00008 PRSS33 260429 1.88563 0.64083 0.00001 0.00021 PTGDR2 11251 3.85345 -0.52100 0.00000 0.00000 PTK7 5754 2.47460 -0.25647 0.00001 0.00029 PTPRF 5792 2.67115 2.54391 0.00000 0.00001 PTPRN2 5799 1.70052 1.75165 0.00072 0.01569 PTPRT 11122 4.34988 0.00295 0.00000 0.00000 PTPRU 10076 1.68197 1.43127 0.00068 0.01505 PYCR1 5831 1.86497 -0.35529 0.00003 0.00097 PYROXD2 84795 0.98765 0.35597 0.00056 0.01270 PZP 5858 1.84792 0.29657 0.00000 0.00002 RAB36 9609 3.14824 0.76744 0.00000 0.00000 RAB3B 5865 3.95938 -1.29748 0.00000 0.00000 RAMP1 10267 1.62084 1.53200 0.00027 0.00664 RAP1GAP 5909 3.23997 0.30936 0.00000 0.00014 RASEF 158158 2.38207 -0.26795 0.00016 0.00412 RASSF6 166824 2.20563 -0.64517 0.00055 0.01264 RASSF9 9182 3.37782 -1.30392 0.00002 0.00076 RBM20 282996 3.30744 -1.51934 0.00000 0.00007 RBM24 221662 2.09154 -0.58814 0.00005 0.00155 RGS10 6001 0.57372 5.32555 0.00247 0.04562 RGS22 26166 4.87416 -0.32549 0.00000 0.00000 RHPN1 114822 0.84970 1.66657 0.00035 0.00844 RHPN2 85415 2.98048 0.48134 0.00000 0.00007 RIBC1 158787 2.79452 0.00077 0.00000 0.00000 RIBC2 26150 2.88560 -0.99734 0.00000 0.00001 ROPN1L 83853 2.91295 1.69582 0.00001 0.00035

E31 RP1 6101 4.69813 -1.38939 0.00000 0.00001 RPGRIP1L 23322 1.00389 0.74811 0.00131 0.02686 RPL21P28 100131205 0.64894 1.87845 0.00197 0.03790 RRAD 6236 2.01430 3.00194 0.00026 0.00649 RSPH1 89765 4.46388 2.00303 0.00000 0.00000 RSPH10B 222967 3.07839 -1.44737 0.00000 0.00009 RSPH14 27156 3.26569 -1.29097 0.00000 0.00008 RSPH4A 345895 3.71078 1.29074 0.00000 0.00000 RSPH9 221421 3.07364 0.35688 0.00000 0.00000 RTP4 64108 0.85729 2.41330 0.00089 0.01901 RUFY4 285180 1.47447 1.51868 0.00006 0.00170 RYR3 6263 1.68318 -0.35483 0.00001 0.00045 SAMD15 161394 1.66675 -0.94861 0.00008 0.00213 SAP30 8819 0.69675 2.33298 0.00062 0.01380 SAXO2 283726 4.14597 0.89981 0.00000 0.00000 SCAMP5 192683 0.98252 1.53015 0.00116 0.02395 SCARA3 51435 2.67693 -1.17482 0.00008 0.00231 SCD5 79966 1.44057 -0.98222 0.00034 0.00822 SCGB2A1 4246 4.07367 -1.44307 0.00003 0.00096 SCHIP1 29970 1.55742 -0.27607 0.00225 0.04232 SCN4B 6330 0.97828 -0.01590 0.00226 0.04251 SDK1 221935 3.12514 -0.18771 0.00000 0.00003 SDPR 8436 1.18803 -0.01368 0.00053 0.01210 SDSL 113675 0.63134 5.04559 0.00071 0.01560 SEC14L3 266629 3.72106 -1.44775 0.00001 0.00031 SELENBP1 8991 3.80597 1.93078 0.00000 0.00000 SEPT5 5413 2.11723 0.51764 0.00009 0.00238 SERPINB10 5273 5.61963 0.03390 0.00000 0.00000 SERPINB3 6317 2.92586 4.24964 0.00039 0.00915 SEZ6L2 26470 1.66474 -1.25027 0.00237 0.04405 SFTPB 6439 1.08428 -1.27833 0.00214 0.04057 SHANK2 22941 3.20315 -0.49263 0.00000 0.00004 SIGLEC8 27181 2.11815 0.10614 0.00000 0.00001 SIX1 6495 3.84333 0.04747 0.00000 0.00003 SIX2 10736 4.76434 -0.75356 0.00000 0.00000 SIX4 51804 3.70821 0.41282 0.00000 0.00001 SLC13A3 64849 3.97843 -0.79277 0.00000 0.00000 SLC16A9 220963 3.23720 0.79181 0.00001 0.00040 SLC22A16 85413 1.58295 0.70753 0.00026 0.00657 SLC23A1 9963 1.73716 -0.73067 0.00002 0.00068 SLC25A29 123096 0.49133 4.72365 0.00183 0.03543 SLC25A4 291 1.30562 0.55591 0.00024 0.00606 SLC26A4 5172 3.35327 1.43367 0.00000 0.00001 SLC26A4-AS1 286002 2.99527 -1.36397 0.00068 0.01510 SLC27A2 11001 3.30528 1.25671 0.00000 0.00000 SLC2A10 81031 3.82484 -0.02201 0.00000 0.00000 SLC2A12 154091 1.02371 0.16477 0.00022 0.00556 SLC34A2 10568 2.64094 1.83358 0.00000 0.00014 SLC44A4 80736 4.01521 3.38231 0.00000 0.00000 SLC4A4 8671 3.30258 -0.17567 0.00000 0.00001 SLC4A7 9497 -0.51240 4.88948 0.00230 0.04299 SLC51A 200931 1.25346 1.28903 0.00088 0.01886 SLC52A1 55065 1.79420 -1.53682 0.00004 0.00131 SLC5A8 160728 4.89367 1.23779 0.00000 0.00000 SLC6A14 11254 2.09762 4.70151 0.00257 0.04721

E32 SLC6A9 6536 1.72642 -0.43776 0.00168 0.03294 SLC7A2 6542 3.68160 0.89090 0.00000 0.00002 SLC9A3 6550 2.06241 0.92098 0.00061 0.01374 SLFN13 146857 0.76037 3.17656 0.00030 0.00724 SLITRK6 84189 3.25304 -0.49155 0.00017 0.00456 SLPI 6590 2.20361 6.44361 0.00002 0.00060 SMARCA1 6594 1.82206 -0.65262 0.00003 0.00091 SMIM22 440335 2.49294 0.40377 0.00001 0.00032 SMIM6 100130933 1.85409 -1.48022 0.00060 0.01342 SMPD3 55512 1.06096 1.96289 0.00029 0.00720 SNCAIP 9627 1.82538 -0.78626 0.00001 0.00045 SNHG16 100507246 0.83266 4.04178 0.00062 0.01385 SNTN 132203 4.82209 1.86591 0.00000 0.00000 SOCS2 8835 0.91590 3.05717 0.00100 0.02103 SOX2 6657 3.96445 0.84181 0.00000 0.00000 SOX21 11166 4.36329 0.37143 0.00000 0.00003 SOX21-AS1 100507533 3.86883 -0.65776 0.00000 0.00007 SPA17 53340 1.21345 1.62595 0.00001 0.00032 SPAG16 79582 0.86131 1.51051 0.00053 0.01228 SPAG17 200162 4.03560 1.07633 0.00000 0.00000 SPAG6 9576 4.68086 1.51480 0.00000 0.00000 SPAG8 26206 1.77368 0.74118 0.00000 0.00002 SPATA17 128153 3.03253 -0.68974 0.00000 0.00000 SPATA18 132671 2.95618 2.08545 0.00000 0.00000 SPATA33 124045 0.62822 1.00331 0.00188 0.03645 SPATA6L 55064 2.78762 -1.09622 0.00000 0.00003 SPDEF 25803 4.72237 1.39184 0.00000 0.00000 SPEF1 25876 3.55517 -0.18647 0.00000 0.00000 SPEF2 79925 1.67444 1.38100 0.00000 0.00009 SPINT2 10653 0.69915 6.71750 0.00004 0.00128 SPNS3 201305 1.84089 0.51056 0.00003 0.00091 SPON2 10417 1.46162 -0.65691 0.00036 0.00848 SPRN 503542 0.65065 1.06524 0.00147 0.02948 SRD5A2 6716 4.58000 -1.04494 0.00000 0.00000 SRGAP3-AS2 100507660 4.75698 0.34778 0.00000 0.00000 ST6GALNAC1 55808 4.16633 1.67663 0.00000 0.00000 STEAP2 261729 2.71018 -1.29073 0.00037 0.00863 STK33 65975 4.21259 0.03306 0.00000 0.00000 STMND1 401236 5.63329 -0.74941 0.00000 0.00000 STOML3 161003 5.06418 0.08058 0.00000 0.00000 STOX1 219736 3.63663 -0.52185 0.00000 0.00005 STRA6 64220 3.38215 -1.29388 0.00000 0.00002 STRN 6801 -0.52128 4.57302 0.00235 0.04388 SURF2 6835 0.61129 2.15567 0.00027 0.00678 SVEP1 79987 2.28396 -0.59377 0.00000 0.00002 SYBU 55638 3.82453 0.27447 0.00000 0.00000 SYNE3 161176 -0.67900 2.43433 0.00263 0.04817 SYTL2 54843 1.66978 3.04575 0.00001 0.00042 SYTL5 94122 2.86368 -0.42706 0.00006 0.00180 TACC2 10579 2.65601 1.50172 0.00002 0.00073 TCTE1 202500 5.13601 -1.42510 0.00000 0.00000 TCTEX1D1 200132 2.49248 0.00551 0.00002 0.00054 TCTEX1D2 255758 1.50471 0.32548 0.00000 0.00004 TEKT1 83659 4.77230 0.91867 0.00000 0.00000 TEKT2 27285 3.23435 0.58458 0.00000 0.00000

E33 TEKT4 150483 1.63507 -1.15528 0.00122 0.02523 TEX26 122046 4.77722 -1.09528 0.00000 0.00011 TEX9 374618 1.70055 -0.58359 0.00058 0.01304 TFF1 7031 3.95719 -1.29702 0.00001 0.00046 TFF3 7033 4.74380 2.92171 0.00000 0.00000 THRB 7068 1.65919 0.06407 0.00155 0.03093 TIMM10 26519 0.67742 4.04455 0.00025 0.00632 TMC4 147798 2.23349 2.53895 0.00001 0.00022 TMC5 79838 2.22060 3.28146 0.00023 0.00599 TMCC2 9911 1.61724 -0.59648 0.00012 0.00319 TMEM125 128218 4.25356 0.13611 0.00000 0.00000 TMEM190 147744 4.02531 0.89489 0.00000 0.00000 TMEM231 79583 1.42267 2.17973 0.00000 0.00000 TMEM232 642987 3.32676 -0.16413 0.00000 0.00000 TMEM30B 161291 2.67539 1.46050 0.00005 0.00142 TMEM67 91147 0.93749 1.77807 0.00194 0.03738 TMEM98 26022 3.66759 -0.51140 0.00000 0.00002 TMPRSS3 64699 1.93392 -0.34551 0.00005 0.00141 TMSB10 9168 0.51066 9.54379 0.00146 0.02936 TNFAIP8L1 126282 1.16763 2.99231 0.00000 0.00002 TNFRSF19 55504 5.05642 0.29321 0.00000 0.00000 TOM1L1 10040 1.37018 0.36406 0.00033 0.00788 TOMM34 10953 0.57546 4.26784 0.00022 0.00556 TOX3 27324 3.26735 -1.11377 0.00001 0.00023 TP73 7161 2.76145 -0.82408 0.00000 0.00008 TPPP3 51673 3.73695 3.00568 0.00000 0.00000 TPSAB1 7177 3.14133 1.92211 0.00001 0.00022 TPSB2 64499 2.84390 1.97391 0.00007 0.00188 TRIM7 81786 1.23040 -0.16263 0.00073 0.01596 TRIP13 9319 0.88137 1.03660 0.00163 0.03231 TRPV5 56302 -1.40223 -1.49287 0.00038 0.00897 TSGA10 80705 1.93923 0.31266 0.00000 0.00005 TSNAXIP1 55815 2.48252 0.05736 0.00000 0.00001 TSPAN1 10103 4.32787 4.84954 0.00000 0.00000 TSPAN11 441631 3.53579 -1.31227 0.00000 0.00008 TSPAN19 144448 5.49643 0.38357 0.00000 0.00000 TSPAN8 7103 6.25542 1.96958 0.00000 0.00000 TTC16 158248 2.98912 -0.58375 0.00000 0.00002 TTC25 83538 3.63968 0.25666 0.00000 0.00000 TTC26 79989 1.19450 0.85933 0.00005 0.00143 TTC29 83894 4.78703 -0.39129 0.00000 0.00000 TTC39A 22996 2.12260 0.47442 0.00004 0.00115 TTLL10 254173 3.19061 0.25048 0.00000 0.00000 TTLL10-AS1 100506376 3.27601 -1.58376 0.00000 0.00001 TTLL7 79739 1.66951 -1.29085 0.00018 0.00483 TTLL9 164395 1.75554 -1.12327 0.00029 0.00722 TUB 7275 2.82394 -0.58712 0.00000 0.00002 TUBA4B 80086 1.76573 1.00912 0.00092 0.01964 TUSC3 7991 4.58391 0.46311 0.00000 0.00000 UAP1 6675 0.60685 4.88663 0.00020 0.00528 UBXN10 127733 1.78178 1.92726 0.00000 0.00009 UGT2A1 10941 6.04422 0.88391 0.00000 0.00000 UNC119B 84747 0.64302 3.04391 0.00065 0.01446 UPK1B 7348 3.60148 2.54362 0.00001 0.00026 USP2 9099 0.81833 1.24933 0.00208 0.03977

E34 VANGL2 57216 2.18769 -0.43744 0.00022 0.00556 VMO1 284013 0.73648 4.83446 0.00142 0.02880 VSTM1 284415 2.53052 0.54687 0.00001 0.00023 VSTM2L 128434 4.11424 -0.13354 0.00000 0.00000 VTCN1 79679 2.32972 -0.06821 0.00023 0.00578 VWA3A 146177 3.51587 1.26141 0.00000 0.00000 VWA3B 200403 4.95927 0.85052 0.00000 0.00000 WDR34 89891 0.66478 2.63191 0.00140 0.02841 WDR38 401551 3.63172 0.72872 0.00000 0.00000 WDR54 84058 1.40740 1.54561 0.00000 0.00002 WDR63 126820 2.59241 0.20703 0.00000 0.00001 WDR66 144406 3.83103 1.38558 0.00000 0.00000 WDR78 79819 4.03665 0.94791 0.00000 0.00000 WDR86-AS1 100131176 2.75467 -0.41794 0.00000 0.00001 WDR93 56964 3.30309 -1.43670 0.00000 0.00001 WEE2-AS1 285962 0.91448 -0.56195 0.00245 0.04543 WFDC2 10406 2.69031 5.10316 0.00007 0.00212 WFDC6 140870 3.38733 -1.41508 0.00000 0.00011 WNK2 65268 2.04688 -0.23776 0.00027 0.00664 WNT5A 7474 1.80396 1.47436 0.00034 0.00816 WNT7B 7477 2.00736 -0.18398 0.00211 0.04027 XBP1 7494 0.52443 7.57454 0.00159 0.03155 ZBBX 79740 4.56626 0.72413 0.00000 0.00000 ZC2HC1C 79696 1.31176 -0.23354 0.00001 0.00042 ZDHHC1 29800 1.60568 0.25718 0.00000 0.00001 ZFAT 57623 1.17224 3.17564 0.00002 0.00076 ZMYND10 51364 3.44989 2.03092 0.00000 0.00000 ZNF204P 7754 1.62982 -0.13842 0.00026 0.00657 ZNF474 133923 2.86085 -0.65249 0.00000 0.00000 ZNF688 146542 0.47524 2.49220 0.00219 0.04146 ZNF750 79755 2.42489 0.79450 0.00026 0.00657

E35 Table E4. Differentially expressed genes in sputum from HDMS wheezers versus HDMS nonwheezers.

Gene Symbol Entrez ID logFC logCPM PValue FDR AADAC 13 5.05738 -1.54772 0.00000 0.00000 ABCA10 10349 1.52085 -1.43104 0.00016 0.00427 ABCA13 154664 3.35565 2.80247 0.00000 0.00001 ABCA5 23461 0.83934 3.46084 0.00024 0.00588 ABHD12B 145447 1.06117 0.06031 0.00104 0.02165 ABI2 10152 0.44320 3.47282 0.00167 0.03239 ACBD7 414149 2.08371 -1.36439 0.00001 0.00040 ADAMTS14 140766 1.38381 0.30814 0.00231 0.04265 ADAMTSL3 57188 4.45619 -1.44907 0.00000 0.00002 ADCY2 108 2.89459 -1.33464 0.00000 0.00008 ADCY6 112 1.10618 1.22601 0.00097 0.02045 ADGB 79747 3.52138 -0.26822 0.00000 0.00011 ADGRA3 166647 1.77096 -0.64074 0.00001 0.00024 ADGRF5 221395 3.09570 -1.41043 0.00000 0.00001 ADGRG1 9289 1.65644 2.82311 0.00067 0.01468 ADGRV1 84059 2.35156 -0.57164 0.00000 0.00012 ADH1C 126 3.99329 2.30533 0.00000 0.00005 ADH7 131 3.77048 1.58974 0.00000 0.00006 ADRA2A 150 4.91097 -0.17986 0.00000 0.00000 ADRB1 153 2.49593 -1.41522 0.00001 0.00048 AGBL2 79841 2.32108 0.72962 0.00000 0.00005 AGR2 10551 4.13829 4.67229 0.00000 0.00000 AGR3 155465 3.59630 1.17872 0.00000 0.00000 AK7 122481 3.89150 0.30564 0.00000 0.00002 AKAP14 158798 3.35263 -0.60615 0.00000 0.00009 AKAP6 9472 1.80195 -0.06240 0.00002 0.00080 AKT1S1 84335 0.76608 4.96030 0.00177 0.03402 ALOX15 246 4.60366 5.40730 0.00000 0.00000 ALS2CR12 130540 1.27292 -0.04034 0.00011 0.00305 AMOT 154796 2.46647 0.92148 0.00000 0.00000 ANG 283 0.76700 1.28844 0.00238 0.04384 ANK3 288 1.65319 1.45130 0.00000 0.00002 ANKK1 255239 1.48975 -1.22336 0.00006 0.00177 ANKRD45 339416 3.32106 -0.87217 0.00000 0.00017 ANKRD65 441869 2.18411 0.21215 0.00005 0.00158 ANKRD66 100287718 3.18896 -1.02946 0.00000 0.00001 ANKUB1 389161 2.95016 -0.30938 0.00000 0.00016 ANO1 55107 2.36467 0.24012 0.00046 0.01069 ANO7 50636 1.08264 -0.89370 0.00102 0.02142 AP1M2 10053 1.84364 0.98721 0.00083 0.01788 APCDD1 147495 2.16269 0.05373 0.00081 0.01749 APOBEC4 403314 3.80184 -0.36724 0.00000 0.00003 APOD 347 3.22966 -0.92482 0.00001 0.00041 ARFGEF3 57221 3.28825 1.74192 0.00000 0.00000 ARHGAP29 9411 2.06192 -1.22852 0.00020 0.00512 ARHGAP39 80728 1.39835 0.73945 0.00002 0.00064 ARHGAP42 143872 2.42955 -0.96978 0.00000 0.00019 ARHGEF37 389337 1.88350 0.72889 0.00179 0.03426 ARMC3 219681 3.90467 0.82775 0.00000 0.00000 ARMC4 55130 3.95595 0.01078 0.00000 0.00004 ASIC1 41 1.57018 -0.73942 0.00012 0.00323 ASTN2 23245 1.02811 -0.65583 0.00272 0.04883

E36 ATF5 22809 0.90696 5.96384 0.00028 0.00681 ATP13A5 344905 3.88182 -0.90289 0.00001 0.00050 ATP2C2 9914 2.22798 2.04503 0.00005 0.00158 ATP7B 540 1.82741 0.69746 0.00003 0.00098 AUTS2 26053 1.60904 2.05885 0.00000 0.00009 AXIN2 8313 1.70126 -0.69763 0.00001 0.00053 AZIN2 113451 1.10970 0.01634 0.00020 0.00512 B4GALNT3 283358 2.30747 0.61227 0.00001 0.00041 B4GALT4 8702 0.39304 4.25742 0.00244 0.04482 B9D1 27077 1.59884 0.11357 0.00000 0.00013 BCAM 4059 1.68440 -1.22299 0.00179 0.03426 BCAS1 8537 1.72174 2.50139 0.00195 0.03673 BCL2L14 79370 2.17653 1.06350 0.00055 0.01236 BCL2L15 440603 1.68077 0.12567 0.00024 0.00609 BCL7A 605 1.43281 1.40462 0.00180 0.03429 BEST4 266675 1.54813 0.04578 0.00089 0.01902 BEX5 340542 1.34183 -0.52442 0.00020 0.00508 BIK 638 1.50958 0.23708 0.00196 0.03674 BMP3 651 3.09460 -0.74909 0.00002 0.00081 BMPR1B 658 3.01280 -0.96659 0.00001 0.00025 BPIFB1 92747 4.72988 7.33747 0.00000 0.00000 BSPRY 54836 2.23276 0.03969 0.00003 0.00105 C10orf107 219621 3.54055 -0.29696 0.00000 0.00003 C10orf95 79946 0.95909 -0.45583 0.00138 0.02752 C11orf16 56673 3.03947 -0.05526 0.00000 0.00005 C11orf52 91894 2.90925 -0.90904 0.00000 0.00006 C11orf70 85016 3.78617 -0.05988 0.00000 0.00016 C11orf88 399949 3.23352 0.36227 0.00000 0.00001 C11orf97 643037 3.45034 -1.37620 0.00002 0.00053 C12orf45 121053 0.59163 2.51215 0.00053 0.01208 C14orf37 145407 1.39131 -1.23100 0.00013 0.00349 C15orf26 161502 2.83731 -0.74851 0.00000 0.00002 C16orf46 123775 1.07293 -0.40640 0.00010 0.00268 C16orf71 146562 2.63656 -0.44268 0.00000 0.00000 C16orf89 146556 3.03461 -1.00357 0.00000 0.00014 C1orf110 339512 3.61574 0.10907 0.00000 0.00006 C1orf141 400757 4.13667 -1.44916 0.00000 0.00004 C1orf158 93190 3.82238 -1.04087 0.00000 0.00002 C1orf168 199920 3.46028 -0.94784 0.00000 0.00000 C1orf189 388701 1.80862 -0.89289 0.00083 0.01786 C1orf194 127003 3.03448 0.51938 0.00000 0.00002 C1orf210 149466 2.21441 -1.42674 0.00112 0.02294 C1orf87 127795 3.80160 -0.06751 0.00000 0.00002 C20orf85 128602 3.26392 1.88592 0.00000 0.00000 C21orf58 54058 1.62058 0.64586 0.00001 0.00052 C22orf15 150248 2.79428 -0.71199 0.00000 0.00007 C2orf40 84417 3.17572 -0.25929 0.00002 0.00064 C2orf81 388963 0.94696 0.99849 0.00042 0.00983 C3orf67 200844 1.27884 -1.08505 0.00191 0.03597 C4orf47 441054 2.69494 -1.11165 0.00000 0.00007 C5orf49 134121 3.67070 0.24224 0.00000 0.00000 C6orf118 168090 3.98450 -0.28609 0.00000 0.00005 C6orf165 154313 3.72046 0.19129 0.00000 0.00000 C7orf57 136288 1.87911 0.20087 0.00000 0.00002 C8orf4 56892 2.78435 1.21940 0.00031 0.00746

E37 C9orf116 138162 2.41576 0.39155 0.00000 0.00002 C9orf117 286207 2.10698 1.43025 0.00000 0.00005 C9orf135 138255 3.45593 -0.21445 0.00000 0.00001 C9orf152 401546 3.15167 0.06120 0.00000 0.00003 C9orf171 389799 3.50751 -0.65288 0.00000 0.00001 C9orf24 84688 2.54889 1.14302 0.00000 0.00004 C9orf9 11092 1.25217 0.57568 0.00001 0.00025 CA12 771 1.56797 1.41190 0.00015 0.00395 CACHD1 57685 1.76552 -0.28203 0.00103 0.02153 CACNG6 59285 3.91854 -0.63144 0.00000 0.00015 CAP2 10486 4.22668 -0.81571 0.00000 0.00000 CAPN13 92291 3.11824 0.44552 0.00003 0.00091 CAPN8 388743 2.81356 -0.37717 0.00000 0.00002 CAPN9 10753 3.31315 -0.44140 0.00003 0.00095 CAPS 828 1.89237 4.11278 0.00000 0.00003 CAPS2 84698 1.97209 -0.37893 0.00000 0.00003 CAPSL 133690 3.81181 0.61992 0.00000 0.00000 CASC1 55259 3.26374 0.18127 0.00000 0.00001 CASC2 255082 1.92571 -0.90634 0.00001 0.00029 CATSPERD 257062 2.31140 -1.41907 0.00002 0.00055 CAV2 858 2.08894 -0.52069 0.00097 0.02048 CBS 875 -0.99851 3.82294 0.00174 0.03350 CCDC103 388389 1.10003 0.09798 0.00051 0.01171 CCDC108 255101 2.97610 0.74404 0.00001 0.00040 CCDC113 29070 2.65051 1.45200 0.00000 0.00000 CCDC114 93233 2.69072 1.16591 0.00000 0.00008 CCDC151 115948 1.70674 0.21657 0.00001 0.00032 CCDC17 149483 1.68172 3.16367 0.00000 0.00009 CCDC170 80129 1.05404 2.66412 0.00010 0.00267 CCDC173 129881 3.29721 -0.85957 0.00000 0.00001 CCDC176 80127 1.79284 1.43542 0.00000 0.00001 CCDC181 57821 2.30762 -0.69866 0.00000 0.00000 CCDC30 728621 1.00782 0.24102 0.00053 0.01205 CCDC33 80125 3.59054 -0.46857 0.00000 0.00019 CCDC37 348807 2.38990 0.56838 0.00004 0.00122 CCDC39 339829 1.31686 1.33479 0.00000 0.00009 CCDC40 55036 1.17423 1.64979 0.00034 0.00806 CCDC42B 387885 2.35181 0.14348 0.00000 0.00002 CCDC60 160777 3.78136 -0.68457 0.00000 0.00004 CCDC65 85478 1.98217 0.77110 0.00001 0.00025 CCDC74A 90557 2.54239 -0.47447 0.00000 0.00019 CCDC74B 91409 2.56971 -1.37370 0.00000 0.00012 CCDC78 124093 1.58743 2.11131 0.00006 0.00172 CCDC80 151887 2.46356 0.10875 0.00012 0.00337 CCDC81 60494 2.52957 0.22511 0.00000 0.00000 CCDC89 220388 3.12901 -1.11768 0.00001 0.00029 CCDC96 257236 0.75193 1.40221 0.00072 0.01567 CCL28 56477 1.23489 -1.37438 0.00186 0.03510 CCNA1 8900 1.27100 0.55346 0.00086 0.01849 CCNO 10309 3.20375 -0.51631 0.00000 0.00001 CD164L2 388611 3.21371 -0.38927 0.00000 0.00015 CD24 100133941 2.74068 4.83242 0.00000 0.00014 CDC20B 166979 4.32238 -0.15087 0.00000 0.00003 CDC42EP5 148170 2.23271 1.37094 0.00058 0.01293 CDH1 999 2.28477 3.09516 0.00002 0.00061

E38 CDH26 60437 3.35319 2.55003 0.00000 0.00000 CDH3 1001 2.29107 0.77602 0.00178 0.03408 CDHR3 222256 3.86974 2.47440 0.00000 0.00000 CDHR4 389118 3.22197 1.02589 0.00000 0.00008 CDKL2 8999 1.45672 -1.44165 0.00039 0.00928 CDON 50937 2.12442 -1.19346 0.00001 0.00027 CEBPE 1053 1.41215 0.66164 0.00001 0.00025 CEP112 201134 0.77387 0.23872 0.00131 0.02637 CEP126 57562 1.91486 0.87028 0.00000 0.00001 CERKL 375298 0.77350 1.12025 0.00056 0.01261 CETN2 1069 0.52314 4.64628 0.00119 0.02419 CFAP126 257177 1.32036 1.28318 0.00001 0.00024 CFAP221 200373 3.63943 0.16289 0.00000 0.00002 CFAP43 80217 3.66485 1.90812 0.00000 0.00000 CFAP44 55779 1.06729 2.42167 0.00025 0.00627 CFAP45 25790 2.16214 2.24416 0.00012 0.00322 CFAP46 54777 2.24085 -0.51184 0.00099 0.02087 CFAP52 146845 3.58276 0.53648 0.00000 0.00002 CFAP53 220136 2.68133 0.13038 0.00000 0.00000 CFAP57 149465 3.84725 -1.01566 0.00000 0.00005 CFAP61 26074 2.71000 -0.41652 0.00000 0.00000 CFAP69 79846 2.54110 0.06391 0.00000 0.00000 CFAP70 118491 1.81224 0.89080 0.00000 0.00016 CFAP74 85452 3.46291 -1.28926 0.00002 0.00067 CFAP99 402160 2.71978 -1.18414 0.00001 0.00039 CFH 3075 1.50392 1.29197 0.00071 0.01552 CFI 3426 1.75951 -0.30192 0.00039 0.00919 CFTR 1080 3.65623 -0.55887 0.00000 0.00001 CGN 57530 2.04221 2.14491 0.00029 0.00702 CH25H 9023 1.89411 1.60786 0.00001 0.00040 CHL1 10752 2.67126 0.37797 0.00007 0.00203 CHPF 79586 1.05414 2.54135 0.00003 0.00096 CHST6 4166 4.57586 1.49209 0.00000 0.00000 CHST9 83539 3.77125 0.86974 0.00000 0.00001 CLC 1178 2.41947 2.55598 0.00003 0.00099 CLCA1 1179 6.25856 3.43316 0.00000 0.00003 CLCA2 9635 2.72240 0.74797 0.00005 0.00149 CLDN10 9071 3.47539 -0.58234 0.00001 0.00048 CLDN3 1365 2.96737 0.96824 0.00000 0.00003 CLIC6 54102 3.58774 2.12700 0.00000 0.00000 CLU 1191 3.09366 3.15460 0.00000 0.00000 CLUAP1 23059 0.73525 2.59960 0.00217 0.04044 CMPK2 129607 0.81590 5.13260 0.00251 0.04570 CMTM4 146223 2.04535 1.86909 0.00000 0.00000 CMYA5 202333 3.31233 0.56709 0.00000 0.00000 CNGA4 1262 2.68572 -0.83757 0.00000 0.00002 COBL 23242 2.47877 0.11588 0.00002 0.00073 COL21A1 81578 2.93413 -0.97744 0.00012 0.00321 COL28A1 340267 2.89088 -1.16060 0.00003 0.00096 COL4A5 1287 3.31605 -0.96997 0.00002 0.00076 COLCA1 399948 4.41721 0.43082 0.00000 0.00000 COLCA2 120376 4.05370 -1.57003 0.00000 0.00014 CP 1356 3.01675 2.08888 0.00000 0.00002 CPA3 1359 2.34998 1.91325 0.00019 0.00496 CREB3L1 90993 3.69602 1.14103 0.00000 0.00001

E39 CREB3L4 148327 0.78423 1.46503 0.00161 0.03128 CRISPLD1 83690 2.75789 -1.44548 0.00000 0.00000 CRNDE 643911 1.71334 0.23097 0.00000 0.00001 CROCC 9696 0.63039 2.90534 0.00103 0.02148 CST1 1469 5.27419 3.01298 0.00000 0.00002 CST2 1470 3.16855 -0.18703 0.00053 0.01205 CST4 1472 3.81729 -0.72061 0.00015 0.00410 CTNS 1497 0.45725 5.02591 0.00121 0.02457 CTTN 2017 1.47131 2.74528 0.00089 0.01902 CTXN1 404217 2.75662 -0.45719 0.00000 0.00004 CX3CL1 6376 2.21920 -0.34489 0.00010 0.00278 CXCL17 284340 2.33177 3.70186 0.00023 0.00579 CXorf57 55086 0.76000 0.33186 0.00260 0.04709 CYB561 1534 0.61579 3.67402 0.00013 0.00346 CYP2A13 1553 2.60396 -1.41681 0.00138 0.02750 CYP2B7P 1556 2.13863 1.61846 0.00010 0.00274 CYP2C18 1562 2.42339 -1.09051 0.00091 0.01923 CYP2F1 1572 2.93131 0.88142 0.00001 0.00035 CYP2J2 1573 2.89058 -0.80530 0.00002 0.00056 CYP4B1 1580 3.74351 2.61711 0.00000 0.00004 CYP4X1 260293 2.49579 -0.96935 0.00042 0.00990 DACH1 1602 1.54002 -0.41033 0.00168 0.03257 DAW1 164781 3.63376 -0.14511 0.00000 0.00001 DBNDD1 79007 1.81798 -1.43644 0.00107 0.02197 DCBLD2 131566 0.64194 2.27494 0.00077 0.01670 DCDC2B 149069 0.84511 0.93567 0.00247 0.04525 DCDC5 100506627 2.76931 -1.36558 0.00000 0.00003 DDAH1 23576 2.94875 0.30983 0.00000 0.00004 DDR1 780 1.70424 3.62324 0.00002 0.00057 DEGS2 123099 2.64077 -0.63134 0.00000 0.00002 DENND6B 414918 0.83728 1.62971 0.00030 0.00730 DHX58 79132 0.67760 5.05764 0.00181 0.03454 DIRC3 729582 -2.04012 -1.05953 0.00056 0.01252 DLEC1 9940 1.27118 2.78038 0.00060 0.01329 DLG3 1741 1.83365 1.49058 0.00004 0.00132 DMTN 2039 1.84942 -0.06890 0.00000 0.00004 DNAAF1 123872 3.03810 2.29543 0.00000 0.00001 DNAAF3 352909 2.76542 0.38279 0.00000 0.00006 DNAH10 196385 2.86507 1.39591 0.00000 0.00001 DNAH11 8701 3.23179 0.95601 0.00000 0.00000 DNAH12 201625 3.34663 1.83912 0.00000 0.00002 DNAH2 146754 2.74747 1.24030 0.00000 0.00002 DNAH3 55567 2.81340 1.86750 0.00000 0.00010 DNAH5 1767 3.78561 2.22698 0.00000 0.00000 DNAH6 1768 2.68803 0.89946 0.00000 0.00010 DNAH7 56171 2.80993 0.80324 0.00000 0.00000 DNAH9 1770 3.60955 1.75783 0.00000 0.00002 DNAI1 27019 3.03942 0.96294 0.00001 0.00040 DNAI2 64446 2.82749 0.60499 0.00000 0.00012 DNAJB13 374407 1.31149 0.27397 0.00027 0.00656 DNAJC12 56521 1.46835 -1.30346 0.00043 0.01002 DNALI1 7802 2.15910 1.68768 0.00000 0.00000 DNASE1L3 1776 1.77104 2.56850 0.00017 0.00453 DNER 92737 3.40447 -0.95511 0.00000 0.00004 DPCD 25911 0.76104 1.66017 0.00050 0.01139

E40 DPY19L2P2 349152 2.27138 -1.15009 0.00005 0.00149 DRC1 92749 3.64566 1.05393 0.00000 0.00000 DSG2 1829 1.37262 1.49881 0.00043 0.00993 DTHD1 401124 3.68597 1.04574 0.00000 0.00000 DTX3 196403 1.51423 0.62928 0.00107 0.02197 DUOX1 53905 1.93789 2.69918 0.00035 0.00834 DYDC2 84332 3.92496 -0.19877 0.00000 0.00001 DYNLRB2 83657 3.11169 -0.38763 0.00000 0.00001 DZIP1 22873 2.65448 -1.20135 0.00003 0.00094 ECT2L 345930 2.68109 0.78362 0.00000 0.00000 EFCAB1 79645 3.14311 1.06329 0.00000 0.00000 EFCAB10 100130771 2.57995 -1.47589 0.00000 0.00006 EFCAB6 64800 1.97713 -0.22621 0.00000 0.00006 EFEMP1 2202 3.82642 -0.04456 0.00000 0.00002 EFHB 151651 3.24563 0.18714 0.00000 0.00000 EFHC1 114327 1.22344 3.32792 0.00001 0.00046 EFHC2 80258 2.74592 0.76469 0.00000 0.00006 EGFR 1956 2.12742 -0.54709 0.00178 0.03408 EML1 2009 2.29492 -0.25768 0.00002 0.00064 ENAH 55740 3.00848 1.11261 0.00000 0.00000 ENDOG 2021 0.67124 1.07236 0.00124 0.02518 ENKUR 219670 4.22371 0.72256 0.00000 0.00000 ENO4 387712 0.97678 0.04940 0.00029 0.00702 ENTPD3 956 2.38534 -0.84432 0.00005 0.00139 EPB41L4B 54566 3.48901 0.92841 0.00000 0.00000 EPCAM 4072 3.32434 1.13868 0.00000 0.00000 EPHX2 2053 2.28279 -0.76068 0.00000 0.00004 EPPIN 57119 2.76541 -1.43253 0.00019 0.00484 EPS8 2059 0.75557 3.07944 0.00232 0.04277 ERBB2 2064 1.51142 2.33867 0.00004 0.00120 ERBB4 2066 5.02762 -0.71719 0.00000 0.00003 ERICH3 127254 4.24031 1.72467 0.00000 0.00000 ERICH5 203111 2.68447 -0.88368 0.00000 0.00005 ERN2 10595 3.36777 1.34204 0.00000 0.00004 ESP33 100188917 2.11037 -0.22029 0.00175 0.03370 ESPN 83715 1.05122 -0.21184 0.00165 0.03204 ESRRG 2104 2.59049 -1.36134 0.00008 0.00228 EYA1 2138 3.44484 -0.62120 0.00000 0.00003 EYA4 2070 3.54635 -0.26549 0.00000 0.00002 FA2H 79152 2.37104 0.20636 0.00045 0.01049 FAAH2 158584 1.77039 -0.59898 0.00031 0.00753 FABP6 2172 1.96445 -0.60128 0.00132 0.02648 FAM149A 25854 1.63288 0.00312 0.00004 0.00111 FAM161A 84140 1.13087 -0.28252 0.00017 0.00449 FAM166B 730112 2.67973 0.20046 0.00000 0.00012 FAM169A 26049 0.97932 0.17421 0.00067 0.01467 FAM171A1 221061 2.47903 -0.96832 0.00000 0.00003 FAM174B 400451 1.55947 0.39782 0.00006 0.00183 FAM179A 165186 1.99194 1.58074 0.00000 0.00013 FAM183A 440585 2.41610 0.41080 0.00000 0.00020 FAM184A 79632 1.86966 -0.66753 0.00000 0.00008 FAM188B 84182 1.16809 0.16186 0.00010 0.00280 FAM216B 144809 4.03250 2.01312 0.00000 0.00000 FAM227A 646851 2.78503 0.03738 0.00000 0.00000 FAM229B 619208 1.43303 0.69056 0.00001 0.00022

E41 FAM47E 100129583 1.50490 0.25058 0.00004 0.00111 FAM81A 145773 1.62536 -0.90996 0.00031 0.00750 FAM81B 153643 3.14802 0.32300 0.00000 0.00001 FAM83E 54854 2.57940 0.46277 0.00003 0.00097 FAM83H-AS1 100128338 2.60394 -0.74514 0.00000 0.00002 FAM92B 339145 3.75794 0.92434 0.00000 0.00000 FAM95C 100289137 2.60840 -1.36407 0.00000 0.00010 FANK1 92565 2.36683 0.91758 0.00000 0.00000 FAT1 2195 1.74533 1.41121 0.00267 0.04811 FBXO15 201456 1.82359 -0.16702 0.00005 0.00147 FBXO36 130888 1.08785 0.41565 0.00054 0.01226 FBXW9 84261 0.75632 0.97754 0.00048 0.01105 FCGBP 8857 3.02528 4.83826 0.00000 0.00004 FER1L6 654463 2.11723 1.75093 0.00029 0.00719 FETUB 26998 6.00310 -1.41739 0.00000 0.00000 FGF14 2259 4.01862 -1.39321 0.00000 0.00004 FGFR2 2263 1.99982 0.12220 0.00030 0.00743 FILIP1 27145 3.18402 -1.39865 0.00000 0.00006 FMOD 2331 1.61141 -1.00578 0.00013 0.00361 FOXA1 3169 2.43106 2.18689 0.00006 0.00179 FOXA3 3171 5.03377 -1.06352 0.00000 0.00001 FOXJ1 2302 3.76635 2.11313 0.00000 0.00000 FRMPD2 143162 3.76070 -0.93494 0.00001 0.00022 FSTL1 11167 1.67024 1.76966 0.00169 0.03261 FXYD3 5349 3.07037 2.81887 0.00000 0.00006 FZD3 7976 2.07962 -1.27094 0.00000 0.00011 FZD4 8322 0.94262 0.98649 0.00167 0.03241 FZD6 8323 2.49769 0.88489 0.00000 0.00000 GALNT18 374378 3.34600 -1.19460 0.00002 0.00056 GAS2L2 246176 2.80410 0.25830 0.00005 0.00159 GAS8 2622 0.60935 1.97970 0.00134 0.02678 GCNT4 51301 2.11332 -1.18305 0.00000 0.00001 GJB5 2709 2.46572 -1.21535 0.00134 0.02682 GLB1L2 89944 2.26537 -0.32757 0.00000 0.00001 GMNC 647309 2.07796 -1.37355 0.00010 0.00281 GNA14 9630 1.64374 0.22071 0.00034 0.00823 GNLY 10578 2.14960 3.72113 0.00061 0.01360 GPRC5C 55890 1.40587 0.50767 0.00133 0.02667 GPX2 2877 2.23275 0.62426 0.00054 0.01223 GPX8 493869 2.12004 -0.86504 0.00000 0.00004 GRAMD2 196996 2.50287 -1.50703 0.00022 0.00554 GRHL2 79977 3.29128 0.15379 0.00000 0.00005 GSTA1 2938 3.04589 1.44222 0.00000 0.00005 GSTA2 2939 3.12518 0.36670 0.00000 0.00016 GUCY1A3 2982 1.45430 -0.77167 0.00002 0.00053 HESX1 8820 1.33342 0.13182 0.00091 0.01925 HHLA2 11148 2.71179 -0.88983 0.00000 0.00019 HID1 283987 3.01231 0.35261 0.00000 0.00003 HMGB3 3149 0.72355 2.60965 0.00002 0.00057 HMGCS2 3158 2.88847 -1.00959 0.00037 0.00881 HOOK1 51361 2.02518 1.29045 0.00002 0.00064 HRASLS2 54979 2.91493 -0.98353 0.00000 0.00009 HRASLS5 117245 1.35476 -0.38921 0.00116 0.02374 HRH4 59340 1.69269 0.25158 0.00009 0.00242 HS6ST2 90161 2.84671 -1.45802 0.00001 0.00049

E42 HSD17B13 345275 3.51473 0.61765 0.00000 0.00000 HSPA4L 22824 1.87519 -0.58576 0.00001 0.00036 HTATSF1P2 401233 -0.75619 3.90388 0.00140 0.02787 HYDIN 54768 3.10850 1.45214 0.00000 0.00002 IFT22 64792 0.82598 2.11487 0.00058 0.01299 IFT80 57560 0.58682 2.99286 0.00107 0.02205 IFT81 28981 1.18056 1.29424 0.00001 0.00022 IGFBP5 3488 4.05712 0.77678 0.00000 0.00000 IGFBP7 3490 1.58018 2.03145 0.00000 0.00003 IGSF3 3321 1.10780 -0.16134 0.00139 0.02756 IL20RA 53832 3.78093 -0.98573 0.00000 0.00004 IL33 90865 2.74408 -0.59470 0.00022 0.00554 IL5RA 3568 2.51710 -1.18566 0.00013 0.00355 ILDR1 286676 1.34863 -0.20548 0.00010 0.00274 INHBB 3625 1.63190 -0.50471 0.00099 0.02084 IQCA1 79781 1.22361 0.17311 0.00152 0.02992 IQCD 115811 2.10865 -0.05088 0.00009 0.00242 IQCG 84223 0.69076 3.39218 0.00103 0.02147 IQCH 64799 2.52697 -0.96483 0.00000 0.00000 IQUB 154865 3.25369 -0.85679 0.00000 0.00005 IRX3 79191 2.86407 -0.36518 0.00001 0.00032 IRX5 10265 2.70510 -1.35533 0.00002 0.00072 ITLN1 55600 1.56805 2.26280 0.00075 0.01640 KATNAL2 83473 0.86171 0.13093 0.00160 0.03128 KCNH3 23416 1.59685 0.36262 0.00265 0.04787 KCNJ16 3773 5.43417 -0.21957 0.00000 0.00000 KCNRG 283518 1.69338 -0.54207 0.00000 0.00017 KCTD1 284252 1.18218 0.46788 0.00008 0.00230 KCTD14 65987 1.87082 -1.30541 0.00012 0.00330 KIAA0895 23366 2.52686 -0.43425 0.00000 0.00001 KIAA1211 57482 2.09852 -0.58438 0.00002 0.00059 KIAA1211L 343990 0.99930 1.90461 0.00014 0.00368 KIAA1217 56243 1.80250 1.61333 0.00105 0.02175 KIAA1456 57604 1.25171 -0.19746 0.00018 0.00459 KIAA1549 57670 3.28330 -0.61230 0.00000 0.00001 KIAA1671 85379 1.80878 1.68709 0.00001 0.00040 KIF19 124602 2.84182 0.05216 0.00000 0.00014 KIF21A 55605 2.28147 1.76665 0.00000 0.00000 KLHDC7A 127707 4.50771 -0.61259 0.00000 0.00000 KLHDC9 126823 1.46254 -0.67573 0.00002 0.00063 KLHL13 90293 2.80184 -1.42398 0.00001 0.00024 KNDC1 85442 2.19950 0.03493 0.00007 0.00194 KRT8 3856 2.00501 3.53816 0.00030 0.00726 KRTCAP3 200634 0.95398 0.09210 0.00023 0.00587 LAMA3 3909 1.19236 0.52725 0.00136 0.02711 LARP6 55323 1.65762 -0.76695 0.00002 0.00056 LAYN 143903 1.38489 -0.25936 0.00044 0.01019 LCA5 167691 1.60210 0.49667 0.00006 0.00180 LCA5L 150082 1.49046 -0.66825 0.00011 0.00306 LDLRAD1 388633 3.88615 -0.35331 0.00000 0.00002 LGALS12 85329 1.85966 1.15563 0.00008 0.00225 LIFR 3977 2.72238 -0.27314 0.00007 0.00195 LIMCH1 22998 1.36669 0.48834 0.00035 0.00834 LINC00865 643529 1.13069 -0.88741 0.00094 0.01998 LINC01207 100505989 3.31779 -0.64034 0.00000 0.00003

E43 LOC100288798 100288798 1.04164 -0.95770 0.00169 0.03259 LOC100499489 100499489 0.58122 1.25313 0.00260 0.04709 LOC100506844 100506844 0.72728 0.87431 0.00098 0.02061 LOC100507053 100507053 1.81391 -1.41283 0.00013 0.00342 LOC100507291 100507291 0.76051 -0.78542 0.00247 0.04525 LOC100507599 100507599 1.07310 -1.10264 0.00187 0.03531 LOC728208 728208 2.05053 -1.42646 0.00016 0.00414 LONRF2 164832 3.32960 -1.08032 0.00000 0.00000 LOX 4015 1.28676 -0.28114 0.00012 0.00326 LOXL4 84171 2.77210 0.21573 0.00000 0.00002 LPPR3 79948 2.60233 -0.74846 0.00000 0.00016 LRGUK 136332 1.73111 -0.56523 0.00000 0.00003 LRIG1 26018 1.18116 2.65112 0.00001 0.00025 LRIG3 121227 2.60565 -0.91393 0.00005 0.00149 LRP11 84918 1.08901 3.60793 0.00001 0.00038 LRP2BP 55805 1.12866 -0.37295 0.00083 0.01784 LRP6 4040 1.50305 -0.25107 0.00063 0.01386 LRRC10B 390205 3.75736 0.50812 0.00000 0.00001 LRRC18 474354 2.77637 -0.98667 0.00000 0.00002 LRRC23 10233 1.37486 2.53750 0.00000 0.00005 LRRC43 254050 2.49397 -0.72869 0.00000 0.00001 LRRC46 90506 2.81010 1.56347 0.00000 0.00000 LRRC48 83450 2.51822 1.31625 0.00000 0.00000 LRRC49 54839 1.38727 0.37335 0.00004 0.00110 LRRC56 115399 1.35853 0.31624 0.00067 0.01468 LRRC71 149499 2.53618 -0.00125 0.00000 0.00005 LRRC73 221424 2.38531 -1.49591 0.00004 0.00116 LRRC74B 400891 2.06098 -0.10864 0.00084 0.01800 LRRIQ1 84125 3.90728 0.26038 0.00000 0.00001 LRTOMT 220074 0.80923 1.96604 0.00041 0.00959 LTK 4058 1.22021 0.49313 0.00230 0.04246 LURAP1L 286343 2.07198 -0.59836 0.00239 0.04384 LYPD6B 130576 3.14896 -0.69024 0.00003 0.00098 MAATS1 89876 2.75046 1.01205 0.00000 0.00000 MAGED1 9500 0.78597 4.08043 0.00001 0.00031 MAGEF1 64110 0.88741 1.21540 0.00104 0.02154 MAL2 114569 2.68151 2.81336 0.00001 0.00021 MAOA 4128 1.46983 2.36653 0.00015 0.00407 MAOB 4129 3.26117 -0.70807 0.00000 0.00000 MAP1A 4130 2.14836 2.08253 0.00000 0.00001 MAP1B 4131 3.04199 -0.31261 0.00000 0.00000 MAP3K19 80122 3.60929 0.18942 0.00000 0.00001 MAP6 4135 2.86815 0.38717 0.00000 0.00002 MAP9 79884 1.44228 1.18440 0.00002 0.00078 MAPK10 5602 2.73109 -0.18808 0.00000 0.00009 MAPK15 225689 2.25212 1.19155 0.00000 0.00016 MAPK8IP1 9479 1.35493 0.56343 0.00008 0.00228 MARC2 54996 1.46346 -0.97518 0.00175 0.03370 MARCH10 162333 3.52418 -0.86093 0.00000 0.00001 MARK1 4139 2.51430 -0.77103 0.00013 0.00359 MARVELD2 153562 2.01792 -0.83180 0.00007 0.00203 MATN2 4147 1.52591 -1.41994 0.00083 0.01788 MB 4151 3.06912 -0.87550 0.00000 0.00010 MCF2L 23263 2.84700 -0.11427 0.00000 0.00001 MDH1B 130752 3.14658 -0.18978 0.00000 0.00000

E44 MECOM 2122 3.75666 0.78150 0.00000 0.00000 MET 4233 1.32928 2.66933 0.00249 0.04537 MID1 4281 1.91655 -0.24186 0.00000 0.00012 MNS1 55329 1.79006 0.68811 0.00000 0.00006 MOK 5891 1.02374 0.77600 0.00002 0.00072 MORN2 729967 0.85697 2.72241 0.00020 0.00518 MORN5 254956 3.16569 -0.06599 0.00000 0.00001 MPDZ 8777 2.92281 -0.23758 0.00000 0.00005 MRAP2 112609 3.72711 -1.23826 0.00000 0.00004 MROH9 80133 3.36088 -1.47190 0.00008 0.00225 MS4A2 2206 2.33005 -0.45059 0.00001 0.00051 MS4A8 83661 4.18318 1.71397 0.00000 0.00000 MSMB 4477 2.66808 2.99402 0.00016 0.00426 MST1R 4486 1.72423 -0.48195 0.00036 0.00862 MT2A 4502 0.97641 5.83929 0.00019 0.00488 MTSS1L 92154 1.08172 1.80287 0.00007 0.00199 MUC13 56667 3.55049 1.08441 0.00000 0.00006 MUC15 143662 3.45604 0.34297 0.00000 0.00007 MUC16 94025 1.73775 4.38127 0.00183 0.03480 MUC2 4583 3.47106 1.69026 0.00025 0.00627 MUC5B 727897 2.05977 1.16337 0.00008 0.00228 MYCBPAP 84073 2.53513 -0.69175 0.00000 0.00011 MYH14 79784 1.67500 3.42922 0.00204 0.03831 MYLK 4638 2.48423 -1.06213 0.00000 0.00005 MYO1B 4430 2.46571 2.14322 0.00000 0.00016 MYO1D 4642 1.06691 3.16363 0.00192 0.03612 MYO5C 55930 2.02977 1.49654 0.00001 0.00035 MYO9B 4650 -0.36388 8.89301 0.00186 0.03510 NAALADL2 254827 1.39533 -1.18483 0.00082 0.01780 NAIP 4671 -0.81657 3.90294 0.00065 0.01426 NAT14 57106 1.15780 0.38151 0.00028 0.00691 NAV2 89797 1.35683 2.17972 0.00005 0.00149 NBEA 26960 1.76688 1.61100 0.00000 0.00002 NBL1 4681 1.35678 1.69343 0.00149 0.02929 NCALD 83988 2.14066 0.23075 0.00000 0.00004 NCOA7 135112 0.51760 5.67423 0.00266 0.04801 NEBL 10529 2.24476 2.11632 0.00005 0.00149 NEGR1 257194 1.34501 -1.00550 0.00160 0.03128 NEK10 152110 3.28080 -0.39251 0.00000 0.00002 NEK11 79858 0.88614 1.81645 0.00033 0.00804 NEK5 341676 3.31211 -1.20485 0.00000 0.00010 NELL2 4753 1.69539 1.20958 0.00017 0.00449 NFASC 23114 2.21217 -1.01964 0.00051 0.01166 NFIB 4781 3.11522 -0.48999 0.00001 0.00024 NHLRC4 283948 1.92747 -0.37463 0.00000 0.00002 NME2 4831 0.69625 0.52759 0.00154 0.03022 NME5 8382 3.87163 -0.05174 0.00000 0.00009 NME9 347736 1.18338 -0.36274 0.00106 0.02192 NOS2 4843 3.71478 2.54378 0.00001 0.00045 NPDC1 56654 1.82602 0.42324 0.00000 0.00005 NPHP1 4867 1.61181 0.93098 0.00000 0.00006 NPNT 255743 3.55720 -1.41567 0.00000 0.00008 NQO1 1728 0.92208 4.14926 0.00021 0.00526 NR2F2 7026 3.23413 -0.36696 0.00000 0.00007 NRSN2 80023 1.11584 -0.03886 0.00004 0.00112

E45 NRXN3 9369 4.33528 -1.45057 0.00000 0.00001 NTN1 9423 1.47935 1.06642 0.00090 0.01918 NTN4 59277 1.68576 1.13870 0.00225 0.04176 NTRK2 4915 2.37887 -0.28924 0.00000 0.00007 NTS 4922 4.13038 0.88629 0.00001 0.00038 NUCB2 4925 0.61764 4.82465 0.00006 0.00166 NUP62CL 54830 1.29382 -1.28457 0.00096 0.02037 NWD1 284434 3.82151 1.26893 0.00000 0.00004 OBSL1 23363 2.01747 -0.37654 0.00000 0.00013 OCIAD2 132299 0.91888 1.78586 0.00024 0.00600 ODF2L 57489 0.61394 3.39572 0.00039 0.00919 OLFM2 93145 1.29528 -0.29614 0.00104 0.02165 OLFML3 56944 1.39807 -0.80882 0.00166 0.03218 OSBPL6 114880 3.44328 -0.07742 0.00000 0.00000 OSCP1 127700 1.17508 1.55984 0.00000 0.00020 OVOL2 58495 2.17731 -1.27468 0.00063 0.01392 OXTR 5021 3.31793 -0.10570 0.00000 0.00000 PACRG 135138 3.27834 -0.47598 0.00000 0.00004 PALMD 54873 3.46427 -0.93643 0.00000 0.00009 PARVA 55742 2.64646 1.03887 0.00000 0.00001 PBX1 5087 2.82776 -0.32044 0.00000 0.00020 PCDH20 64881 2.43037 -1.54780 0.00001 0.00037 PCDH7 5099 3.36489 -0.62441 0.00000 0.00008 PCLO 27445 1.92560 -1.06219 0.00023 0.00576 PCYT1B 9468 3.11732 -1.48044 0.00001 0.00036 PDCL3 79031 0.44656 3.36595 0.00248 0.04534 PDE8B 8622 0.81152 1.49263 0.00254 0.04613 PDLIM2 64236 -0.47056 4.98647 0.00248 0.04532 PDLIM4 8572 1.41962 1.04312 0.00034 0.00821 PERP 64065 1.80003 4.15040 0.00120 0.02426 PFN2 5217 3.24266 1.53653 0.00000 0.00000 PHGDH 26227 0.87972 1.73107 0.00226 0.04202 PHLDB2 90102 1.39055 0.02344 0.00153 0.03010 PHYHD1 254295 2.05967 -0.68865 0.00000 0.00002 PIFO 128344 3.60640 1.93612 0.00000 0.00000 PIGR 5284 4.00504 5.40916 0.00000 0.00000 PIH1D2 120379 1.92320 -0.30349 0.00000 0.00010 PIH1D3 139212 4.06486 -1.01760 0.00000 0.00006 PIK3R3 8503 0.95911 2.15291 0.00006 0.00184 PITPNM3 83394 1.30936 -0.13579 0.00046 0.01063 PLCB4 5332 3.12525 0.53326 0.00000 0.00000 PLCE1 51196 2.83953 -0.06730 0.00000 0.00001 PLCH1 23007 4.02477 -0.38219 0.00000 0.00001 PLEKHA5 54477 1.29266 2.13046 0.00005 0.00144 PLEKHG5 57449 1.60512 -0.95653 0.00160 0.03128 PLEKHG7 440107 2.59145 0.55103 0.00003 0.00083 PLEKHH1 57475 1.04918 0.51771 0.00098 0.02068 PLEKHS1 79949 3.84042 1.80092 0.00000 0.00000 PLS1 5357 2.45059 2.12641 0.00001 0.00024 PLSCR4 57088 2.12441 -0.24175 0.00000 0.00009 PLXNB1 5364 1.54684 2.11949 0.00008 0.00220 PMEL 6490 1.37551 0.01103 0.00016 0.00427 PNPT1 87178 0.57514 4.49556 0.00146 0.02888 PODXL 5420 1.57414 1.63778 0.00000 0.00016 POSTN 10631 4.73923 -0.36627 0.00005 0.00149

E46 PPAP2C 8612 2.82301 0.89448 0.00000 0.00003 PPIL6 285755 2.24756 0.61883 0.00000 0.00000 PPP1R16A 84988 0.45405 3.07946 0.00183 0.03478 PPP1R32 220004 1.39829 0.52607 0.00002 0.00062 PPP1R36 145376 1.28601 -0.52794 0.00005 0.00146 PPP1R9A 55607 2.37027 -1.11869 0.00000 0.00009 PPP4R4 57718 1.88874 -1.44892 0.00021 0.00524 PRB1 5542 3.54815 -0.84264 0.00185 0.03504 PRB3 5544 2.50494 -1.23298 0.00027 0.00672 PRICKLE2 166336 2.95830 -0.86531 0.00000 0.00004 PRKAA2 5563 3.10617 -0.57601 0.00000 0.00009 PRODH 5625 3.02943 0.01535 0.00000 0.00004 PROM1 8842 4.01429 2.06143 0.00000 0.00000 PRPH 5630 2.12037 -1.32161 0.00085 0.01820 PRR15 222171 2.20038 1.36100 0.00000 0.00000 PRR15L 79170 2.40814 -0.82609 0.00002 0.00062 PRR29 92340 1.77453 1.35652 0.00000 0.00002 PRR4 11272 1.92490 0.83722 0.00000 0.00003 PRSS12 8492 2.32770 0.74535 0.00000 0.00003 PRSS23 11098 2.46011 2.69389 0.00000 0.00001 PRSS33 260429 1.27632 0.64083 0.00118 0.02403 PTGDR2 11251 2.68887 -0.52100 0.00000 0.00002 PTGFR 5737 3.08770 -1.35896 0.00010 0.00280 PTK7 5754 2.47356 -0.25647 0.00000 0.00012 PTPRF 5792 2.79375 2.54391 0.00000 0.00000 PTPRT 11122 3.88299 0.00295 0.00000 0.00001 PTPRU 10076 1.86944 1.43127 0.00009 0.00243 PTPRZ1 5803 3.00931 -0.22760 0.00014 0.00370 PXDC1 221749 0.47823 5.07496 0.00247 0.04522 PYCR1 5831 2.03274 -0.35529 0.00000 0.00011 PZP 5858 1.60840 0.29657 0.00000 0.00014 RAB36 9609 2.74154 0.76744 0.00000 0.00001 RAB3B 5865 3.25031 -1.29748 0.00000 0.00007 RAB6B 51560 0.86463 -0.57771 0.00268 0.04820 RAP1GAP 5909 2.54240 0.30936 0.00010 0.00285 RASEF 158158 2.09348 -0.26795 0.00050 0.01150 RASIP1 54922 1.74875 -1.11534 0.00179 0.03424 RASSF6 166824 2.71192 -0.64517 0.00001 0.00048 RASSF9 9182 3.48893 -1.30392 0.00000 0.00014 RBM20 282996 2.94735 -1.51934 0.00001 0.00033 RBM24 221662 2.06152 -0.58814 0.00004 0.00122 RGS22 26166 4.20555 -0.32549 0.00000 0.00002 RHOC 389 0.53466 5.12006 0.00087 0.01862 RHPN1 114822 0.81126 1.66657 0.00036 0.00852 RHPN2 85415 2.46675 0.48134 0.00002 0.00076 RIBC1 158787 2.21311 0.00077 0.00000 0.00001 RIBC2 26150 2.51741 -0.99734 0.00000 0.00008 RIMKLA 284716 1.18884 -1.27542 0.00118 0.02400 ROBO1 6091 1.12486 1.13462 0.00039 0.00928 ROPN1L 83853 2.37579 1.69582 0.00017 0.00445 RP1 6101 3.94847 -1.38939 0.00000 0.00009 RPGRIP1L 23322 1.17981 0.74811 0.00011 0.00299 RRAD 6236 1.78119 3.00194 0.00071 0.01546 RSPH1 89765 3.40491 2.00303 0.00000 0.00000 RSPH10B 222967 2.58224 -1.44737 0.00003 0.00109

E47 RSPH14 27156 3.07309 -1.29097 0.00000 0.00015 RSPH4A 345895 3.24722 1.29074 0.00000 0.00000 RSPH9 221421 2.32924 0.35688 0.00000 0.00002 RTP4 64108 0.89333 2.41330 0.00035 0.00837 RYR3 6263 1.84395 -0.35483 0.00000 0.00006 SAMD15 161394 1.37595 -0.94861 0.00067 0.01476 SAXO2 283726 3.97619 0.89981 0.00000 0.00001 SCARA3 51435 2.87519 -1.17482 0.00001 0.00043 SCD5 79966 1.58723 -0.98222 0.00004 0.00117 SCGB1A1 7356 2.15854 4.72794 0.00002 0.00064 SCGB2A1 4246 3.81081 -1.44307 0.00003 0.00108 SDK1 221935 2.84595 -0.18771 0.00000 0.00009 SDPR 8436 1.32277 -0.01368 0.00005 0.00162 SDR42E1 93517 1.49209 -1.22024 0.00137 0.02743 SDSL 113675 0.61806 5.04559 0.00049 0.01119 SEC14L3 266629 3.95940 -1.44775 0.00000 0.00006 SELENBP1 8991 3.24546 1.93078 0.00000 0.00001 SEMA3A 10371 1.81856 0.14036 0.00006 0.00172 SEMA5A 9037 1.87493 -0.88378 0.00037 0.00881 SEPT5 5413 1.61489 0.51764 0.00182 0.03460 SERPINB10 5273 4.74995 0.03390 0.00000 0.00000 SERPINB3 6317 3.40676 4.24964 0.00001 0.00050 SERPINF1 5176 0.86327 3.36454 0.00057 0.01273 SEZ6L2 26470 1.84160 -1.25027 0.00038 0.00893 SHANK2 22941 2.55518 -0.49263 0.00004 0.00137 SHFM1 7979 0.46284 5.23538 0.00069 0.01502 SIGLEC8 27181 1.50356 0.10614 0.00007 0.00195 SIX1 6495 3.58495 0.04747 0.00000 0.00005 SIX2 10736 4.47712 -0.75356 0.00000 0.00000 SIX4 51804 3.41360 0.41282 0.00000 0.00002 SIX5 147912 1.16705 -0.95987 0.00119 0.02413 SLC12A2 6558 0.94460 3.48495 0.00004 0.00129 SLC13A3 64849 3.77133 -0.79277 0.00000 0.00000 SLC16A9 220963 3.79902 0.79181 0.00000 0.00001 SLC22A16 85413 1.53042 0.70753 0.00017 0.00437 SLC22A23 63027 1.22073 2.40078 0.00185 0.03503 SLC23A1 9963 1.24308 -0.73067 0.00141 0.02801 SLC24A3 57419 1.14647 -0.23659 0.00046 0.01062 SLC25A4 291 1.76198 0.55591 0.00000 0.00002 SLC26A4 5172 3.09865 1.43367 0.00000 0.00002 SLC26A4-AS1 286002 2.96643 -1.36397 0.00042 0.00985 SLC27A2 11001 3.12035 1.25671 0.00000 0.00000 SLC29A4 222962 1.62418 -1.15988 0.00018 0.00465 SLC2A10 81031 3.76120 -0.02201 0.00000 0.00000 SLC2A12 154091 0.95396 0.16477 0.00032 0.00768 SLC34A2 10568 2.20525 1.83358 0.00004 0.00130 SLC44A3 126969 1.97066 -0.20961 0.00215 0.04014 SLC44A4 80736 3.29121 3.38231 0.00000 0.00000 SLC4A4 8671 3.54748 -0.17567 0.00000 0.00000 SLC52A1 55065 2.15769 -1.53682 0.00000 0.00004 SLC5A1 6523 2.16099 -0.25906 0.00238 0.04384 SLC5A8 160728 4.15547 1.23779 0.00000 0.00003 SLC6A9 6536 2.01403 -0.43776 0.00013 0.00346 SLC7A2 6542 3.37589 0.89090 0.00000 0.00004 SLC9A3 6550 2.08619 0.92098 0.00021 0.00526

E48 SLFN13 146857 0.75711 3.17656 0.00019 0.00494 SLITRK6 84189 3.98470 -0.49155 0.00000 0.00005 SLPI 6590 2.28381 6.44361 0.00000 0.00015 SMARCA1 6594 1.78650 -0.65262 0.00001 0.00045 SMIM22 440335 1.96713 0.40377 0.00023 0.00578 SMIM6 100130933 1.82989 -1.48022 0.00048 0.01097 SMPD3 55512 1.10232 1.96289 0.00008 0.00228 SNCA 6622 0.80770 2.63544 0.00224 0.04176 SNCAIP 9627 1.41123 -0.78626 0.00048 0.01097 SNHG5 387066 0.76512 5.02792 0.00088 0.01876 SNTN 132203 4.05344 1.86591 0.00000 0.00000 SOCS2 8835 0.85412 3.05717 0.00113 0.02313 SOX2 6657 4.07988 0.84181 0.00000 0.00000 SOX21 11166 4.08720 0.37143 0.00000 0.00003 SOX21-AS1 100507533 3.79722 -0.65776 0.00000 0.00004 SOX9 6662 2.08877 0.62624 0.00229 0.04232 SPA17 53340 0.96926 1.62595 0.00024 0.00597 SPAG16 79582 1.12622 1.51051 0.00000 0.00013 SPAG17 200162 3.37464 1.07633 0.00000 0.00000 SPAG6 9576 3.66958 1.51480 0.00000 0.00000 SPAG8 26206 1.52166 0.74118 0.00001 0.00028 SPATA17 128153 2.75852 -0.68974 0.00000 0.00001 SPATA18 132671 2.57297 2.08545 0.00000 0.00000 SPATA6L 55064 2.38977 -1.09622 0.00001 0.00028 SPDEF 25803 3.83532 1.39184 0.00000 0.00002 SPEF1 25876 2.76597 -0.18647 0.00000 0.00005 SPEF2 79925 1.53306 1.38100 0.00001 0.00027 SPNS3 201305 1.27455 0.51056 0.00206 0.03857 SPON2 10417 1.24100 -0.65691 0.00125 0.02522 SRD5A2 6716 3.68860 -1.04494 0.00000 0.00010 SRGAP3 9901 1.02319 1.24300 0.00055 0.01236 SRGAP3-AS2 100507660 3.85842 0.34778 0.00000 0.00000 ST6GALNAC1 55808 3.80477 1.67663 0.00000 0.00000 STEAP2 261729 2.95418 -1.29073 0.00004 0.00116 STK33 65975 3.39385 0.03306 0.00000 0.00001 STMND1 401236 4.07960 -0.74941 0.00000 0.00006 STOML3 161003 3.67084 0.08058 0.00000 0.00004 STOX1 219736 2.84028 -0.52185 0.00005 0.00147 STRA6 64220 2.89005 -1.29388 0.00000 0.00020 SUSD4 55061 1.91588 -1.26560 0.00016 0.00413 SVEP1 79987 2.23050 -0.59377 0.00000 0.00002 SYBU 55638 3.74868 0.27447 0.00000 0.00000 SYNM 23336 1.22071 -0.27181 0.00021 0.00530 SYTL2 54843 2.13071 3.04575 0.00000 0.00000 SYTL5 94122 2.94175 -0.42706 0.00002 0.00061 TACC2 10579 2.51280 1.50172 0.00003 0.00095 TBX1 6899 1.09670 -1.08114 0.00228 0.04231 TCTE1 202500 3.39738 -1.42510 0.00001 0.00025 TCTEX1D1 200132 2.63709 0.00551 0.00000 0.00012 TCTEX1D2 255758 1.44264 0.32548 0.00000 0.00005 TEKT1 83659 3.64217 0.91867 0.00000 0.00001 TEKT2 27285 2.75009 0.58458 0.00000 0.00002 TEKT4 150483 1.68950 -1.15528 0.00055 0.01244 TEX26 122046 4.12497 -1.09528 0.00002 0.00072 TEX9 374618 1.72927 -0.58359 0.00028 0.00694

E49 TFF1 7031 2.69173 -1.29702 0.00143 0.02826 TFF3 7033 3.59421 2.92171 0.00000 0.00000 THRB 7068 2.05745 0.06407 0.00004 0.00123 TIMP4 7079 1.35282 -0.36775 0.00001 0.00023 TLR3 7098 1.08901 0.60709 0.00132 0.02649 TMC4 147798 1.73298 2.53895 0.00021 0.00542 TMC5 79838 2.23050 3.28146 0.00012 0.00321 TMCC2 9911 1.37767 -0.59648 0.00052 0.01184 TMEM125 128218 3.27830 0.13611 0.00000 0.00001 TMEM184A 202915 1.72308 0.99486 0.00257 0.04671 TMEM190 147744 3.19899 0.89489 0.00000 0.00004 TMEM231 79583 1.42990 2.17973 0.00000 0.00000 TMEM232 642987 3.05942 -0.16413 0.00000 0.00000 TMEM30B 161291 2.75848 1.46050 0.00001 0.00044 TMEM67 91147 1.10816 1.77807 0.00016 0.00414 TMEM98 26022 3.70749 -0.51140 0.00000 0.00001 TMPRSS3 64699 2.19633 -0.34551 0.00000 0.00009 TMSB10 9168 0.49955 9.54379 0.00113 0.02315 TMSB10P1 100506723 0.55092 6.76125 0.00031 0.00762 TNFAIP8L1 126282 1.13570 2.99231 0.00000 0.00002 TNFRSF19 55504 4.03833 0.29321 0.00000 0.00000 TOM1L1 10040 1.55633 0.36406 0.00002 0.00067 TOMM34 10953 0.50996 4.26784 0.00061 0.01360 TOX3 27324 2.83758 -1.11377 0.00003 0.00096 TP73 7161 2.37376 -0.82408 0.00002 0.00058 TPM1 7168 0.53210 3.19832 0.00147 0.02905 TPPP3 51673 2.90819 3.00568 0.00000 0.00000 TPSAB1 7177 2.66992 1.92211 0.00005 0.00146 TPSB2 64499 2.70522 1.97391 0.00008 0.00225 TPSD1 23430 2.85461 -0.72398 0.00025 0.00612 TRABD2A 129293 0.82296 -0.16506 0.00154 0.03012 TREX1 11277 0.59575 4.11451 0.00200 0.03760 TRIM7 81786 1.36991 -0.16263 0.00007 0.00204 TRPV5 56302 -1.33843 -1.49287 0.00048 0.01095 TRPV6 55503 1.93068 -0.99560 0.00010 0.00280 TSGA10 80705 1.90048 0.31266 0.00000 0.00004 TSHZ2 128553 1.62193 0.21145 0.00055 0.01236 TSNAXIP1 55815 1.94892 0.05736 0.00002 0.00056 TSPAN1 10103 3.65816 4.84954 0.00000 0.00000 TSPAN11 441631 3.78235 -1.31227 0.00000 0.00002 TSPAN12 23554 1.29675 -0.23086 0.00032 0.00784 TSPAN13 27075 1.78903 3.83803 0.00000 0.00005 TSPAN18 90139 1.15838 -0.41995 0.00080 0.01737 TSPAN19 144448 4.25661 0.38357 0.00000 0.00002 TSPAN8 7103 4.79278 1.96958 0.00000 0.00000 TTC16 158248 2.64408 -0.58375 0.00000 0.00014 TTC25 83538 2.71417 0.25666 0.00000 0.00000 TTC26 79989 0.96286 0.85933 0.00061 0.01362 TTC29 83894 3.44110 -0.39129 0.00000 0.00003 TTC30A 92104 0.87454 1.33210 0.00104 0.02154 TTC39A 22996 2.29234 0.47442 0.00000 0.00014 TTLL10 254173 2.47785 0.25048 0.00000 0.00008 TTLL10-AS1 100506376 3.34449 -1.58376 0.00000 0.00000 TTLL7 79739 1.96253 -1.29085 0.00001 0.00025 TTLL9 164395 1.77843 -1.12327 0.00015 0.00406

E50 TUB 7275 2.64543 -0.58712 0.00000 0.00005 TUBA4B 80086 1.79875 1.00912 0.00046 0.01072 TUSC3 7991 3.65216 0.46311 0.00000 0.00011 UAP1 6675 0.49562 4.88663 0.00151 0.02968 UBFD1 56061 0.38032 4.05785 0.00229 0.04232 UBXN10 127733 1.40647 1.92726 0.00010 0.00280 UGT2A1 10941 4.60063 0.88391 0.00000 0.00010 UNC119B 84747 0.73131 3.04391 0.00006 0.00166 UPK1B 7348 3.96264 2.54362 0.00000 0.00002 URB1-AS1 84996 0.66619 0.17061 0.00264 0.04771 USP41 373856 1.06235 0.49678 0.00131 0.02648 VANGL2 57216 2.11568 -0.43744 0.00017 0.00449 VIPR1 7433 1.45531 -0.32568 0.00219 0.04076 VSIG1 340547 1.52404 -1.26701 0.00102 0.02130 VSTM1 284415 1.77192 0.54687 0.00069 0.01502 VSTM2L 128434 3.48058 -0.13354 0.00000 0.00000 VTCN1 79679 2.66284 -0.06821 0.00001 0.00049 VWA3A 146177 2.65694 1.26141 0.00002 0.00057 VWA3B 200403 4.03130 0.85052 0.00000 0.00000 WBSCR22 114049 0.37893 4.62529 0.00130 0.02624 WDR31 114987 1.36714 -0.83973 0.00147 0.02902 WDR38 401551 2.56206 0.72872 0.00001 0.00025 WDR54 84058 1.26701 1.54561 0.00000 0.00009 WDR63 126820 2.58057 0.20703 0.00000 0.00000 WDR66 144406 3.20755 1.38558 0.00000 0.00000 WDR78 79819 3.36151 0.94791 0.00000 0.00000 WDR86-AS1 100131176 2.63447 -0.41794 0.00000 0.00003 WDR93 56964 2.60325 -1.43670 0.00001 0.00042 WFDC2 10406 2.67281 5.10316 0.00004 0.00116 WFDC6 140870 3.19115 -1.41508 0.00000 0.00016 WISP1 8840 -2.82717 0.23703 0.00110 0.02265 WNK2 65268 2.29521 -0.23776 0.00003 0.00092 WNT5A 7474 1.57671 1.47436 0.00080 0.01733 ZBBX 79740 3.68854 0.72413 0.00000 0.00001 ZC2HC1C 79696 1.37490 -0.23354 0.00000 0.00011 ZDHHC1 29800 1.35399 0.25718 0.00000 0.00015 ZFAT 57623 1.10770 3.17564 0.00003 0.00100 ZMYND10 51364 2.51887 2.03092 0.00000 0.00000 ZMYND12 84217 0.91976 0.55697 0.00253 0.04601 ZNF204P 7754 1.93116 -0.13842 0.00001 0.00035 ZNF214 7761 1.53430 -0.59635 0.00113 0.02315 ZNF474 133923 2.65422 -0.65249 0.00000 0.00001 ZNF704 619279 1.37166 0.04001 0.00002 0.00073 ZNF750 79755 2.40165 0.79450 0.00015 0.00403 ZNF853 54753 1.50804 -1.35054 0.00039 0.00915

E51 Table E5. Gene ontology biological processes associated with the set of genes that are networked around the hubs. Data analysis was performed with Enrichr software (E17).

Hub Interacting genes Function Adjusted (No. genes) p-value EGFR ACTA2, AP1M2, ARFGEF3, BDKRB2, C9orf3, positive regulation of MAPK cascade 2.62E-05 (n=73) CARS2, CAV2, CBLC, CD2AP, CDH1, CLU, (GO:0043410) COL1A1, CTGF, CTNNA1, CTTN, CX3CL1, CYBB, epithelial cell development (GO:0002064) 1.01E-04 CYP2J2, DAG1, DSG2, DUOX1, DUSP3, EFNA1, positive regulation of kinase activity 3.45E-04 EGFR, EPS8, ERBB2, FASN, FBLIM1, FGFR2, (GO:0033674) GLIPR2, GPBAR1, HDC, HMGB3, IGFBP3, IL13, regulation of epithelial cell proliferation 4.54E-04 IL33, ITGB4, KITLG, LAMC2, LSR, MAPK8IP1, (GO:0050678) MAPKAPK3, MS4A2, MST1R, MYO1B, MYO1D, ERBB signaling pathway (GO:0038127) 1.87E-03 NFIB, NOS2, NTRK1, NTS, PBX1, PIK3R3, PLCE1, epidermal growth factor receptor POSTN, PTPN21, PTPRF, PTPRK, RUSC1, SCD5, signaling pathway (GO:0007173) 1.87E-03 SLC12A2, SLC5A1, SOX9, SPDEF, SPTLC1, STX6, TFAP2A, TLR3, TOM1L1, TP63, TPP1, TRPV1, TUBB4B, YES1, YWHAB ERBB2 ACTA2, AGR2, AP1M2, CCDC80, CCND3, CDH1, regulation of cell adhesion (GO:0030155) 1.19E-03 (n=65) CDH3, CHST10, CLDN3, CLDN4, CLU, COL1A1, glandular epithelial cell differentiation 1.31E-03 CTGF, CTTN, CYP2J2, DAG1, DECR1, DSG2, (GO:0002067) EFNA1, EGFR, EPHX2, EPPK1, ERBB2, FASN, lung epithelial cell differentiation 3.33E-03 FGFR2, FOXA1, FSTL1, FXYD3, GNAI1, HOMER2, (GO:0060487) IGFBP3, IL1RL1, IRF6, ITGB4, LAMA3, LAMC2, extracellular matrix organization 4.56E-03 LAMP1, LSR, MAPK8IP1, MATK, MFNG, MSMB, (GO:0030198) MUC13, NET1, NFIB, NOS2, NRG4, NTRK1, lung secretory cell differentiation 5.25E-03 PBX1, PDLIM4, PIK3R3, PLOD2, PLXNB1, PODXL, (GO:0061140) PPP2R5A, PRR15L, PTPRK, PTPRZ1, SDPR, SPDEF, SQLE, ST3GAL6, STRBP, TFAP2A, TPD52, USF2 CDH1 ACTA2, AJUBA, AMOT, ANK3, AZGP1, C9orf3, cell junction organization (GO:0034330) 2.86E-06 (n=56) CCL17, CDC42EP5, CDH1, CDH3, CFTR, CLCA2, cell junction assembly (GO:0034329) 1.16E-04 CLDN1, CLDN3, CLDN4, CTNNA1, DDR1, single organismal cell-cell adhesion 1.29E-04 DNAJB4, EGFR, ERBB2, ESRP2, FOXA1, GLIPR2, (GO:0016337) GRHL2, ID4, IGFBP3, IL5, IL13, ITGB6, KRT8, epithelial cell development (GO:0002064) 9.29E-04 LOX, MAGI1, MAPKAPK3, MEIS2, MST1R, positive regulation of cell migration 1.95E-03 MUC16, OCLN, PBX1, PKP2, PKP4, PLEKHA7, (GO:0030335) PODXL, POSTN, PRKAA2, PTPRF, PTPRU, morphogenesis of an epithelium 2.22E-03 RAP1GAP, RRAS2, SEMA3A, SIX1, SLC9A3R2, (GO:0002009) SOX9, SPDEF, TFAP2A, TPBG, YES1, ZFYVE9 IL13 ALOX15, CCL17, CCL26, CD209, CD1A, CD1B, positive regulation of inflammatory 6.16E-04 (n=48) CD1C, CD1E, CD200R1, CD300LF, CDH1, CFI, response (GO:0050729) CHN2, COL1A1, CTGF, CTNNAL1, CX3CL1, CYBB, positive regulation of macrophage 1.97E-03 DUOX1, EGFR, FCER1A, FOXA3, G6PD, GATA1, activation (GO:0043032) GATA2, HDC, HOMER2, IL5, IL13, IL33, IL1RL1, cellular response to cytokine stimulus 2.70E-03 KITLG, MAPK10, MATK, MUC2, NOS2, NTN1, (GO:0071345) POSTN, SERPINA1, SERPINB3, SERPINB4, positive regulation of defense response 3.66E-03 SERPINB5, SLC26A4, SPDEF, ST3GAL6, STXBP1, (GO:0031349) TLR3, TPSAB1/TPSB2, TRPV1 positive regulation of immune effector 6.59E-03 process (GO:0002699)

E52 Table E6. Multiplex literature mining was performed for the genes associated with the four dominant hubs (EGFR, ERBB2, CDH1 and IL13) in the merged module. The literature search was performed with Pubmatrix software (E18).

E54

Gene Symbol EGFR ERBB2 CDH1 IL13 Asthma Wheeze Airways hyperreactivity Airways remodeling Mucous Atopy Allergen Th2 Lung development Epithelium TOTAL ACTA2 ACTA2 ACTA2 ACTA2 13 0 0 3 4 0 2 4 26 110 162

AGR2 AGR2 8 0 0 0 19 0 4 1 5 20 57

AJUBA AJUBA 0 0 0 0 0 0 0 0 3 2 5

ALOX15 ALOX15 61 0 0 1 9 1 7 22 13 109 223

AMOT AMOT 0 0 0 0 0 0 0 0 1 11 12

ANK3 ANK3 0 0 0 0 0 0 0 0 0 2 2

AP1M2 AP1M2 AP1M2 0 0 0 0 0 0 0 0 1 1 2

ARFGEF3 ARFGEF3 0 0 0 0 0 0 0 0 0 0 0

AZGP1 AZGP1 1 0 0 0 1 0 0 0 0 7 9

BDKRB2 BDKRB2 74 1 7 1 12 0 18 0 10 235 358

C9orf3 C9orf3 C9orf3 0 0 0 0 0 0 0 0 0 0 0

CARS2 CARS2 0 0 0 0 0 0 0 0 0 0 0

CAV2 CAV2 1 0 0 0 0 0 0 0 5 8 14

CBLC CBLC 0 0 0 0 0 0 0 0 0 4 4

CCDC80 CCDC80 0 0 0 0 0 0 0 0 0 2 2

CCL17 CCL17 CCL17 143 1 5 1 15 13 106 316 40 48 688

CCL26 CCL26 64 0 0 1 6 3 16 65 12 37 204

E55 CCND3 CCND3 0 0 0 0 1 0 0 0 4 18 23

CD1A CD1A 34 0 0 0 36 16 68 83 17 372 626

CD1B CD1B 1 0 0 0 1 0 1 13 1 17 34

CD1C CD1C 17 0 0 0 3 3 14 33 5 29 104

CD1E CD1E 1 0 0 0 0 0 1 0 0 0 2

CD200R1 CD200R1 0 0 0 0 1 0 1 6 1 5 14

CD209 CD209 3 0 0 0 3 0 2 18 0 11 37

CD2AP CD2AP 0 0 0 0 0 0 0 0 1 17 18

CD300LF CD300LF 0 0 0 0 0 1 0 0 0 0 1

CDC42EP5 CDC42EP5 0 0 0 0 0 0 0 0 0 1 1

CDH1 CDH1 CDH1 CDH1 CDH1 5 0 0 0 3 1 0 1 20 85 115

CDH3 CDH3 CDH3 0 0 0 0 1 0 0 0 4 15 20

CFI CFI 5 0 0 0 1 0 0 0 5 12 23

CFTR CFTR 88 2 1 10 325 3 10 11 252 1022 1724

CHN2 CHN2 0 0 0 0 0 0 0 0 0 3 3

CHST10 CHST10 0 0 0 0 0 0 0 1 1 1 3

CLCA2 CLCA2 0 0 0 0 1 0 0 0 2 14 17

CLDN1 CLDN1 9 0 0 1 14 2 14 9 13 354 416

CLDN3 CLDN3 CLDN3 0 0 0 0 3 0 0 0 3 72 78

CLDN4 CLDN4 CLDN4 2 0 0 0 4 0 1 5 4 89 105

CLU CLU CLU 2 0 0 0 4 0 1 1 5 85 98

E56 COL1A1 COL1A1 COL1A1 COL1A1 5 0 0 0 0 0 1 2 16 20 44

CTGF CTGF CTGF CTGF 23 0 0 4 4 0 1 7 76 204 319

CTNNA1 CTNNA1 CTNNA1 1 0 0 0 2 0 0 0 3 78 84

CTNNAL1 CTNNAL1 2 0 0 0 0 0 0 0 0 1 3

CTTN CTTN CTTN 2 0 0 0 1 0 0 0 3 37 43

CX3CL1 CX3CL1 CX3CL1 19 0 0 0 5 1 7 19 19 97 167

CYBB CYBB CYBB 12 0 0 0 2 0 0 4 19 131 168

CYP2J2 CYP2J2 CYP2J2 1 0 0 0 0 0 0 0 4 27 32

DAG1 DAG1 DAG1 0 0 0 0 0 0 0 0 2 35 37

DDR1 DDR1 3 0 0 0 0 1 0 0 16 21 41

DECR1 DECR1 0 0 0 0 0 0 0 0 0 0 0

DNAJB4 DNAJB4 0 0 0 0 0 0 1 0 2 2 5

DSG2 DSG2 DSG2 1 0 0 0 2 0 0 1 0 25 29

DUOX1 DUOX1 DUOX1 6 0 0 0 8 0 1 9 6 38 68

DUSP3 DUSP3 0 0 0 0 0 0 0 0 0 0 0

EFNA1 EFNA1 EFNA1 0 0 0 0 0 0 0 0 3 2 5

EGFR EGFR EGFR EGFR EGFR 112 0 1 9 161 5 20 23 1238 1127 2696

EPHX2 EPHX2 1 0 0 0 0 0 0 1 2 7 11

EPPK1 EPPK1 0 0 0 0 0 0 0 0 0 2 2

EPS8 EPS8 0 0 0 0 0 0 0 0 0 16 16

ERBB2 ERBB2 ERBB2 ERBB2 7 0 0 0 24 0 1 28 257 628 945

E57 ESRP2 ESRP2 0 0 0 0 0 0 0 0 0 2 2

FASN FASN FASN 0 0 0 0 1 0 0 1 4 15 21

FBLIM1 FBLIM1 0 0 0 0 0 0 0 0 1 1 2

FCER1A FCER1A 22 0 0 0 3 16 11 3 3 0 58

FGFR2 FGFR2 FGFR2 0 0 1 0 7 1 1 1 60 273 344

FOXA1 FOXA1 FOXA1 2 0 0 0 3 0 1 0 21 61 88

FOXA3 FOXA3 5 0 0 0 7 0 3 3 5 9 32

FSTL1 FSTL1 0 0 0 0 0 0 0 0 7 4 11

FXYD3 FXYD3 0 0 0 0 3 0 0 0 0 0 3

G6PD G6PD 13 0 0 0 7 1 2 1 12 48 84

GATA1 GATA1 11 0 1 1 2 10 3 12 6 23 69

GATA2 GATA2 9 0 0 1 1 5 1 14 5 45 81

GLIPR2 GLIPR2 GLIPR2 0 0 0 0 0 0 1 0 0 1 2

GNAI1 GNAI1 0 0 0 0 0 0 0 0 0 1 1

GPBAR1 GPBAR1 0 0 0 0 1 0 0 0 1 3 5

GRHL2 GRHL2 1 0 0 1 0 0 0 0 3 11 16

HDC HDC HDC 14 0 0 0 7 0 6 20 15 27 89

HMGB3 HMGB3 0 0 0 0 0 0 0 0 1 0 1

HOMER2 HOMER2 HOMER2 0 0 0 0 0 0 0 0 0 0 0

ID4 ID4 0 1 0 0 0 0 0 1 3 13 18

IGFBP3 IGFBP3 IGFBP3 IGFBP3 13 2 0 0 3 0 3 3 43 155 222

E58 IL13 IL13 IL13 IL13 1329 18 74 36 319 130 593 1564 279 250 4592

IL1RL1 IL1RL1 IL1RL1 91 1 3 4 6 8 29 143 22 19 326

IL33 IL33 IL33 104 2 2 2 6 6 30 158 18 42 370

IL5 IL5 IL5 118 3 5 0 11 7 56 165 15 12 392

IRF6 IRF6 0 0 0 0 1 0 0 0 1 14 16

ITGB4 ITGB4 ITGB4 7 0 0 0 32 1 1 2 12 242 297

ITGB6 ITGB6 0 0 0 0 0 0 0 0 4 3 7

KITLG KITLG KITLG 179 2 6 7 99 13 72 239 450 3055 4122

KRT8 KRT8 0 0 0 0 1 0 0 0 1 31 33

LAMA3 LAMA3 0 0 0 0 5 0 0 0 2 14 21

LAMC2 LAMC2 LAMC2 0 0 0 0 9 0 0 0 4 54 67

LAMP1 LAMP1 1 0 0 0 1 0 1 2 2 28 35

LOX LOX 64 0 0 2 20 0 8 29 59 375 557

LSR LSR LSR 3 0 0 0 1 1 3 2 3 4 17

MAGI1 MAGI1 0 0 0 0 0 0 0 0 1 4 5

MAPK10 MAPK10 0 0 0 0 0 0 0 0 1 0 1

MAPK8IP1 MAPK8IP1 MAPK8IP1 0 0 0 0 0 0 0 0 0 2 2

MAPKAPK3 MAPKAPK3 MAPKAPK3 0 0 0 0 0 0 0 0 2 1 3

MATK MATK MATK 0 0 0 0 0 0 0 1 1 1 3

MEIS2 MEIS2 0 0 0 0 0 0 0 0 0 7 7

MFNG MFNG 1 0 0 0 0 0 0 1 0 2 4

E59 MS4A2 MS4A2 31 2 0 0 0 14 10 3 1 0 61

MSMB MSMB 0 0 0 0 0 0 0 0 1 3 4

MST1R MST1R MST1R 0 0 0 0 0 0 0 0 2 2 4

MUC13 MUC13 0 0 0 0 6 0 0 0 0 12 18

MUC16 MUC16 2 0 0 0 18 0 1 0 4 62 87

MUC2 MUC2 34 1 2 0 423 0 2 16 14 378 870

MYO1B MYO1B 0 0 0 0 0 0 0 0 0 1 1

MYO1D MYO1D 0 0 0 0 0 0 0 0 0 0 0

NET1 NET1 0 0 0 0 0 0 0 0 0 3 3

NFIB NFIB NFIB 0 0 0 0 0 0 0 0 10 9 19

NOS2 NOS2 NOS2 NOS2 138 1 11 4 57 7 34 121 117 738 1228

NRG4 NRG4 0 0 0 0 0 0 0 0 0 3 3

NTN1 NTN1 0 0 0 0 1 0 0 0 1 1 3

NTRK1 NTRK1 NTRK1 1 0 0 0 0 0 0 0 2 2 5

NTS NTS 24 5 1 1 5 0 10 5 13 47 111

OCLN OCLN 5 0 0 1 14 0 8 1 7 432 468

PBX1 PBX1 PBX1 PBX1 0 0 0 0 0 0 0 0 6 14 20

PDLIM4 PDLIM4 7 0 0 0 3 1 0 6 52 347 416

PIK3R3 PIK3R3 PIK3R3 0 0 0 0 0 0 0 0 0 0 0

PKP2 PKP2 0 0 0 0 0 0 1 0 0 12 13

PKP4 PKP4 0 0 0 0 0 0 0 0 0 5 5

E60 PLCE1 PLCE1 0 0 0 0 0 0 0 1 1 0 2

PLEKHA7 PLEKHA7 0 0 0 0 0 0 0 0 0 4 4

PLOD2 PLOD2 0 0 0 0 0 0 0 0 1 2 3

PLXNB1 PLXNB1 0 0 0 0 0 0 0 0 4 12 16

PODXL PODXL PODXL 0 0 0 0 0 0 0 0 4 4 8

POSTN POSTN POSTN POSTN 46 0 1 4 6 2 8 23 20 36 146

PPP2R5A PPP2R5A 0 0 0 0 0 0 0 0 0 0 0

PRKAA2 PRKAA2 0 0 0 0 0 0 0 0 0 8 8

PRR15L PRR15L 0 0 0 0 0 0 0 0 0 0 0

PTPN21 PTPN21 0 0 0 0 1 0 0 0 0 0 1

PTPRF PTPRF PTPRF 1 0 0 0 0 0 0 0 8 18 27

PTPRK PTPRK PTPRK 0 0 0 0 0 0 0 0 2 2 4

PTPRU PTPRU 0 0 0 0 0 0 0 0 1 3 4

PTPRZ1 PTPRZ1 0 0 0 0 0 0 0 0 0 4 4

RAP1GAP RAP1GAP 1 0 0 0 0 0 1 0 0 3 5

RRAS2 RRAS2 1 0 0 0 0 0 0 0 0 2 3

RUSC1 RUSC1 0 0 0 0 0 0 0 0 0 0 0

SCD5 SCD5 0 0 0 0 0 0 0 0 0 0 0

SDPR SDPR 0 0 0 0 0 0 0 0 0 1 1

SEMA3A SEMA3A 3 0 0 0 0 1 0 3 10 65 82

SERPINA1 SERPINA1 9 0 0 0 2 1 2 0 16 7 37

E61 SERPINB3 SERPINB3 5 0 0 0 1 0 3 2 0 8 19

SERPINB4 SERPINB4 3 0 0 0 1 0 3 1 0 3 11

SERPINB5 SERPINB5 0 0 0 0 1 0 0 0 1 5 7

SIX1 SIX1 0 0 0 0 0 0 0 0 4 34 38

SLC12A2 SLC12A2 1 0 0 0 3 0 1 0 4 37 46

SLC26A4 SLC26A4 14 0 0 0 8 0 2 3 6 24 57

SLC5A1 SLC5A1 0 0 0 0 0 0 0 0 0 28 28

SLC9A3R2 SLC9A3R2 0 0 0 0 0 0 0 0 0 1 1

SOX9 SOX9 SOX9 0 0 0 0 4 0 0 0 31 176 211

SPDEF SPDEF SPDEF SPDEF SPDEF 14 0 0 1 25 0 8 9 6 29 92

SPTLC1 SPTLC1 1 0 0 0 0 0 0 0 0 1 2

SQLE SQLE 0 0 0 0 0 0 0 0 0 0 0

ST3GAL6 ST3GAL6 ST3GAL6 0 0 0 0 1 0 0 1 0 0 2

STRBP STRBP 0 0 0 0 0 0 0 0 0 1 1

STX6 STX6 0 0 0 0 0 0 0 0 0 0 0

STXBP1 STXBP1 0 0 0 0 0 0 0 0 0 1 1

TFAP2A TFAP2A TFAP2A TFAP2A 2 0 0 0 1 0 0 0 12 91 106

TLR3 TLR3 TLR3 90 2 3 2 22 9 19 73 42 127 389

TOM1L1 TOM1L1 0 0 0 0 0 0 0 0 0 4 4

TP63 TP63 1 0 0 0 8 0 0 1 27 208 245

TPBG TPBG 0 0 0 0 0 0 0 0 0 1 1

E62 TPD52 TPD52 0 0 0 0 0 0 0 0 2 2 4

TPP1 TPP1 1 0 0 0 0 0 1 0 1 3 6

TPSAB1/ TPSAB1/ 1 0 0 0 0 0 0 0 0 0 1 TPSB2 TPSB2

TRPV1 TRPV1 TRPV1 81 2 7 2 33 2 21 6 15 159 328

TUBB4B TUBB4B 0 0 0 0 0 0 0 0 0 0 0

USF2 USF2 2 0 0 0 0 0 1 0 0 5 8

YES1 YES1 YES1 1 0 0 0 0 0 0 0 0 9 10

YWHAB YWHAB 2 0 0 0 0 0 0 0 0 1 3

ZFYVE9 ZFYVE9 0 0 0 0 0 0 0 0 0 0 0

E63 Table E7. Gene ontology cellular components associated with genes from the CDHR3-associated mucociliary clearance module. Data analysis was performed with Enrichr software (E17).

Adjusted P- Term Overlap P-value value ciliary part (GO:0044441) 41/223 < 1E-14 < 1E-14 cilium (GO:0005929) 42/243 < 1E-14 < 1E-14 motile cilium (GO:0031514) 20/68 < 1E-14 2E-14 axoneme (GO:0005930) 17/48 < 1E-14 1.9E-13 dynein complex (GO:0030286) 14/39 8.40E-13 3.54E-11 microtubule (GO:0005874) 33/360 9.20E-13 3.54E-11 axoneme part (GO:0044447) 11/26 6.03E-11 1.99E-09 axonemal dynein complex (GO:0005858) 8/12 1.76E-09 5.07E-08 microtubule associated complex (GO:0005875) 17/138 7.46E-09 1.91E-07 cytoplasmic dynein complex (GO:0005868) 9/25 1.10E-08 2.53E-07 ciliary transition zone (GO:0035869) 5/13 1.78E-05 3.74E-04 sperm part (GO:0097223) 10/103 6.45E-05 1.24E-03 ciliary basal body (GO:0036064) 8/71 1.36E-04 2.42E-03 primary cilium (GO:0072372) 9/99 2.36E-04 3.90E-03 sperm flagellum (GO:0036126) 4/13 2.63E-04 4.05E-03 sperm midpiece (GO:0097225) 3/10 1.75E-03 2.53E-02 photoreceptor connecting cilium (GO:0032391) 4/25 2.19E-03 2.97E-02 nonmotile primary cilium (GO:0031513) 6/67 2.79E-03 3.59E-02 cytoplasmic microtubule (GO:0005881) 5/58 7.23E-03 8.79E-02 intraciliary transport particle B (GO:0030992) 3/20 9.41E-03 1.09E-01

Table E8. Characteristics of the study population.

INOS number Phenotype Gender Age HDM 135 atopic asthmatic f 7.93 Y, 139 atopic asthmatic f 4.24 Y, > 100 kU/L 158 atopic asthmatic m 4.02 Y, 16.2 kU/L 164 atopic asthmatic f 10.42 Y, 73.3 kU/L 165 atopic asthmatic m 5.44 Y, >100 kU/L 168 atopic asthmatic m 5.45 Y, 19.3 kU/L 171 atopic asthmatic f 11.90 Y, 22.0Ku/L 187 atopic asthmatic m 6.85 Y, 26.2 kU/L 156 nonatopic control f 5.01 N 160 nonatopic control m 13.84 N 162 nonatopic control f 7.10 N 167 nonatopic control f 5.21 N 173 nonatopic control f 7.55 N 178 nonatopic control f 5.34 N 179 nonatopic control f 4.58 N 219 nonatopic control m 9.56 N

E63