Potential Role Vasculogenesis in Lupus Are Mediated

The Detrimental Effects of IFN-α on Vasculogenesis in Lupus Are Mediated by Repression of IL-1 Pathways: Potential Role in Atherogenesis and Renal Vascular This information is current as Rarefaction of September 29, 2021. Seth G. Thacker, Celine C. Berthier, Deborah Mattinzoli, Maria Pia Rastaldi, Matthias Kretzler and Mariana J. Kaplan J Immunol 2010; 185:4457-4469; Prepublished online 30 August 2010; Downloaded from doi: 10.4049/jimmunol.1001782 http://www.jimmunol.org/content/185/7/4457 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2010/08/30/jimmunol.100178 Material 2.DC1 References This article cites 131 articles, 44 of which you can access for free at: http://www.jimmunol.org/content/185/7/4457.full#ref-list-1

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The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2010 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology

The Detrimental Effects of IFN-a on Vasculogenesis in Lupus Are Mediated by Repression of IL-1 Pathways: Potential Role in Atherogenesis and Renal Vascular Rarefaction

Seth G. Thacker,*,1 Celine C. Berthier,†,1 Deborah Mattinzoli,‡ Maria Pia Rastaldi,‡ Matthias Kretzler,† and Mariana J. Kaplan*

Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that IFN-a plays a crucial role in premature vascular damage in SLE. IFN-a alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). In this study, we demonstrate that IFN-a promotes an antiangiogenic signature in

SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1a and b, IL-1R1, and vascular endothelial Downloaded from growth factor A, and upregulation of IL-1R antagonist and the decoy receptor IL-1R2. IL-1b promotes signiﬁcant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-a. The beneﬁcial effects from IL-1 are mediated, at least in part, by increases in EPC/CAC proliferation, by decreases in EPC/CAC apoptosis, and by preventing the skewing of CACs toward nonangiogenic pathways. IFN-a induces STAT2 and 6 phosphorylation in EPCs/CACs, and JAK inhibition abrogates the transcriptional antiangiogenic changes induced by IFN-a in these cells. Immunohistochemistry of renal biopsies from patients with lupus nephritis, but not anti-neutrophil cytoplasmic Ab-positive vasculitis, showed this pathway to be http://www.jimmunol.org/ operational in vivo, with increased IL-1R antagonist, downregulation of vascular endothelial growth factor A, and glomerular and blood vessel decreased capillary density, compared with controls. Our study introduces a novel putative pathway by which type I IFNs may interfere with vascular repair in SLE through repression of IL-1–dependent pathways. This could promote atherosclerosis and loss of renal function in this disease. The Journal of Immunology, 2010, 185: 4457–4469.

ystemic lupus erythematosus (SLE) is an autoimmune dis- end-stage disease. Although this manifestation can be the result of ease that primarily affects women of childbearing age (1). A earlier unchecked inflammation, alternative mechanisms media- S significant proportion of patients with lupus develops renal ting progressive loss of renal function may be envisioned, and the by guest on September 29, 2021 disease. In addition to inflammatory nephritis, renal involvement precise relationship between acute inflammatory and chronic fi- in lupus can manifest as a fibrotic, atrophic nephropathy with sig- brotic nephropathy remains unclear (2, 3). nificant renal functional impairment and potential progression to Furthermore, SLE is characterized by strikingly higher rates of premature atherosclerotic cardiovascular (CV) disease (4–7) not explained by Framingham risk factors (6, 8, 9). Whereas immune *Division of Rheumatology and †Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109; and dysregulation may play the dominant role in atherogenesis (10), ‡Renal Research Laboratory, Fondazione Istituto di Ricovero e Cura a Carattere the exact mechanisms leading to enhanced CV risk in lupus re- Scientifico Ospedale Maggiore Policlinico, Fondazione D’Amico per la Ricerca sulle Malattie Renali, Milan, Italy main to be determined. Our group previously reported that SLE 1 patients without traditional CV risk factors display a striking S.G.T. and C.C.B. contributed equally to this work and share first authorship. imbalance between endothelial cell damage and repair. This is Received for publication May 28, 2010. Accepted for publication July 30, 2010. manifested by an increase in circulating apoptotic endothelial cells This work was supported by the Lupus Foundation of America, the National Insti- tutes of Health through Public Health Service (Grant HL088419), and the Anthony S. uncoupled from proper endothelial repair, as shown by a significant Gramer Fund in Inflammation Research. This work was also supported in part by the decrease in the numbers and function of bone marrow-derived National Institutes of Health through the University of Michigan’s Cancer Center endothelial progenitor cells (EPCs) and myeloid circulating an- Support (Grant P30 CA46592), the Rheumatic Disease Core Center (Grant P30 AR48310), and the Applied Systems Biology Core in the O’Brien Renal Center giogenic cells (CACs) (11, 12). High levels of circulating apoptotic (Grant P30 DK081943). C.C.B. was supported by a National Kidney Foundation endothelial cells in SLE strongly correlate with endothelial dys- Post-Doctoral Fellowship. function (12), a surrogate marker of future atherosclerosis develop- Address correspondence and reprint requests to Dr. Mariana J. Kaplan, Division of ment (13). Additional studies have also reported aberrant pheno- Rheumatology, Department of Internal Medicine, University of Michigan Medical School, 1150 West Medical Center Drive, 5520 Medical Science Research Building-I, type and function of lupus EPCs/CACs in SLE patients (14). Ann Arbor, MI 48109-5680. E-mail address: [email protected] Type I IFNs, particularly IFN-a, have been proposed to play The online version of this article contains supplemental material. major pathogenic roles in SLE (15, 16). However, the possibility Abbreviations used in this paper: ANCA, anti-neutrophil cytoplasmic Ab; CAC, cir- that they may play a prominent role in premature vascular damage in culating angiogenic cell; CV, cardiovascular; DC, dendritic cell; ELAV, embryonic SLE had not been systematically investigated. Our group previously lethal, abnormal vision; EPC, endothelial progenitor cell; HIF, hypoxia-inducible fac- a tor; IL-1RN, IL-1R antagonist; LDL, low-density lipoprotein; N/A, not expressed reported that IFN- induces EPC/CAC apoptosis and skews mye- above the Affymetrix control baseline; SIGN, dendritic cell-specific intercellular ad- loid cells away from CACs and toward nonangiogenic phenotypes, hesion molecule-3–grabbing nonintegrin; SLE, systemic lupus erythematosus; UEA-1, including mature dendritic cells (DCs) (11). Importantly, neu- Ulex europaeus agglutinin-1; VEGF, vascular endothelial growth factor. tralization of type I IFN pathways restores normal EPC/CAC phe- Copyright Ó 2010 by The American Association of Immunologists, Inc. 0022-1767/10/$16.00 notype and function in SLE (11). Furthermore, the New Zealand www.jimmunol.org/cgi/doi/10.4049/jimmunol.1001782 4458 EFFECTS OF IFN-a ON VASCULOGENESIS IN LUPUS

Black/New Zealand White F1 murine model of lupus, a mouse strain quantify mature endothelial cells, which were considered as those that in which type I IFNs are considered to play a prominent role in coexpress UEA-1 and acetylated LDL. Images were acquired with an 3 pathogenesis (17–20), is also characterized by endothelial dys- original total magnification 100. The numeric aperture for the objective lens of the fluorescent microscope was 0.3. Images were acquired with an function and aberrant EPC phenotype and function (21–23). All Olympus DP30BW camera (Olympus, Tokyo, Japan) using the acquisition these observations support a potential role for type I IFNs in the software Olympus-BSW (Olympus). Final processing was done with development of premature atherosclerosis and altered vasculogen- Adobe Photoshop CS2 (San Jose, CA). esis in SLE. Phosphorylated STAT detection and inhibition of IFN-a In murine and human systems, EPCs and CACs appear to be signaling pathways crucial in vasculogenesis and angiogenesis (24–28). Decreases in EPC/CAC numbers and function in disease states associated to EPCs/CACs were cultured under proangiogenic stimulation, as stated above for 60 h, and then media was harvested and changed to endothelial cell enhanced vascular complications correlate with an increased risk growth medium without 20% FBS. After overnight incubation in serum- of atherosclerosis and vascular events (29–31). Whereas type I reduced media, cells were stimulated with 1000 IU IFN-a for 30 min, IFNs have been implicated in the progression of SLE (32), in the followed by fixation with 4% paraformaldehyde. Cells were permeabilized severity of lupus nephritis, and in the alteration of endothelial cell with 90% methanol and incubated with anti-pSTAT2 FITC (R&D Systems, repair (11, 14), the molecular pathways by which they mediate these Minneapolis, MN), and anti-pSTAT6 FITC (Cell Signaling Technology, Danvers, MA). Immunofluorescence was acquired using FACSCalibur (BD antiangiogenic effects have not been well characterized, and studies Biosciences, Bedford, MA), followed by analysis with FlowJo (Tree Star, have primarily focused on cancer cell lines (33–40). This study Ashland, OR). investigated the molecular pathways that are affected in EPCs/ To inhibit IFN-a signaling, the pan-JAK inhibitor 2-(1,1-dimethylethyl)-

CACs by IFN-a exposure and further assessed the mechanisms 9-ﬂuoro-3,6-dihydro-7H-benz[h]-imidaz[4,5-f]isoquinolin-7-1 (pyridone 6) Downloaded from or the PI3K inhibitor (5-(4-ﬂuoro-2-hydroxyphenyl)furan-2-ylmethylene) by which this molecule interferes with vasculogenesis in SLE. thiazolidine-2,4-dione were used (Calbiochem, Gibbstown, NJ). In brief, human EPCs/CACs were cultured under proangiogenic stimulation for 72 h, Materials and Methods followed by change of media containing 50 mm pyridone 6, 50 nm PI3K Patient selection inhibitor, or vehicle (DMSO) for 1 h before addition of 1000 U rIFN-a. EPCs/ CACs were incubated for additional 6 h, and then total RNA was isolated. The University of Michigan institutional review board approved this study.

Subjects gave informed consent in accordance with the Declaration of RNA isolation http://www.jimmunol.org/ Helsinki. To obtain peripheral blood, patients fulfilled the revised American College of Rheumatology criteria for SLE (41) and were enrolled from the Total RNA was isolated with Tripure (Roche, Indianapolis, IN), following University of Michigan outpatient rheumatology clinic. Age- and gender- the manufacturer’s recommendations. For microarray analysis, RNA was matched healthy controls were recruited by advertisement. Lupus disease further purified and concentrated using an RNeasy micro kit and following activity was assessed by the SLE disease activity index (42) (Supplemental the manufacturer’s recommendations (Qiagen, Valencia, CA). RNA sam- Table I). ples were processed on an Agilent 2100 BioAnalyzer (Agilent Technolo- gies, Santa Clara, CA) to assess RNA integrity. Cell isolation and culture and fluorescent microscopy Microarray data processing, analysis, and pathway mapping Human PBMCs, known to contain both EPCs and CACs (43–45), were Affymetrix Human U133 Plus 2.0 Genechips (Affymetrix, Santa Clara, CA) isolated and cultured under proangiogenic stimulation, as previously de- by guest on September 29, 2021 scribed (11), with a few modifications. Briefly, PBMCs (2.27 3 106/cm2) were processed at the University of Michigan Microarray Core Facility following the manufacturer’s instructions (46). The samples analyzed and were cultured in endothelial cell-specific enrichment medium (EBM2; a Cambrex, East Rutherford, NJ) on fibronectin-coated wells (BD Bio- compared were as follows: untreated and IFN- –treated peripheral blood EPCs/CACs from healthy control and lupus patients (n = 6 in each group), sciences, Franklin Lakes, NJ). Typically, after 1–3 wk in culture, these cells a differentiate into mature endothelial cells that display typical mature as well as untreated and IFN- –treated bone marrow EPCs from healthy n endothelial cell markers and display functional characteristics of vascular controls ( = 5 in each group). The CEL files were normalized in Gene- cells (11, 43–45). For some of the experiments (gene expression studies), Pattern pipeline (http://www.GenePattern.org) using the RMA (Robust media was changed after 72 h and fresh media was added with or without MultiChip Average) method and the Human Entrez Gene custom CDF an- human rIFN-a 2b (Schering-Plough, Kenilworth, NJ) at a final concentra- notation version 10 (http://brainarray.mbni.med.umich.edu/Brainarray/de- tion of 1000 IU/ml. Cells were incubated in the presence or absence of IFN- fault.asp). Of the 17,527 gene IDs (corresponding to the 54,675 Affymetrix a for 6 h prior to RNA harvesting. This dose was chosen due to its effects in probesets), the number of genes expressed above the Poly-A Affymetrix inhibiting vasculogenesis in control EPC/CAC cultures (11). Similar ex- control expression baseline (negative controls) and used for further analyses periments were performed with EPCs directly obtained from control bone were, respectively, 15,700, 15,186, and 15,909 in the healthy control + n n marrow. In brief, CD133 cells obtained from healthy control bone marrows peripheral blood cells ( = 12), the SLE peripheral blood cells ( = 12), and n (AllCells, Emeryville, CA) were thawed following manufacturer’s recom- the healthy bone marrow EPCs ( = 10). Normalized data files are available mendations, and next cultured in StemSpan SFEM (StemCell Technologies, on Gene Omnibus Web site, under the reference number GSE23203 (http:// Vancouver, British Columbia, Canada) for 48 h to allow for cell recovery www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23203). Statistical paired analyses were performed using significance analysis of microarrays com- and expansion, then under similar conditions as peripheral blood EPCs/ a 3 5 paring control IFN- –treated with untreated peripheral blood cells, lupus CACs, but at a density of 5 10 cells/ml. a a To assess the capacity of peripheral blood EPCs/CACs to differentiate IFN- –treated with untreated peripheral blood cells, and healthy IFN- – into mature endothelial cells, media was changed 120 h after plating, then treated with untreated bone marrow EPCs. The significantly regulated genes q , every 3 d. On days 14–21, cells were incubated with markers of mature en- between the groups ( 0.05 depicting the false discovery rate) were ana- dothelial cells, including 19-dioctadecyl-3,3,39,39-tetramethylindocarbocya- lyzed by building biological literature-based networks using Genomatix nine perchlorate–acetylated low-density lipoprotein (LDL; Biomedical Bibliosphere Pathway Edition software (Genomatix, Munich, Germany; Technologies, Stoughton, MA), and FITC Ulex europaeus agglutinin-1 http://www.genomatix.de) (47, 48). Canonical pathways were analyzed us- (UEA-1; Vector Laboratories, Burlingame, CA). In experiments to assess the ing the Ingenuity Pathway Analysis Software (http://www.ingenuity.com). effect of exogenous proangiogenic molecule effects on SLE and control EPC/ Real-time quantitative PCR CAC function, IL-1b (10 ng/ml), IL-6 (10 ng/ml), TNF-a (10 ng/ml; PeproTech, Rocky Hill, NJ), or vascular endothelial growth factor (VEGF; Total RNAwas transcribed into cDNA using oligo(dT) and Moloney murine 1 mg/ml; National Cancer Institute, Bethesda, MD) was added to EPC/CAC leukemia virus (Invitrogen, Carlsbad, CA) with 1 mg RNA using a My- cultures and replenished every 48 h. Cycler thermocyler (Bio-Rad, Hercules, CA), and levels of expression of To assess endothelial cell morphology and expression of endothelial cell the following genes were measured: IL-1b,59-ATG TCT GGA ACT TTG markers, cells were analyzed by fluorescent microscopy using a Leica GCC ATC TT-39 (forward) and 59-AGA CAA TTA CAA AAG GCG AAG (Bannockburn, IL) DMIRB fluorescent inverted microscope. Images were AAG ACT-39 (reverse); IL-1a,59-CCA GAA GAA GAG GAG GTT GGT acquired at room temperature using live cells in PBS without mounting C-39 (forward) and 59-CTG CCC AAG ATG AAG ACC AAC CA-39 (re- media. A total of eight random fields of view was acquired, and images were verse); IL-1RN,59-CCT CAG ATA GAA GGT CTT CTG GTT AAC-39 analyzed using the CellC program (http://www.cs.tut.fi/sgn/csb/cellc/) to (forward) and 59-ATG CTG ACT CAA AGG AGA CGA TC-39 (reverse); The Journal of Immunology 4459

IL-1R1,59-GAA GCC TGA TGT TTC TCT GAC TAA AAT GA-39 (for- studied groups; a q value ,0.05 was considered significant. For all other ward) and 59-AGG TCT TGG AAA AAC AGT GTG GATATA AG-39 (re- studies, a paired Student’s t test or, in the case of the ELISA analysis, verse); IL-1R2,59-AAA ATT TGC GGG TAT GAG ATG AAC G-39 a Mann-Whitney t test was performed to determine differences; a p value (forward) and 59-ACG TCT GCA CTA CTA GAA ATG CTT C-39 (reverse); ,0.05 was considered significant. VEGF-A,59-GGT CTC GAT TGG ATG GCA GTA G-39 (forward) and 59- CAC CCA TGG CAG AAG GAG GA-39 (reverse); MX-1,59-TACCAG- GACTACGAGATTG-39 (forward) and 59-TGCCAGGAAGGTCTATTAG- Results 39 (reverse); and b-actin,59-CAT CAC GAT GCC AGT GGT ACG-39 IFN-a induces an antiangiogenic signature in control and (forward) and 59-AAC CGC GAG AAG ATG ACC CAG-39 (reverse). lupus EPCs/CACs Real-time PCR was carried out using an ABI PRISM 7900HT (Applied Biosystems, Foster City, CA) with the following cycling conditions: an The demographic and clinical characteristics of the patients and initial denaturing/activation at 95˚C for 10 min, followed by 40 cycles of controls studied are included in Supplemental Table I. The effect of denaturing at 95˚C for 30 s, annealing at 52˚C for 30 s, and elongation at IFN-a on peripheral blood EPCs/CACs and on bone marrow 72˚C for 30 s. EPCs exposed to proangiogenic stimulation on steady state mRNA Assessment of serum protein levels, EPC/CAC proliferation, levels was assessed with Affymetrix genechip microarrays. IFN- and apoptosis a–treated versus untreated control and lupus cells exposed to angiogenic stimulation showed no differential expression in IFN-a Serum IL-1R antagonist (IL-1RN) and IL-1b were quantified by ELISA (R&D Systems), following the manufacturer’s instructions. EPC/CAC mRNA, but did show a significant up-regulation of type I IFN- proliferation and caspase 3/7 activation were assessed after 1 d in proan- inducible genes (Table I). giogenic culture using the XTT cell proliferation kit (Cayman Chemical, For the healthy control EPCs/CACs, a total of 2850 genes (q

Ann Arbor, MI) and the Apo-ONE caspase 3/7 assay (Promega, Madison, ,0.01) was found to be differentially regulated by IFN-a (Sup- Downloaded from WI), respectively, following the manufacturers’ instructions. plemental Table III). Assessing the association of these transcripts Assessment of myeloid cell phenotype with canonical pathways using ingenuity pathway analysis identiﬁed a After 5 d in proangiogenic culture in the presence or absence of 10 ng/ml IFN signaling as the top regulated pathway in IFN- –treated cells IL-1b, cells were harvested using cell dissociation buffer (Invitrogen) and compared with nontreated (p = 3.98E-05; Supplemental Table IV). incubated with the following ﬂuorochrome-conjugated anti-human mAbs: Transcriptional network analysis integrating differentially regulated

anti-CD14, anti-CD11c, anti-class II MHC (Ancell, Bayport, MN), and mRNAs with literature mining and automated promoter analysis http://www.jimmunol.org/ anti-CD86 (BD Biosciences). Immunofluorescence was quantified by (Bibliosphere software suite; Genomatix) highlighted IL-1b and FACS with a FACSCalibur, followed by analysis with FlowJo. VEGF-A among important regulatory nodes (Supplemental Fig. 1). Human kidney tissue and immunohistochemistry IL-1b and VEGF-A were significantly downregulated in IFN-a– Kidney tissue was obtained from 25 renal biopsies from subjects with treated control EPCs/CACs when compared with untreated cells clinical and histological diagnosis of lupus nephritis [5 with class II, 5 with (0.7-fold for both genes, q , 0.05; Table I). class III, 5 with class IV, and 5 with class V, according to the new SLE Based on these results, we verified whether IL-1b was also nephritis classification (49)]; anti-neutrophil cytoplasmic Ab (ANCA)- regulated in lupus EPCs/CACs after IFN-a exposure. Affymetrix associated vasculitis (n = 5); and, for comparison, normal samples from 5 control kidneys from tumor nephrectomies. Relevant clinicohistological microarray analysis defined 1631 genes significantly up- and down- parameters are given in Supplemental Table II. regulated by exogenous IFN-a, with a fold-change $0.15 between by guest on September 29, 2021 Tissue samples for light microscopy were fixed in 4% buffered para- the untreated and treated lupus cells (q , 0.05; Supplemental Table formaldehyde and embedded in paraffin. Routine stainings were performed V). IFN signaling also appeared as the top regulated pathway according to standard techniques. (p = 5.75E-07; Supplemental Table V). Similar to the IFN-a– For immunoperoxidase staining, sections were rehydrated, then im- mersed in 10 mM citrate buffer (pH 6.0), treated with microwave irradiation treated control cells, the literature-based network analysis of those at 500 W for 10 min, and cooled at room temperature. After incubation genes highlighted a major IL-1b node. This IL-1b node and the with 0.5% avidin (Sigma-Aldrich, Gallarate, Milan, Italy) and 0.01% biotin regulated gene nodes with a direct edge to IL-1b (201 genes in total) (Sigma-Aldrich), to suppress endogenous avidin-binding activity, 3% H2O2 are displayed in Fig. 1 and listed in Supplemental Table VI. IL-1b solution was applied to block endogenous peroxidase. After washing, sec- a tions were sequentially incubated with the primary Abs CD31, IL-1b, was downregulated 0.6-fold in IFN- –treated SLE cells when and IL-1RN (Abcam, Cambridge, U. K.), then with the secondary bio- compared with untreated SLE cells (Table I). IL-1RN is a member tinylated Ab (Zymed Laboratories, HistoLine, Milan, Italy) and with of the IL-1 family that binds to IL-1Rs without inducing a cellular peroxidase-labeled streptavidin (Zymed Laboratories). Peroxidase activity response, thereby antagonizing the effects of IL-1a and IL-1b (50, was detected with 3,5-diaminobenzidine (Sigma-Aldrich), and sections 51). IL-1RN mRNA expression was upregulated 11-fold in SLE were dehydrated and mounted in Bio Mount (Bio Optica, Milano, Italy). a a Specificity of Ab labeling was demonstrated by the lack of staining after cells after treatment with IFN- , whereas IL-1 was downregu- substituting PBS and proper control Igs (Zymed Laboratories) for the lated (0.43-fold) in the IFN-treated cells (Table I; q , 0.05). The primary Ab. expression of IL-1RN gene was doubled in SLE compared with the Images were acquired by a Zeiss Axioscope 40FL microscope, equipped healthy control EPCs/CACs (fold-change 11.0 versus fold-change with AxioCam MRc5 digital video camera (Carl Zeiss SpA, Arese, Italy). Images were recorded using AxioVision software 4.3 and analyzed by the 4.2, respectively; Table I). Similar to what was found in the control AxioVision analysis module (Carl Zeiss SpA). A color threshold procedure cells, treatment with IFN-a led to decreased expression of the allowed selective highlighting of the stained areas in gray mode, and the proangiogenic molecule VEGF-A (52) (fold-change 0.78) in the software was programmed to calculate automatically the percentage of the lupus cells (Table I). Thus, microarray analysis of EPCs/CACs area or the number of particles occupied by staining. from control and SLE patients exposed to proangiogenic stimuli Renal biopsies were included in the study if a number of 9 or more glomeruli were present. For quantitative evaluation, all glomeruli and medium/ identified an antiangiogenic signature secondary to type I IFN large vessels in human biopsies and 20 glomeruli and 5 medium/large vessels treatment and a more pronounced antiangiogenic response in SLE incontrolkidneyswereconsidered.Asforthetubulointerstitialcompartment, than in control cells in response to this cytokine. consecutive images were taken at original magnification 3200 avoiding Healthy CD133+ bone marrow EPCs were found to have 710 glomeruli. The whole specimen was scanned in renal biopsies, and 20 fields , a were sampled in control kidneys. genes (q 0.05; Supplemental Table VII) regulated by IFN- . Again the IFN signaling pathway was identified as the top regu- Statistical analysis lated one (p = 6.76E-10, ingenuity pathway analysis; Supplemen- For Affymetrix microarray studies, the significance microarray analysis tal Table VII). Although the IFN-a and b mRNA expression were was used to define genes significantly differentially regulated between the not modified, the IFN-inducible genes showed significant upreg- 4460 EFFECTS OF IFN-a ON VASCULOGENESIS IN LUPUS

Table I. Affymetrix microarray expression data of studied genes in peripheral blood EPCs/CACs and bone marrow EPCs

IFN-a–Treated IFN-a–Treated IFN-a–Treated Compared with Compared with Compared with Nontreated Healthy Nontreated SLE Nontreated Healthy Control Peripheral Blood Peripheral Blood EPCs/ Control Bone Marrow EPCs/CACs CACs EPCs

Entrez Gene ID Gene Symbol Gene Name Fold-Change q Value Fold-Change q Value Fold-Change q Value IFN genes 3439 IFN-a1 IFN-a1 1.29 0.243 1.08 0.242 1.06 0.999 3440 IFN-a2 IFN-a2 N/A N/A N/A N/A N/A N/A 3454 IFNAR1 IFN (a, b, and v) 0.79 0.005* 0.79 0.002* 0.80 0.144 receptor 1 3455 IFNAR2 IFN (a, b, and v) 1.05 0.471 1.12 0.079 0.93 0.506 receptor 2 IFN-inducible genes 4599 MX1 Myxovirus resistance 1, 2.74 0.000* 6.00 0.000* 6.09 0.003* IFN-inducible protein p78 10561 IFI44 IFN-induced protein 44 1.57 0.000* 3.42 0.000* 2.35 0.021* 10964 IFI44L IFN-induced protein 44-like 1.56 0.001* 9.92 0.000* 3.75 0.020* 3434 IFIT1 IFN-induced protein with 2.16 0.000* 8.44 0.000* 9.84 0.000* tetratricopeptide repeats 1 Downloaded from IL-1 and receptors 3552 IL-1a IL-1, a 0.50 0.003* 0.43 0.001* 0.64 0.214 3553 IL-1b IL-1, b 0.70 0.009* 0.62 0.001* 0.84 0.162 3557 IL-1RN IL-1RN 4.18 0.000* 10.98 0.000* 3.37 0.024* 3554 IL-1R1 IL-1R, type 1 0.66 0.003* 0.76 0.007* 0.86 0.414 7850 IL-1R2 IL-1R, type 2 1.63 0.002* 1.48 0.008* 1.27 0.386

3556 IL-1RAP IL-1R accessory protein 0.75 0.009* 1.05 0.211 0.98 0.999 http://www.jimmunol.org/ Markers of apoptosis 836 CASP3 Caspase 3 1.43 0.002* 0.95 0.000* 1.16 0.084 840 CASP7 Caspase 7 1.30 0.001* 2.56 0.000* 1.58 0.012* Other genes 7422 VEGFA VEGF-A 0.66 0.002* 0.78 0.002* 1.04 0.999 5175 PECAM1 Platelet/endothelial cell 1.10 0.091 1.05 0.242 0.88 0.098 adhesion molecule pq , 0.05 was considered significant. N/A, not expressed above the Affymetrix control baseline. by guest on September 29, 2021 ulation in IFN-a–treated compared with untreated bone marrow addition of IL-1b and/or VEGF-A to lupus EPC/CAC cultures cells (fold-changes from 2.35 to 9.84; Table I). As observed in the would restore the capacity of these cells to differentiate into a healthy control and lupus PBMCs, IL-1RN mRNA was 3.4-fold mature endothelium. To this end, rIL-1b and/or VEGF-A were increased when cells were exposed to IFN-a compared with non- added to proangiogenic media, and the number of mature endo- exposed cells. thelial cells was counted as determined by the uptake of acetylated Analysis by real-time PCR confirmed that IL-1b, IL-1R1, and LDL and the binding of the UEA-1 lectin in control and SLE cells VEGF-A mRNA levels were significantly downregulated and IL- after 14–21 d in culture. We again confirmed a significant decrease 1RN and the decoy receptor IL-1R2 significantly upregulated in IFN- in the capacity of SLE EPCs/CACs to differentiate to mature en- a–treated control and lupus peripheral blood EPCs/CACs when dothelial cells when compared with control samples. Addition of compared with untreated cells (p , 0.05; Fig. 2A). Because higher IL-1b significantly increased the number of mature endothelial levels and/or increased sensitivity to type I IFNs have been previously cells by 3-fold in lupus cell cultures when compared with media reported in SLE (53, 54), we then assessed whether similar changes in alone (p = 0.010; Fig. 3A,3B). VEGF-A also increased the number IL-1–related molecules were seen at the protein level in vivo. A sig- of mature endothelial cells by 2-fold (p = 0.045; Fig. 3A,3B). The nificant increase in circulating IL-1RN levels could be detected in specificity of the response to molecules regulated by IFN-a was the serum of SLE patients compared with healthy controls (p , 0.02; demonstrated, as treatment with other proangiogenic factors (IL-6 Fig. 2B). Both circulating IL-1b and IL-1a protein levels were below and TNF) (55–57) not regulated by IFN-a treatment in the gene the limit of detection in SLE and control serum (data not shown). We expression analysis (data not shown) did not result in any im- had previously reported that SLE patients have decreased serum provement in EPC/CAC function (Fig. 3A,3B). In addition, the levels of VEGF-A compared with healthy controls, further supporting beneficial effect of IL-1 and VEGF-A was only seen in SLE sam- the microarray and real-time PCR data (11). ples, but not in controls (Fig. 3A,3B). IL-1b restores the capacity of lupus EPCs/CACS to IL-1b abrogates the defects in proliferation and viability of differentiate into mature endothelial cells lupus EPCs/CACs We had previously reported that lupus EPCs/CACs, in contrast to Various mechanisms may lead to improvements in lupus EPC/CAC control cells, fail to effectively differentiate into endothelial-like function by addition of IL-1b, including increased proliferation or cells. Lupus EPCs/CACs cannot form a mature endothelial mono- increased viability, including modulation of caspase activity. IL- layer when cultured under proangiogenic stimulation on fibronectin- 1b has been shown to increase proliferation of murine EPCs (58), coated wells. We previously showed that IFN-a blockade restores rat bone marrow cells (59), and human T (60–62) and B cells (61, the functional capacity of lupus EPCs/CACs (11). Given that IFN-a 63). IL-1b is also able to inhibit apoptosis and promote survival of downmodulated IL-1 and VEGF pathways, we next tested whether monocytes (64) and granulocytes (65). With evidence for increased The Journal of Immunology 4461 Downloaded from http://www.jimmunol.org/ by guest on September 29, 2021

FIGURE 1. Transcriptional network displaying IL-1b as a major node regulated by IFN-a on EPCs/CACs. Literature-based Genomatix Bibliosphere network was performed. The network generated from the regulated gene list between nontreated and IFN-a–treated SLE PBMCs displayed IL-1b as one of the main nodes (1631 genes with a fold-change $0.15 and a q value ,0.05; n = 6 in each group). The 1208 genes passed the Bibliosphere filter criterion, based on the cocitation of genes in PubMed abstract sentence linked by a function word (B2 filter). Only the 201 IL-1b directly connected regulated genes are displayed. The color code from red to blue indicates from up- to downregulation of genes in IFN-a–treated SLE PBMCs compared with nontreated SLE PBMCs. proliferation and viability possibly playing a role in the improve- pases were significantly upregulated by IFN-a treatment (Table I), ment in EPC/CAC function, we tested whether supplementation and caspase 3 was also a subnode in the literature-based Biblio- with IL-1b and/or VEGF-A promoted increases in proliferation sphere network (Fig. 1). Untreated lupus EPCs/CACs displayed and/or protection from apoptosis. SLE and control cells were cul- significant increases in caspase 3/7 activation in the presence of tured with proangiogenic media in the presence or absence of IL- media alone, when compared with control cells (Fig. 4B), indi- 1b and/or VEGF-A for 24 h. Lupus EPC/CAC proliferation was cating increased apoptosis. Treatment of lupus EPC/CAC cultures significantly increased by the addition of rIL-1b (p = 0.023) or with rIL-1b significantly inhibited caspase 3/7 activation (p = 0.045; VEGF-A (p = 0.019) when compared with cells cultured with Fig. 4B), whereas treatment with VEGF-A did not have any effect. A media alone (Fig. 4A). Treatment with a combination of IL-1b and combination of rIL-1b and VEGF-A decreased caspase 3/7 activity VEGF-A did not show a synergistic or additive effect on prolif- to a similar level as IL-1b treatment alone. These results indicate eration compared with cells treated with IL-1b or VEGF-A only that both IL-1b and VEGF-A can improve EPC/CAC proliferation, (Fig. 4A). When control EPCs/CACs were treated with IL-1b, there but only IL-1b has an effect in inhibiting enhanced apoptosis on was a trend of increased proliferation (p = 0.084). Control cells these cells. In contrast, neither IL-1b nor VEGF-A addition had any treated with VEGF-A alone did not show any improvement in effect on healthy control EPC/CAC apoptosis (Fig. 4B). proliferation, but the combination of IL-1b and VEGF-A did sig- b nificantly (p = 0.016) improve proliferative capacity (Fig. 4A). IL-1- decreases lupus DC differentiation Caspases 3 and 7 play a central role in the execution phase We previously reported that, in EPC/CAC cultures, IFN-a alters of apoptosis (66), and activation of these molecules is used as a the expression of surface developmental markers on myelomo- marker of programmed cell death. The mRNA levels of these cas- nocytic cells, consistent with skewing the differentiation of these 4462 EFFECTS OF IFN-a ON VASCULOGENESIS IN LUPUS

FIGURE 2. IL-1 family members and VEGF-A are regulated by IFN-a in lupus and control EPCs/CACs. A, Regulation of IL-1b, IL-1R1, IL-1R2, IL- 1RN, and VEGF-A mRNA levels by IFN-a was confirmed by real-time PCR in EPCs/CACs from healthy controls and SLE patients. Results represent the mean 6 SEM log fold-change of IFN-a–treated over untreated cells. All treated samples were significantly altered with a p , 0.05 when compared with untreated samples (SLE, n = 11; control n = 17). B, SLE patients display elevated levels of IL-1RN in plasma (p = 0.0116). Results represent mean 6 SEM plasma levels of IL-1RN in 35 SLE patients and 10 healthy controls. cells from angiogenic CACs to IFN-a–derived DCs. Indeed, IFN-a absence of IL-1b. Addition of IL-1b led to a significant down- induces a significant reduction in DC-dendritic cell-specific in- regulation of the mature DC markers CD86 and MHC class II on tercellular adhesion molecule-3–grabbing nonintegrin (SIGN)+ SLE patients, and a similar trend was observed in healthy controls Downloaded from CD14+ cells, CD86 upregulation, and overall downregulation of (Table II). There was also a decrease in CD11c+ CD142 cell CD14 (11). To address whether addition of IL-1b could inhibit population, indicating a decrease in total DCs. Additionally, ex- this phenomenon and allow myeloid lupus cells to favor proan- pression of CD14 was increased in cultures, suggesting an in- giogenic differentiation rather than DC differentiation, surface crease in myeloid CACs. These results indicate that the skewing of markers of mature DCs were examined in 5-d cultures of lupus myeloid cells into nonangiogenic pathways by IFN-a is mediated, PBMCs subjected to proangiogenic stimulation in the presence or at least in part, by downregulation of IL-1 pathways. http://www.jimmunol.org/ by guest on September 29, 2021

FIGURE 3. IL-1b abrogates the abnormal phenotype of lupus EPCs/CACs. A, Addition of rIL-1b to lupus EPC/CAC cultures improves the ability of these cells to differentiate into mature endothelial cells to levels comparable to those of healthy controls (ppp , 0.01; n = 24), whereas addition of rVEGF-A resulted in a more modest, but significant improvement (pp , 0.05; n = 24). Addition of IL-6 or TNF-a to the same cultures had no beneficial effect when compared with untreated cultures (n = 9). Control cells showed no significant improvement in their capacity to differentiate into mature endothelial cells with any of the treatments mentioned above (n =7,n =5,n = 3, and n = 3, respectively). Results are expressed as a ratio of the number of endothelial cells/high power field to the number of untreated lupus endothelial cells/high power field (pp , 0.05). B, Representative images displaying the effects of these proteins on EPC/CAC cultures from two SLE patients at 2–3 wk. Original magnification 3100; scale bar, 200 mm. Mature endothelial cells show coexpression of FITC UEA-1 (green) and uptake of 19-dioctadecyl-3,3,39,39-tetramethylindocarbocyanine perchlorate-acetylated LDL (red). The Journal of Immunology 4463

a role in VEGF-A changes observed secondary to IFN-a, we analyzed mRNA expression of known HuR targets (69) in the microarray expression profiles. Of the 14 HuR targets examined, only 4 (including VEGF-A mRNA) were significantly reduced in lupus EPCs/CACs treated with IFN-a, whereas 3 were reduced in the IFN-treated control EPCs/CACs (Table III). Whereas HuR mRNA was significantly reduced in both control and SLE EPCs/CACs upon exposure to IFN-a, several HuR targets were either upregulated or unchanged after IFN-a treatment. Overall, these results suggest that HuR-dependent RNA degradation is unlikely to be an important mechanism for VEGF-A reduction induced by IFN-a. Furthermore, control bone marrow CD133+ EPCs did not show any significant HIF1A or HuR mRNA expression changes in response to IFN-a (Table III). The large family of IFN-ab proteins all bind to a single type of receptor, which is composed of two chains: IFNAR1 and IFNAR2. The intracellular domain of IFNAR1 associates with a member of the JAK kinase family, Tyk2, whereas IFNAR2 associates with FIGURE 4. IL-1b increases proliferation and inhibits apoptosis of lupus Jak1. The major substrates for tyrosine phosphorylation subsequent Downloaded from EPCs/CACs. A, Improvements in EPC/CAC proliferation by IL-1 and to IFNR binding are members of the STAT family of transcription VEGF-A supplementation. Results represent mean 6 SEM absorbance in factors. These proteins are normally latent and reside in the cyto- duplicate wells. pp , 0.05 (SLE, n = 5; controls, n = 8). B, IL-1b inhibits plasm in unstimulated cells. Once phosphorylated, STAT1 and activation of caspases 3 and 7 in lupus, but not control EPCs/CACs. Results STAT2 dimerize and assemble with IFN regulatory factor-9 to form represent mean fluorescent value of treated samples/mean fluorescent value the multimeric transcription factor, latent cytosolic transcription of SLE media alone 6 SEM. SLE, n = 5; control, n =8;pp , 0.05. factor. Latent cytosolic transcription factor binds to the IFN- http://www.jimmunol.org/ stimulated response element of IFN-stimulated genes in the nu- cleus and activates their transcription (70). From the microarray a IFN- regulates IL-1 pathways in EPCs/CACs through analyses, the JAK/STAT pathway was one of the most significantly JAK-STAT modulation regulated canonical pathways in control and SLE EPCs/CACs after Various pathways potentially involved in the regulation of IL-1 IFN-a treatment (p = 0.023 and 0.017, respectively). Indeed, SLE family members and VEGF were investigated. Hypoxia-inducible peripheral blood EPCs/CACs exposed to IFN-a significantly up- factor (HIF)-1a is the main regulator of VEGF-A expression, regulated STAT1, 2, 3, 4, 5A, and 6, whereas control EPCs/CACs mainly by posttranslational regulation via proteasomal degrada- significantly upregulated STAT2, 4, 5A, and 6 (Table III) and con- tion and stabilization by von Hippel-Lindau factor (67). HIF-1a is a trol bone marrow CD133+ EPCs significantly upregulated STAT1 by guest on September 29, 2021 transcription factor, and 117 genes, including IL-1b and VEGF-A, and 2 in response to IFN-a treatment (Table III). Confirming the of the 2850 in SLE EPCs/CACs, have an ischemia response ele- array data, when control and SLE peripheral blood EPCs/CACs ment contained in their promoter. A significant decrease of HIF- allowed to differentiate for 3 d were stimulated with IFN-a for 1a mRNA expression was detected in lupus EPCs/CACs treated 30 min, there were significant increases in phosphorylation of both with IFN-a; the significance was not reached in control cells (Table STAT2 and 6 (p , 0.05; Fig. 5). We then performed subanalysis on III). However, there was no significant correlation between mRNA EPCs and CACs; in the EPCs, STAT2 and 6 were significantly levels of HIF-1a and VEGF-A in each group studied (data not activated upon IFN-a stimulation (p = 0.04 and 0.02, respectively; shown), indicating that it is unlikely that the changes in HIF-1a Fig. 5A), whereas in CACs there was a significant activation of steady state mRNA levels induced by IFN-a were the main deter- STAT2 (p , 0.05; Fig. 5B) and a trend toward STAT6 activation. minants of VEGF-A downregulation in EPCs/CACs. We then tested whether JAK inhibition would abrogate the down- Regulation of VEGF-A occurs not only at the transcriptional regulation of proangiogenic molecules seen in IFN-a–treated cells. level, but also postranscriptionally (68), and includes mRNA sta- Indeed, the pan-JAK inhibitor pyridone 6 induced significant up- bilization by the Hu Ag R (HuR; or embryonic lethal, abnormal regulation of IL-1a, IL-1b, IL-1R1, and VEGF-A (p = 0.02, 0.001, vision [ELAV]), a ubiquitously expressed RNA-binding protein 0.01, and 0.01, respectively; Fig. 5C) and downregulation of IL- (68). To determine whether HuR mRNA stabilization may play 1RN and the canonical type I IFN-inducible gene MX1 (p = 0.06

Table II. Effect of IL-1b on myelomonocytic cell differentiation

Healthy controls Lupus

Untreated +IL-1b p Value Untreated +IL-1b p Value CD14 61.4 6 6.23 75.9 6 6.63 0.018 51.7 6 6.82 75.3 6 4.68 0.002 CD11c 51.8 6 4.70 50.3 6 6.56 0.779 46.6 6 6.64 41.7 6 7.61 0.492 DC-SIGN 21.7 6 6.98 12.2 6 1.87 0.318 20.9 6 6.68 5.8 6 1.82 0.033 CD86 57.5 6 3.29 36.1 6 7.21 0.117 40.5 6 5.93 28.4 6 5.62 0.079 MHC class II 55.2 6 12.25 35.7 6 16.28 0.037 22.0 6 4.75 7.7 6 3.16 0.001 CD11c+CD86+ 44.8 6 4.16 19.9 6 1.72 0.011 32.1 6 4.93 14.1 6 3.52 0.006 CD14+DC2 SIGN+ 20.3 6 6.65 11.1 6 0.81 0.282 18.8 6 7.22 5.7 6 1.98 0.065 CD11c+CD142 1.03 6 0.31 0.18 6 0.11 0.024 1.8 6 0.46 0.6 6 0.28 0.002 Numbers indicate mean percentage of positive cells 6 SEM. p , 0.05 is considered signiﬁcant. 4464 EFFECTS OF IFN-a ON VASCULOGENESIS IN LUPUS

Table III. Affymetrix microarray expression data of STAT, HIF1A, HuR, and HuR target genes in peripheral blood EPCs/CACs and bone marrow EPCs

Entrez Gene ID Gene Symbol Gene Name Fold-Change q Value Fold-Change q Value Fold-Change q Value STAT genes 6772 STAT1 STAT1 1.06 0.198 1.45 0.031* 2.61 0.000* 6773 STAT2 STAT2 1.43 0.000* 1.69 0.000* 1.86 0.000* 6774 STAT3 STAT3 1.02 0.480 1.54 0.001* 1.45 0.123 6775 STAT4 STAT4 1.10 0.025* 1.49 0.036* 1.23 0.445 6776 STAT5A STAT5A 1.25 0.001* 1.21 0.003* 1.04 0.619 6777 STAT5B STAT5B 0.97 0.329 1.04 0.217 1.01 0.999 6778 STAT6 STAT6 1.19 0.014* 1.22 0.000* 1.06 0.623 HIF1-a, HuR, and HuR target genes 3091 HIF1A HIF1A 0.96 0.243 0.96 0.036* 0.94 0.456 1994 ELAVL1 ELAV (Drosophila)-like 1, 0.88 0.026* 0.85 0.002* 0.84 0.070 Hu Ag R 153 ADRB1 Adrenergic b-1R 1.08 0.347 1.05 0.228 1.08 0.627 8900 CCNA1 Cyclin A1 4.50 0.000* 8.32 0.000* 6.12 0.000* Downloaded from 891 CCNB1 Cyclin B1 0.91 0.076 0.89 0.041* 0.90 0.150 595 CCND1 Cyclin D1 0.67 0.001* 1.46 0.012* 1.04 0.999 2353 FOS FBJ murine osteosarcoma 0.74 0.009* 0.67 0.006* 1.16 0.627 viral oncogene homolog 4609 MYC V-myc myelocystoma-tosis 0.86 0.102 1.07 0.999 0.88 0.999 viral oncogene homolog

3562 IL-3 IL-3 0.91 0.295 0.79 0.999 1.03 0.999 http://www.jimmunol.org/ 4613 MYCN V-myc myelocystoma-tosis 1.03 0.451 1.06 0.201 1.01 0.999 viral-related oncogene, neuroblastoma derived 4763 NF1 Neurofibromin 1 1.05 0.368 0.86 0.016* 1.23 0.480 1026 CDKN1A Cyclin-dependent kinase 1.002 0.502 1.27 0.002* 1.07 0.548 inhibitor 1A 5055 SERPINB2 Serpin peptidase inhibitor, 1.07 0.283 1.18 0.193 0.78 0.232 clade B, member 2 7124 TNF TNF 1.03 0.476 1.49 0.001* 1.09 0.651 7422 VEGFA VEGF-A 0.66 0.002* 0.78 0.002* 1.04 0.999 2596 GAP43 Growth-associated protein 43 N/A N/A 1.03 0.211 0.97 0.548 by guest on September 29, 2021 pq , 0.05 was considered significant. N/A, not expressed above the Affymetrix control baseline. and 0.05, respectively; Fig. 5D) in both IFN-a–treated control and patients with lupus nephritis had a significant decrease in VEGF-A lupus EPCs/CACs. In contrast, there was no change in level of expression when compared with control biopsies or biopsies from expression of IL-1R2 mRNA after JAK inhibition. patients with vasculitis and similar degree of kidney function. This The PI3K pathway is also activated by IFN-a in various cell was observed in class II–V lupus nephritis, but was most pro- types, and PI3K interacts with the JAK-STAT signaling pathway nounced in classes IV and V (Fig. 6). Confirming the in vitro data and aids in the activation of a limited number of genes (71). To on IFN-treated EPCs/CACs and the serum findings in SLE, IL- assess whether PI3K pathway was also involved in the induction of 1RN was detected in the renal blood vessels of patients with lupus an antiangiogenic signature in IFN-treated EPCs/CACs, we per- nephritis (particularly class V), but not in the blood vessels of formed similar experiments using a PI3K inhibitor. In contrast to control patients or patients with ANCA-positive vasculitis. IL-1b what was observed with a JAK inhibitor, PI3K inhibition did not was not detected by immunohistochemistry in any of the tissues induce significant changes in any of the genes examined. Overall, examined. The density of the peritubular and interstitial vessels these results indicate that the antiangiogenic signature induced by was evaluated. CD31 expression, used as a marker of endothelial IFN-a on EPCs/CACs is signaled through JAK-STAT pathways. cell density, was significantly decreased in the glomerular compartment of lupus nephritis biopsies (particularly class V) when Decreased endothelial density and altered IL-1 pathways are compared with control biopsies, and the levels of this molecule in observed in SLE in vivo the renal blood vessels were significantly decreased in all subsets Whereas our group and others have suggested decreased vascu- of lupus nephritis compared with control or ANCA-positive vas- logenesis in human SLE (11, 14) and murine lupus models also culitis (Fig. 6). These results indicate that decreased vasculo- show similar abnormalities in vivo (23), there was no previous genesis is also occurring in vivo in SLE and that changes in mol- evidence on the occurrence of this phenomenon in vivo in humans. ecules involved in IL-1 signaling and VEGF-A are also observed To this end, we proceeded to examine the glomeruli and renal at the tissue level in this disease. blood vessels of lupus nephritis biopsies and compared blood vessel density and protein expression of IL-1RN and VEGF-A in Discussion these compartments with those of control kidneys as well as renal Whereas it is widely accepted that SLE patients exhibit greater biopsies from patients with another immune-mediated disease, propensity to develop CV complications (5, 72), the mechanisms ANCA-positive vasculitis (Supplemental Table II). Immunohisto- leading to this enhanced risk remain unclear. Our group and others chemistry analysis revealed that the glomerular compartment of have proposed that IFN-a may play a prominent role in vascular The Journal of Immunology 4465 Downloaded from

FIGURE 5. IFN-a activates STAT2 and 6 on EPCs/CACs, and JAK inhibition leads to downregulation of the antiangiogenic signature in SLE. Phos- phorylation of STAT2 and STAT6 was detected by FACS in EPCs and CACs. Stimulation with IFN-a leads to STAT2 and 6 activation in EPCs (A) and STAT2 activation in CACs. B, Results represent mean percentage + SEM of cells positive for STAT phosphorylation in seven SLE and four control subjects. C, JAK inhibition induces upregulation of IL-1a, IL-1b, IL-1R1, and VEGF-A mRNA and decreases mRNA levels of IL-1RN and MX1 (D). Results represent average fold-change 6 SEM over vehicle-treated cells. SLE, n = 10; control, n =5;pp , 0.05. http://www.jimmunol.org/ damage in SLE, at least in part, by interfering in the balance tion and signaling and downregulation of VEGF-A. Furthermore, between blood vessel damage and repair, leading to a dysfunc- these IFN-induced pathways are operational in vivo in serum and tional endothelium (11, 14). Indeed, abnormalities in vasculogen- tissue of SLE patients. A previous study reported high levels of esis have been proposed to play an important role in the develop- IL-1RN in SLE serum and correlation with lupus disease activ- ment of atherosclerosis and organ damage (including renal failure) ity (81). Lupus PBMCs are also less capable of releasing IL-1b in in various diseases (31, 73–76). response to stimulation (82). However, a link between these ab- Whereas IFN-a is a potent antiangiogenic factor (77–79), the normalities and IFN-a in SLE and their potential role in vascular exact pathways by which this molecule regulates EPC/CAC gene damage in this disease had not been reported. Our results also by guest on September 29, 2021 expression had not been characterized (39, 80). In this study, we support studies performed in other populations, in which exoge- demonstrate that IFN-a exerts its antiangiogenic effects on EPCs/ nous type I IFNs induce IL-1 downregulation and IL-1RN increases CACs through the modulation of molecules relevant to IL-1 func- in patients with viral hepatitis C, as well as previous reports of the

FIGURE 6. Kidneys from patients with lupus nephritis display decreased VEGF-A, increased IL-1RN, and decreased glomerular and capillary density. A and D, Representative photographs show that expression of IL-1RN is negative in the endothelium and vessel wall of a control kidney biopsy. In contrast, the vascular endothelium is clearly stained in a case of class V SLE nephritis, and numerous positive cells are present in the vessel wall, particularly in the external layers. A mild vascular positivity for IL-1RN can be detected in a medium-sized vessel from a case of renal ANCA+ vasculitis (immunoperoxidase, original magnification 3400). B and E, Evident loss of podocyte staining for VEGF-A in glomeruli from class IV lupus nephritis, as compared with control kidneys and ANCA+ vasculitis (immunoperoxidase, original magnification 3200). C and F, Compared with glomeruli from a control kidney and a case of vasculitis, glomerular expression of CD31 is significantly reduced in a case of SLE class III lupus nephritis (immunoperoxidase, original magnification 3400). 4466 EFFECTS OF IFN-a ON VASCULOGENESIS IN LUPUS effect of IFN-a on healthy control myeloid cells in vitro, in which Whereas decreased IL-1 and increased IL-1RN may theoreti- IL-1RN is upregulated without inducing concomitant increases in cally support a phenotype that protects the vasculature, given the IL-1 (83–85). Supporting the hypothesis that other type I IFNs may anti-inflammatory effects, it is reasonable to speculate that in a promote similar modulation, IFN-b also has effects on IL-1 family disease like SLE in which there is ongoing endothelial cell damage members, an indirect effect by inhibiting the ability of T cells to and death (12), a cytokine profile that promotes an antiangiogenic stimulate monocytes to synthesize IL-1b and a direct effect by response would be overall deleterious and could accelerate ath- upregulating IL-1RN synthesis in the latter (86, 87). erosclerosis development. A variety of vascular insults in SLE that Previous studies on hepatocytes report that exposure to type I lead to disease flares (106–108) in conjunction with increased IFNs leads to STAT activation and stimulation of the formation of levels of type I IFNs may lead to periods of endothelial damage, STAT2:STAT6 complexes, subsequently leading to enhanced IL- followed by aberrant repair due to decreased IL-1 and VEGF-A 1RN synthesis (88). In this study, we confirmed that IFN-a led to and increased IL-1RN. This could allow the initiation and ex- STAT2 and 6 phosphorylation in control and lupus EPCs/CACs, pansion of vascular lesions during these flares. and that inhibition of JAK-STAT signaling leads to abrogation of We have also addressed whether these findings are operational the antiangiogenic responses. The effects of JAK inhibition on IL-1 in vivo in SLE, potentially due to increased circulating and/or tissue and VEGF-A mRNA expression are similar to what has been seen IFN-a levels as well as increased sensitivity to this molecule by in other angiogenesis models (89) and in different cell types, includ- SLE cells (53, 109). Kidneys from SLE patients display repression ing macrophages (90). of VEGF-A and induction of IL-1RN, and this correlates with In contrast to the changes observed in peripheral blood EPC/ decreased renal vascular density and vascular rarefaction. These

CAC cultures, bone marrow EPCs responded to IFN-a primarily by results are consistent with our hypothesis of impaired renal vas- Downloaded from significantly upregulating IL-1RN expression, but displayed no sig- culogenesis in SLE and may help to increase our understanding on nificant changes in other IL-1–related molecules or in VEGF-A, the mechanisms leading to loss of renal function in this disease. although a similar trend was observed. These results indicate that Progressive renal disease is characterized by glomerulosclerosis part of the changes seen in peripheral blood were secondary to direct and interstitial fibrosis, and although many studies have focused alterations in the myeloid CAC compartment and/or that EPCs on the mechanisms underlying excessive deposition of extracel-

present in peripheral blood represent a distinct subset responding lular matrix, there is increasing evidence of a vascular component http://www.jimmunol.org/ in different ways to exogenous signals than those EPCs that have as a key driver in the pathogenesis of renal scarring (110, 111). Loss not left the bone marrow. Future studies should investigate this of glomerular and peritubular capillaries is strongly associated with possibility. the progression of chronic kidney disease to end-stage renal disease Whereas IL-1a and IL-1b are considered predominantly proin- in other populations and animal models (112). VEGF-A is consti- flammatory molecules produced in response to infection or cellular tutively expressed in human and rodent kidneys (113, 114), and damage, they also have strong proangiogenic properties and effects rodent models of progressive renal failure show loss in glomer- on murine and human EPCs (58, 91, 92, 93). Furthermore, rIL-1RN ular and tubular VEGF-A coinciding with loss of capillaries and (anakinra) has been used as antiangiogenic therapy in various dis- the subsequent development of glomerulosclerosis and interstitial eases. Part of the effects of IL-1b on angiogenesis are mediated fibrosis (115). In humans, pharmacologic inhibition of VEGF-A by guest on September 29, 2021 through the regulation of various proangiogenic factors, including during cancer treatment can lead to proteinuria and worsening VEGF-A (94, 95). IL-1 can induce increased VEGF-A synthe- kidney function (116). Glomerular and peritubular capillary rare- sis (96), and genes in a cluster of IL-1–related molecules, including faction is an important feature of disease progression in other con- IL-1RN, may regulate VEGF-induced angiogenesis (97). This may ditions, including diabetic nephropathy (117). Recently, a role for explain, at least in part, why the strongest responses in improvement VEGF-A contributing to the maintenance of glomerular or peri- of EPC/CAC function in the SLE cultures were observed with ad- tubular capillaries and renal tissue survival has been proposed in dition of IL-1b, as this molecule may have promoted upregulation of diabetes (118). Interestingly, other renal diseases, including mini- endogenous VEGF-A expression. IL-1b also plays a key role in mal change disease or idiopathic membranous nephritis, have not ischemia-induced neovascularization by mobilizing endothelial shown the reduction of tubulointerstitial VEGF-A, indicating that precursor cells in a VEGF-dependent manner, as well as by upreg- renal damage or proteinuria per se does not lead to downregulation ulating VEGF and VEGFR-2 expression on endothelial cells (98). of this molecule (118). This was confirmed in our study, in which The role of proinflammatory stimuli on the viability and function patients with ANCA-positive vasculitis and renal damage did not of EPCs is conflicting. Some studies have reported enhanced EPC display downregulation of VEGF-A or renal capillary dropout. death in inflammatory conditions (99), whereas others report in- Supporting our data, a recent study shows that decreased VEGF in creased endothelial differentiation (59). Our study does not address SLE renal tissue may predict short-term loss of kidney function the question of the effects of IL-1b modulation in a proinflammatory (119). setting, but, rather, in a proangiogenic setting in the absence of Various studies have also linked progression of renal disease to exogenous proinflammatory mediators. In this case, IL-1b (but certain IL-1RN polymorphisms that are associated to higher IL- not other proinflammatory cytokines) can induce substantial im- 1RN levels in the general population (120, 121). However, the provements in EPC/CAC differentiation and survival (55). In ad- exact mechanisms linking renal failure progression to high IL- dition, IL-1b inhibited the skewing of myeloid cells present in 1RN had not been characterized. Given the observations made in the proangiogenic culture from CACs to mature DCs (11, 100), our study, it is possible that the antiangiogenic effect of increased a phenomenon previously reported to be induced by IFN-a. IL-1RN further promotes a reduction in renal capillaries and ham- Whereas this may seem counterintuitive, as IL-1b is widely used pers renal perfusion. Therefore, reduced VEGF-A and IL-1RN to promote DC maturation, it is generally used in combination (potentially secondary to enhanced exposure to type I IFN levels with other proinflammatory cytokines (101–104). Previous studies in the kidney) may contribute to decreased endothelial survival have reported that IL-1b can impair maturation in DCs treated and angiogenesis and to progression of kidney damage. This hy- with rapamycin (105), but, to our knowledge, no other study had pothesis is supported by recent observations that type I IFNs examined the isolated effects of IL-1b treatment on DCs or dif- produced by resident renal cells promote end-organ disease in ferentiating monocytes. autoantibody-mediated glomerulonephritis (122), and that systemic The Journal of Immunology 4467 administration of IFN-a to lupus murine models worsens nephritis 15. Blanco, P., A. K. Palucka, M. Gill, V. Pascual, and J. Banchereau. 2001. In- (123). 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Table I. Demographic and clinical characteristics of patients

VARIABLE CONTROL n=21 SLE n=68

Females, % 16 ( %) 64 ( %)

Age, mean (SEM) 33.1 (2.5) 37 (5)

Disease activity, mean _____ 3.65 (0.6)

SLEDAI (SEM)

SLEDAI < 2, % _____ 40

SLEDAI >2, % _____ 60

Medications, % _____

Antimalarials _____ 44 ( )

Azathioprine _____ 2

Mycophenolate mofetil _____ 20

Cyclophosphamide _____ 1

Methotrexate _____ 6

Prednisone < 0.5 mg/kg/d _____ 31

Prednisone 0.5-1 mg/kd/d _____ 1

Prednisone > 1 mg/kg/d _____ 0

No immunosuppression _____ 6

Past or current lupus _____ 13 nephritis, %

---— indicates not applicable; Ab: antibody; SLEDAI: Systemic Lupus Erythematosus disease activity index; SEM: standard error of the mean Supplementary Table II: Clinical and Histological parameters of patients supplying kidney biopsies

SLE (15) ANCA+ vas (5) Control (5) Mean ± SEM Mean ± SEM Mean ± SEM Serum creatinine 2.820 ± 0.728 1.86 ± 0.832 0.88 ± 0.394 Protein (grams) in 24 hours 2.553 ± 0.660 1.48 ± 0.662 nd Mesangial proliferation (0-3) 1.533 ± 0.396 0 ± 0 0 ± 0 GBM thickness (0-2) 0.333 ± 0.086 0 ± 0 0 ± 0 global glomerulosclerosis 0.533 ± 0.138 2.6 ± 1.163 0 ± 0 (%glom) segmental glomerulo sclerosis 2 ± 0.516 0 ± 0 0 ± 0 (%glom) glomerular capillary necrosis 5 ± 1.291 19 ± 8.497 0 ± 0 (% glom) extracapillary proliferation 13.733 ± 3.546 21 ± 9.391 0 ± 0 (% glom) interstitial infiltration (0-3) 0.2 ± 0.052 1.4 ± 0.626 0 ± 0 interstitial fibrosis (0-3) 0 ± 0 0 ± 0 0 ± 0

Supplementary Table III

Gene expression data

2850 genes differentially regulated in the healthy control EPCs/CACs treated by IFN-α compared to non-treated (q-value < 0.01).

Gene ID Gene Symbol Fold-change q-value 5157 PDGFRL 14.42 0.000 85477 SCIN 10.83 0.002 1672 DEFB1 8.33 0.000 344018 FIGLA 7.93 0.001 51421 AMOTL2 6.87 0.000 83401 ELOVL3 6.84 0.000 81030 ZBP1 6.49 0.000 2766 GMPR 6.16 0.000 1573 CYP2J2 5.98 0.000 9865 KIAA0644 5.87 0.000 7051 TGM1 5.68 0.000 9023 CH25H 5.07 0.000 85441 PRIC285 5.04 0.000 84941 HSH2D 4.84 0.000 1588 CYP19A1 4.81 0.000 7098 TLR3 4.77 0.000 91624 NEXN 4.74 0.000 8900 CCNA1 4.50 0.000 3487 IGFBP4 4.41 0.001 8820 HESX1 4.39 0.000 51191 HERC5 4.30 0.000 3728 JUP 4.27 0.000 65987 KCTD14 4.20 0.000 3557 IL1RN 4.18 0.000 64762 FAM59A 4.05 0.000 114880 OSBPL6 4.01 0.009 23052 ENDOD1 3.93 0.000 55615 PRR5 3.86 0.001 83990 BRIP1 3.75 0.001 8638 OASL 3.72 0.000 80055 PGAP1 3.71 0.000 79730 NSUN7 3.67 0.000 165530 CLEC4F 3.66 0.000 339416 ANKRD45 3.64 0.000 79132 DHX58 3.59 0.000 87178 PNPT1 3.59 0.000 79827 ASAM 3.45 0.000 54979 HRASLS2 3.45 0.001 23586 DDX58 3.44 0.000 57648 KIAA1522 3.36 0.002 26471 NUPR1 3.35 0.000 55008 HERC6 3.34 0.000 1

221711 SYCP2L 3.34 0.002 9517 SPTLC2 3.29 0.000 23034 SAMD4A 3.25 0.000 2867 FFAR2 3.24 0.000 729034 LOC729034 3.24 0.000 257019 FRMD3 3.21 0.000 127254 C1orf173 3.17 0.000 85413 SLC22A16 3.15 0.000 57088 PLSCR4 3.10 0.000 4499 MT1M 3.04 0.000 152926 PPM1K 3.00 0.000 26228 STAP1 2.94 0.000 375346 TMEM110 2.93 0.000 1832 DSP 2.93 0.001 93082 LINCR 2.91 0.000 4600 MX2 2.91 0.000 151556 GPR155 2.90 0.000 54894 RNF43 2.86 0.000 5371 PML 2.85 0.000 3669 ISG20 2.84 0.000 199223 TTC21A 2.83 0.000 5939 RBMS2 2.80 0.000 2982 GUCY1A3 2.79 0.001 23380 SRGAP2 2.79 0.000 9910 RABGAP1L 2.77 0.000 114991 ZNF618 2.74 0.000 4599 MX1 2.74 0.000 51251 NT5C3 2.71 0.000 9674 KIAA0040 2.71 0.000 92745 SLC38A5 2.70 0.001 84628 NTNG2 2.69 0.000 255231 MCOLN2 2.69 0.000 64108 RTP4 2.68 0.000 84930 MASTL 2.67 0.000 165631 PARP15 2.66 0.000 143689 PIWIL4 2.63 0.000 84561 SLC12A8 2.60 0.000 159091 FAM122C 2.58 0.000 51471 NAT8B 2.57 0.000 3902 LAG3 2.57 0.001 8995 TNFSF18 2.57 0.001 873 CBR1 2.56 0.000 5608 MAP2K6 2.56 0.002 51513 ETV7 2.54 0.000 8548 BLZF1 2.54 0.000 9381 OTOF 2.53 0.000 201625 DNHD2 2.52 0.000 4939 OAS2 2.52 0.000 55084 SOBP 2.51 0.002 84251 SGIP1 2.50 0.003 3700 ITIH4 2.50 0.001 4343 MOV10 2.49 0.000

23424 TDRD7 2.46 0.000 51365 PLA1A 2.45 0.000 3667 IRS1 2.44 0.000 55501 CHST12 2.44 0.000 1466 CSRP2 2.44 0.003 25865 PRKD2 2.42 0.000 580 BARD1 2.41 0.000 3665 IRF7 2.41 0.000 7318 UBE1L 2.40 0.000 4938 OAS1 2.38 0.000 5420 PODXL 2.38 0.000 55711 MLSTD1 2.38 0.000 200316 APOBEC3F 2.38 0.000 1996 ELAVL4 2.37 0.000 113730 KLHDC7B 2.32 0.000 79370 BCL2L14 2.31 0.000 162394 SLFN5 2.30 0.000 3433 IFIT2 2.30 0.000 57493 HEG1 2.30 0.000 139324 HDX 2.30 0.000 10563 CXCL13 2.29 0.000 11277 TREX1 2.28 0.000 10076 PTPRU 2.28 0.000 9576 SPAG6 2.27 0.000 114879 OSBPL5 2.27 0.000 5979 RET 2.27 0.001 123872 LRRC50 2.27 0.003 89853 FAM125B 2.27 0.000 81622 UNC93B1 2.26 0.000 11262 SP140 2.26 0.000 128025 WDR64 2.25 0.009 132864 CPEB2 2.25 0.000 27348 TOR1B 2.23 0.000 85363 TRIM5 2.23 0.000 91543 RSAD2 2.22 0.000 3437 IFIT3 2.22 0.000 117852 TRIMP1 2.22 0.000 54033 RBM11 2.22 0.001 116071 BATF2 2.20 0.000 1379 CR1L 2.20 0.001 389125 MUSTN1 2.20 0.000 6387 CXCL12 2.20 0.003 55603 FAM46A 2.18 0.000 1152 CKB 2.18 0.000 388228 SBK1 2.17 0.000 727 C5 2.17 0.000 117854 TRIM6 2.17 0.000 375287 RBM43 2.16 0.000 3434 IFIT1 2.16 0.000 55337 FLJ11286 2.15 0.000 83642 RP3-402G11.5 2.15 0.000 26010 LOC26010 2.15 0.000

9636 ISG15 2.14 0.000 952 CD38 2.13 0.001 441108 LOC441108 2.12 0.000 5618 PRLR 2.12 0.000 57228 LOC57228 2.12 0.000 8743 TNFSF10 2.12 0.000 57489 ODF2L 2.11 0.000 65220 NADK 2.10 0.000 3431 SP110 2.10 0.000 2650 GCNT1 2.10 0.000 54809 SAMD9 2.09 0.000 134285 TMEM171 2.09 0.000 135112 NCOA7 2.09 0.000 84875 PARP10 2.08 0.000 2526 FUT4 2.07 0.000 5581 PRKCE 2.07 0.000 146857 SLFN13 2.07 0.000 729810 LOC729810 2.07 0.000 83854 ANGPTL6 2.06 0.000 57169 ZNFX1 2.06 0.000 6373 CXCL11 2.05 0.000 116843 C6orf192 2.05 0.000 169693 C9orf71 2.04 0.000 55300 PI4K2B 2.03 0.000 23070 KIAA0082 2.02 0.000 25861 DFNB31 2.00 0.001 57639 KIAA1505 2.00 0.002 375035 SFT2D2 2.00 0.000 91937 TIMD4 1.99 0.001 57194 ATP10A 1.99 0.000 353514 LILRA5 1.99 0.000 4651 MYO10 1.98 0.000 91351 FLJ31033 1.98 0.000 200315 APOBEC3A 1.98 0.003 10970 CKAP4 1.98 0.000 6672 SP100 1.97 0.000 222255 ATXN7L1 1.97 0.001 94120 SYTL3 1.97 0.000 57758 SCUBE2 1.96 0.001 55281 TMEM140 1.96 0.000 2069 EREG 1.96 0.000 5129 PCTK3 1.96 0.000 54988 FLJ20581 1.95 0.000 653464 SRGAP2P1 1.95 0.000 53826 FXYD6 1.95 0.000 57699 CPNE5 1.95 0.001 9033 PKD2L1 1.95 0.001 51284 TLR7 1.94 0.000 1028 CDKN1C 1.94 0.000 3601 IL15RA 1.94 0.000 286334 LOC286334 1.94 0.000 9447 AIM2 1.93 0.000

10616 RBCK1 1.93 0.000 6894 TARBP1 1.93 0.000 254228 FAM26E 1.93 0.000 197259 MLKL 1.93 0.000 467 ATF3 1.92 0.000 9711 KIAA0226 1.92 0.000 57458 TMCC3 1.92 0.000 23338 PHF15 1.92 0.000 143630 UBQLNL 1.92 0.000 256380 SCML4 1.91 0.002 121551 BTBD11 1.91 0.006 7706 TRIM25 1.91 0.000 59 ACTA2 1.90 0.002 2191 FAP 1.90 0.000 4061 LY6E 1.89 0.002 55225 RAVER2 1.89 0.000 9567 GTPBP1 1.89 0.000 3458 IFNG 1.88 0.002 9881 LBA1 1.88 0.000 22982 DIP2C 1.88 0.003 139285 FAM123B 1.87 0.000 6539 SLC6A12 1.87 0.010 941 CD80 1.86 0.000 3430 IFI35 1.86 0.000 23347 SMCHD1 1.86 0.000 56913 C1GALT1 1.85 0.000 7290 HIRA 1.85 0.000 25841 ABTB2 1.85 0.000 154214 RNF217 1.84 0.000 9830 TRIM14 1.84 0.000 23033 DOPEY1 1.83 0.000 114876 OSBPL1A 1.83 0.000 55689 YEATS2 1.83 0.000 219285 SAMD9L 1.83 0.000 11044 POLS 1.83 0.000 11145 HRASLS3 1.83 0.002 1316 KLF6 1.83 0.000 4481 MSR1 1.82 0.000 356 FASLG 1.81 0.001 115361 GBP4 1.81 0.003 256227 MGC87042 1.81 0.001 8269 TMEM187 1.81 0.000 256236 NAPSB 1.80 0.001 10737 RFPL3S 1.80 0.000 259307 IL4I1 1.80 0.000 81894 SLC25A28 1.79 0.000 573 BAG1 1.79 0.000 55014 STX17 1.79 0.000 132320 SCLT1 1.79 0.000 957 ENTPD5 1.79 0.000 30812 SOX8 1.78 0.002 23400 ATP13A2 1.78 0.001

10855 HPSE 1.78 0.006 84000 TMPRSS13 1.78 0.000 55106 SLFN12 1.78 0.000 23432 GPR161 1.78 0.000 57130 ATP13A1 1.78 0.000 684 BST2 1.78 0.000 10589 DRAP1 1.77 0.000 57097 PARP11 1.77 0.000 84441 MAML2 1.77 0.000 5883 RAD9A 1.77 0.000 6752 SSTR2 1.77 0.000 54877 ZCCHC2 1.77 0.000 64651 AXUD1 1.77 0.000 81698 C15orf5 1.76 0.001 153684 LOC153684 1.76 0.000 26270 FBXO6 1.76 0.000 4940 OAS3 1.76 0.000 5332 PLCB4 1.76 0.009 11000 SLC27A3 1.76 0.001 3977 LIFR 1.76 0.001 51493 C22orf28 1.76 0.000 92797 HELB 1.76 0.001 6238 RRBP1 1.76 0.000 4582 MUC1 1.75 0.002 215 ABCD1 1.74 0.001 201175 LOC201175 1.74 0.003 55509 SNFT 1.74 0.006 644 BLVRA 1.74 0.000 92170 MTG1 1.73 0.000 57714 KIAA1618 1.73 0.000 151306 GPBAR1 1.73 0.000 51427 ZNF107 1.73 0.000 1240 CMKLR1 1.73 0.000 688 KLF5 1.72 0.001 728769 LOC728769 1.72 0.000 80021 TMEM62 1.71 0.000 54676 GTPBP2 1.71 0.000 24145 PANX1 1.71 0.000 92092 ZC3HAV1L 1.70 0.000 54847 SIDT1 1.70 0.000 114801 KIAA1913 1.69 0.002 160897 GPR180 1.69 0.000 634 CEACAM1 1.69 0.000 10188 TNK2 1.69 0.000 285761 DCBLD1 1.69 0.002 400941 FLJ42418 1.68 0.003 166379 BBS12 1.68 0.000 7286 TUFT1 1.68 0.002 10993 SDS 1.68 0.003 9610 RIN1 1.68 0.001 390 RND3 1.68 0.003 6354 CCL7 1.68 0.001

9315 C5orf13 1.68 0.000 55026 FAM70A 1.67 0.002 23273 KIAA0367 1.67 0.002 400077 FLJ42957 1.67 0.002 79792 GSDMDC1 1.67 0.002 29761 USP25 1.67 0.000 24138 IFIT5 1.67 0.000 3965 LGALS9 1.66 0.000 6398 SECTM1 1.66 0.000 59345 GNB4 1.66 0.000 843 CASP10 1.66 0.000 629 CFB 1.66 0.007 65979 PHACTR4 1.66 0.000 221421 C6orf206 1.66 0.000 147645 LOC147645 1.66 0.000 8717 TRADD 1.66 0.001 115004 C6orf150 1.66 0.000 127396 ZNF684 1.66 0.000 317649 EIF4E3 1.65 0.001 4086 SMAD1 1.65 0.000 2820 GPD2 1.65 0.000 51807 TUBA8 1.65 0.000 10046 CXorf6 1.65 0.007 157983 C9orf66 1.64 0.002 8542 APOL1 1.64 0.000 246778 IL27 1.64 0.002 83857 TMTC1 1.64 0.001 729839 LOC729839 1.63 0.000 2281 FKBP1B 1.63 0.002 79570 FAM77C 1.63 0.004 6876 TAGLN 1.63 0.000 7850 IL1R2 1.63 0.002 4332 MNDA 1.63 0.000 81844 TRIM56 1.63 0.000 79094 CHAC1 1.63 0.006 644695 LOC644695 1.63 0.006 1267 CNP 1.63 0.000 23165 NUP205 1.62 0.000 170482 CLEC4C 1.62 0.007 8814 CDKL1 1.62 0.000 85440 DOCK7 1.62 0.000 9997 SCO2 1.62 0.000 51314 TXNDC3 1.62 0.000 3717 JAK2 1.62 0.000 200942 KLHDC8B 1.62 0.009 83988 NCALD 1.62 0.000 558 AXL 1.62 0.000 10644 IGF2BP2 1.62 0.009 10391 CORO2B 1.62 0.004 5610 EIF2AK2 1.62 0.000 2015 EMR1 1.62 0.009 132321 C4orf33 1.61 0.000

56987 BBX 1.61 0.001 55601 FLJ20035 1.61 0.000 342035 GLDN 1.61 0.000 78998 C8orf51 1.61 0.007 80017 C14orf159 1.61 0.000 430 ASCL2 1.61 0.002 22809 ATF5 1.61 0.000 10392 NOD1 1.61 0.000 25923 DKFZP564J0863 1.60 0.000 5414 39695 1.60 0.000 54507 ADAMTSL4 1.60 0.000 11074 TRIM31 1.60 0.000 27185 DISC1 1.60 0.000 51309 ARMCX1 1.60 0.000 5819 PVRL2 1.60 0.000 51422 PRKAG2 1.60 0.000 4012 LNPEP 1.59 0.000 143888 KDELC2 1.59 0.001 84560 MT4 1.59 0.003 2869 GRK5 1.59 0.002 116443 GRIN3A 1.59 0.000 4254 KITLG 1.59 0.003 28797 IGLV3-19 1.59 0.001 283 ANG 1.59 0.002 51316 PLAC8 1.59 0.002 55512 SMPD3 1.59 0.001 8676 STX11 1.59 0.001 85315 PAQR8 1.58 0.000 355 FAS 1.58 0.001 6641 SNTB1 1.58 0.000 51479 ANKFY1 1.58 0.000 5763 PTMS 1.58 0.003 118421 C21orf100 1.58 0.001 971 CD72 1.58 0.002 9027 NAT8 1.57 0.000 80176 SPSB1 1.57 0.000 6737 TRIM21 1.57 0.000 10561 IFI44 1.57 0.000 54536 EXOC6 1.57 0.001 8464 SUPT3H 1.57 0.003 51338 MS4A4A 1.57 0.007 387032 ZKSCAN4 1.56 0.000 10499 NCOA2 1.56 0.003 197135 LOC197135 1.56 0.000 10581 IFITM2 1.56 0.002 10964 IFI44L 1.56 0.001 8775 NAPA 1.56 0.000 79993 ELOVL7 1.56 0.000 54097 FAM3B 1.56 0.001 3600 IL15 1.55 0.000 5359 PLSCR1 1.55 0.000 84335 AKT1S1 1.55 0.000

140691 TRIM69 1.55 0.001 26133 TRPC4AP 1.55 0.001 8528 DDO 1.55 0.002 578 BAK1 1.55 0.003 5875 RABGGTA 1.55 0.000 8737 RIPK1 1.55 0.000 6509 SLC1A4 1.55 0.002 9641 IKBKE 1.55 0.000 81857 MED25 1.54 0.002 1534 CYB561 1.54 0.000 3595 IL12RB2 1.54 0.009 84547 PGBD1 1.54 0.006 84290 CAPNS2 1.54 0.001 49855 SCAPER 1.54 0.003 23414 ZFPM2 1.54 0.002 144423 GLT1D1 1.54 0.002 54530 C1orf218 1.54 0.002 51131 PHF11 1.54 0.000 9603 NFE2L3 1.53 0.000 23064 SETX 1.53 0.000 57801 HES4 1.53 0.003 284004 HEXDC 1.53 0.002 57706 DENND1A 1.53 0.003 7726 TRIM26 1.53 0.000 4502 MT2A 1.53 0.002 6993 DYNLT1 1.53 0.000 2131 EXT1 1.53 0.001 348110 C15orf38 1.52 0.000 1393 CRHBP 1.52 0.003 389289 C5orf39 1.52 0.005 6715 SRD5A1 1.52 0.000 9683 N4BP1 1.52 0.000 57643 ZSWIM5 1.52 0.001 152877 FAM53A 1.52 0.007 10482 NXF1 1.52 0.000 4493 MT1E 1.52 0.003 11035 RIPK3 1.52 0.001 23682 RAB38 1.52 0.002 55876 GSDML 1.52 0.003 1140 CHRNB1 1.52 0.002 10403 NDC80 1.51 0.001 28912 IGKV3-20 1.51 0.001 26750 RPS6KC1 1.51 0.000 219988 FLJ36874 1.51 0.000 201176 ARHGAP27 1.51 0.000 57576 KIF17 1.51 0.006 6546 SLC8A1 1.51 0.003 51303 FKBP11 1.51 0.005 63875 MRPL17 1.51 0.000 141 ADPRH 1.51 0.000 64327 LMBR1 1.51 0.003 116285 ACSM1 1.50 0.002

9399 STOML1 1.50 0.000 10435 CDC42EP2 1.50 0.001 54739 XAF1 1.50 0.000 1890 ECGF1 1.50 0.000 7130 TNFAIP6 1.50 0.004 153020 RASGEF1B 1.50 0.000 825 CAPN3 1.50 0.000 3574 IL7 1.50 0.002 57589 KIAA1432 1.50 0.000 6654 SOS1 1.50 0.000 7068 THRB 1.50 0.001 3384 ICAM2 1.50 0.001 64343 AZI2 1.50 0.000 11135 CDC42EP1 1.50 0.001 1117 CHI3L2 1.50 0.007 5520 PPP2R2A 1.49 0.000 23108 GARNL4 1.49 0.007 286122 C8orf31 1.49 0.007 10791 VAMP5 1.49 0.002 54734 RAB39 1.49 0.000 3310 HSPA6 1.49 0.005 29121 CLEC2D 1.49 0.001 23086 EXPH5 1.49 0.001 84838 ZNF496 1.49 0.000 7280 TUBB2A 1.49 0.001 80830 APOL6 1.49 0.000 8526 DGKE 1.49 0.007 64173 SPATA1 1.49 0.002 4005 LMO2 1.49 0.000 79056 PRRG4 1.49 0.002 7849 PAX8 1.48 0.001 80174 DBF4B 1.48 0.001 473 RERE 1.48 0.000 29760 BLNK 1.48 0.000 64135 IFIH1 1.48 0.000 4615 MYD88 1.48 0.000 23597 ACOT9 1.48 0.000 4192 MDK 1.48 0.003 28815 IGLV2-14 1.48 0.009 659 BMPR2 1.48 0.000 26034 PIP3-E 1.47 0.003 222161 DKFZp586I1420 1.47 0.000 54438 GFOD1 1.47 0.000 26277 TINF2 1.47 0.000 56938 ARNTL2 1.47 0.001 246329 STAC3 1.47 0.008 55234 SMU1 1.47 0.001 255783 LOC255783 1.47 0.007 1608 DGKG 1.47 0.002 28822 IGLV1-47 1.47 0.003 10133 OPTN 1.47 0.002 54936 ADPRHL2 1.47 0.000

7779 SLC30A1 1.47 0.001 3620 INDO 1.47 0.009 7006 TEC 1.47 0.001 10734 STAG3 1.47 0.004 64689 GORASP1 1.46 0.000 23566 EDG7 1.46 0.005 219537 SMTNL1 1.46 0.006 10603 SH2B2 1.46 0.001 162517 FBXO39 1.46 0.001 54464 XRN1 1.46 0.000 29126 CD274 1.46 0.003 375056 MIA3 1.46 0.000 55626 FLJ20294 1.46 0.000 64853 C1orf80 1.46 0.000 2185 PTK2B 1.46 0.000 84333 PCGF5 1.46 0.000 10859 LILRB1 1.46 0.000 5664 PSEN2 1.46 0.001 51280 GOLM1 1.46 0.003 55802 DCP1A 1.46 0.000 51237 MGC29506 1.46 0.005 9414 TJP2 1.45 0.003 57153 SLC44A2 1.45 0.009 8303 SNN 1.45 0.004 23547 LILRA4 1.45 0.007 55072 RNF31 1.45 0.000 400709 SIGLECP16 1.45 0.001 9725 TMEM63A 1.45 0.002 64780 MICAL1 1.45 0.001 283129 LOC283129 1.45 0.003 115825 WDFY2 1.44 0.000 8837 CFLAR 1.44 0.001 81553 FAM49A 1.44 0.002 9749 PHACTR2 1.44 0.000 57419 SLC24A3 1.44 0.009 23177 CEP68 1.44 0.001 23214 XPO6 1.44 0.000 9465 AKAP7 1.44 0.000 643866 CBLN3 1.44 0.000 51393 TRPV2 1.44 0.000 4210 MEFV 1.44 0.003 969 CD69 1.44 0.000 4117 MAK 1.44 0.000 4299 AFF1 1.44 0.000 9957 HS3ST1 1.43 0.001 135932 TMEM139 1.43 0.003 29935 RPA4 1.43 0.009 9814 SFI1 1.43 0.007 26002 MOXD1 1.43 0.002 6773 STAT2 1.43 0.000 3586 IL10 1.43 0.007 22901 ARSG 1.43 0.002

836 CASP3 1.43 0.002 912 CD1D 1.43 0.007 5996 RGS1 1.43 0.000 10865 ARID5A 1.43 0.001 113277 TMEM106A 1.43 0.000 80231 CXorf21 1.43 0.001 56911 C21orf7 1.43 0.009 93185 IGSF8 1.43 0.006 10346 TRIM22 1.42 0.000 145864 HAPLN3 1.42 0.006 4752 NEK3 1.42 0.001 375387 LRRC33 1.42 0.000 10739 RFPL2 1.42 0.005 9961 MVP 1.42 0.000 256586 LYSMD2 1.42 0.000 2887 GRB10 1.42 0.001 7405 UVRAG 1.42 0.000 9473 C1orf38 1.42 0.000 53917 RAB24 1.42 0.006 51177 PLEKHO1 1.41 0.000 10013 HDAC6 1.41 0.000 375790 AGRN 1.41 0.003 57590 WDFY1 1.41 0.000 55020 FLJ20699 1.41 0.000 730249 LOC730249 1.41 0.006 157638 FAM84B 1.41 0.001 63916 ELMO2 1.41 0.000 153222 LOC153222 1.41 0.001 130589 GALM 1.41 0.002 9014 TAF1B 1.41 0.000 8877 SPHK1 1.41 0.004 145567 TTC7B 1.41 0.000 10208 USPL1 1.41 0.000 7221 TRPC2 1.41 0.001 8850 PCAF 1.41 0.002 23786 BCL2L13 1.41 0.000 221079 ARL5B 1.41 0.000 27074 LAMP3 1.41 0.002 84162 KIAA1109 1.41 0.002 23077 MYCBP2 1.41 0.000 51606 ATP6V1H 1.41 0.000 283377 SPRYD4 1.41 0.000 29071 C1GALT1C1 1.41 0.000 83638 C11orf68 1.40 0.000 80124 VCPIP1 1.40 0.000 4067 LYN 1.40 0.000 4616 GADD45B 1.40 0.001 2591 GALNT3 1.40 0.006 9587 MAD2L1BP 1.40 0.000 9826 ARHGEF11 1.40 0.000 128272 ARHGEF19 1.40 0.005 11054 OGFR 1.40 0.001

159013 CXorf38 1.40 0.001 5214 PFKP 1.40 0.002 80821 DDHD1 1.40 0.000 27075 TSPAN13 1.40 0.001 783 CACNB2 1.40 0.000 389 RHOC 1.40 0.000 56829 ZC3HAV1 1.39 0.001 28395 IGHV4-34 1.39 0.001 7016 TESK1 1.39 0.003 1441 CSF3R 1.39 0.001 5732 PTGER2 1.39 0.001 55803 CENTA2 1.39 0.002 10738 RFPL3 1.39 0.002 7402 UTRN 1.39 0.002 83666 PARP9 1.39 0.000 8061 FOSL1 1.39 0.003 79668 PARP8 1.39 0.002 10903 MTMR11 1.39 0.001 54823 C1orf26 1.38 0.003 64761 PARP12 1.38 0.000 9840 KIAA0748 1.38 0.009 5905 RANGAP1 1.38 0.000 8291 DYSF 1.38 0.001 113829 SLC35A4 1.38 0.000 51439 FAM8A1 1.38 0.000 29990 PILRB 1.38 0.006 55620 STAP2 1.38 0.009 11011 TLK2 1.38 0.002 55770 EXOC2 1.38 0.002 28825 IGLV1-40 1.38 0.003 79973 ZNF442 1.38 0.009 23630 KCNE1L 1.37 0.006 5638 PRRG1 1.37 0.003 1847 DUSP5 1.37 0.002 10475 TRIM38 1.37 0.003 57224 NHSL1 1.37 0.000 127703 C1orf216 1.37 0.002 117289 TAGAP 1.37 0.000 3784 KCNQ1 1.37 0.003 26256 CABYR 1.37 0.001 84132 USP42 1.37 0.000 10943 MSL3L1 1.37 0.003 10518 CIB2 1.37 0.002 57609 DIP2B 1.37 0.000 54149 C21orf91 1.37 0.002 54020 SLC37A1 1.37 0.003 54900 LAX1 1.37 0.002 54869 EPS8L1 1.37 0.003 25780 RASGRP3 1.37 0.001 344887 LOC344887 1.37 0.001 134111 FLJ25076 1.37 0.003 80012 PHC3 1.36 0.002

1375 CPT1B 1.36 0.002 1992 SERPINB1 1.36 0.002 2618 GART 1.36 0.002 151195 CCNYL1 1.36 0.000 64127 NOD2 1.36 0.000 400223 FLJ39779 1.36 0.003 54749 EPDR1 1.36 0.004 5899 RALB 1.36 0.000 56259 CTNNBL1 1.36 0.000 64121 RRAGC 1.36 0.000 56950 SMYD2 1.36 0.009 4144 MAT2A 1.36 0.001 2175 FANCA 1.36 0.001 51100 SH3GLB1 1.36 0.000 26037 SIPA1L1 1.36 0.005 8519 IFITM1 1.36 0.007 8496 PPFIBP1 1.36 0.001 23348 DOCK9 1.36 0.003 195827 C9orf21 1.35 0.003 94240 EPSTI1 1.35 0.000 51701 NLK 1.35 0.001 126321 C19orf28 1.35 0.002 84225 ZMYND15 1.35 0.002 26030 PLEKHG3 1.35 0.007 5393 EXOSC9 1.35 0.003 57636 ARHGAP23 1.35 0.002 23623 RUSC1 1.35 0.000 2180 ACSL1 1.35 0.000 137075 CLDN23 1.35 0.002 7368 UGT8 1.35 0.009 387921 RP11-50D16.3 1.35 0.001 6258 RXRG 1.35 0.002 9079 LDB2 1.35 0.009 23426 GRIP1 1.35 0.010 84271 POLDIP3 1.35 0.000 28820 IGLV1-51 1.35 0.008 91289 TMEM112B 1.35 0.001 83547 RILP 1.35 0.001 93349 LOC93349 1.34 0.000 9844 ELMO1 1.34 0.003 8869 ST3GAL5 1.34 0.000 5524 PPP2R4 1.34 0.003 92906 HNRPLL 1.34 0.002 6741 SSB 1.34 0.000 53836 GPR87 1.34 0.001 5891 RAGE 1.34 0.001 6314 ATXN7 1.34 0.002 57146 TMEM159 1.34 0.009 84433 CARD11 1.34 0.001 3444 IFNA7 1.34 0.007 22902 RUFY3 1.34 0.003 221037 JMJD1C 1.34 0.000

9325 TRIP4 1.34 0.001 140739 UBE2F 1.34 0.005 11080 DNAJB4 1.34 0.001 127544 RNF19B 1.34 0.000 57674 RNF213 1.34 0.000 30009 TBX21 1.33 0.002 6626 SNRPA 1.33 0.001 167153 PAPD4 1.33 0.000 84868 HAVCR2 1.33 0.002 64097 EPB41L4A 1.33 0.009 4205 MEF2A 1.33 0.001 6891 TAP2 1.33 0.003 203522 DDX26B 1.33 0.002 7091 TLE4 1.33 0.000 4088 SMAD3 1.33 0.001 7453 WARS 1.33 0.003 79657 RPAP3 1.33 0.002 2651 GCNT2 1.33 0.000 5970 RELA 1.33 0.002 824 CAPN2 1.33 0.000 9672 SDC3 1.33 0.002 8848 TSC22D1 1.33 0.002 5152 PDE9A 1.33 0.001 7403 UTX 1.33 0.001 23645 PPP1R15A 1.33 0.001 54897 CASZ1 1.33 0.009 54467 ANKIB1 1.33 0.002 346653 FAM137B 1.32 0.003 60672 RP5-1077B9.4 1.32 0.000 284086 NEK8 1.32 0.007 8462 KLF11 1.32 0.000 80162 ATHL1 1.32 0.005 23607 CD2AP 1.32 0.000 51092 SIDT2 1.32 0.000 285237 C3orf38 1.32 0.001 23143 LRCH1 1.32 0.001 7072 TIA1 1.32 0.003 55577 NAGK 1.32 0.000 987 LRBA 1.32 0.010 3428 IFI16 1.32 0.000 55593 OTUD5 1.32 0.001 148022 TICAM1 1.32 0.003 94039 ZNF101 1.32 0.004 253018 HCG27 1.32 0.009 253190 SERHL2 1.32 0.007 2701 GJA4 1.32 0.002 2762 GMDS 1.32 0.002 1390 CREM 1.32 0.002 112869 CCDC101 1.32 0.000 79932 KIAA0319L 1.32 0.000 114787 GPRIN1 1.32 0.002 9362 CPNE6 1.32 0.007

3635 INPP5D 1.31 0.000 79716 NPEPL1 1.31 0.001 28908 IGKV4-1 1.31 0.004 2137 EXTL3 1.31 0.000 7767 ZNF224 1.31 0.000 340596 LHFPL1 1.31 0.003 23216 TBC1D1 1.31 0.002 79834 SGK269 1.31 0.001 8450 CUL4B 1.31 0.000 26071 FAM127B 1.31 0.003 29919 C18orf8 1.31 0.001 131601 GPR175 1.31 0.007 113510 HEL308 1.31 0.000 9958 USP15 1.31 0.001 80018 C12orf30 1.31 0.000 7205 TRIP6 1.31 0.002 84955 NUDCD1 1.31 0.001 3957 LGALS2 1.31 0.003 4353 MPO 1.31 0.009 55194 C1orf78 1.31 0.005 55114 ARHGAP17 1.31 0.002 124446 LOC124446 1.31 0.001 1636 ACE 1.30 0.006 30844 EHD4 1.30 0.000 55013 CCDC109B 1.30 0.003 84174 SLA2 1.30 0.001 401494 PTPLAD2 1.30 0.006 6533 SLC6A6 1.30 0.004 800 CALD1 1.30 0.003 5739 PTGIR 1.30 0.002 79758 DHRS12 1.30 0.002 55839 CENPN 1.30 0.007 28776 IGLV7-43 1.30 0.004 9034 CCRL2 1.30 0.000 8233 ZRSR2 1.30 0.002 3097 HIVEP2 1.30 0.010 54625 PARP14 1.30 0.000 201475 RAB12 1.30 0.010 54947 AYTL1 1.30 0.001 26509 FER1L3 1.30 0.004 840 CASP7 1.30 0.001 29767 TMOD2 1.30 0.002 23649 POLA2 1.29 0.001 10673 TNFSF13B 1.29 0.000 81704 DOCK8 1.29 0.003 85007 AGXT2L2 1.29 0.004 239 ALOX12 1.29 0.009 170384 FUT11 1.29 0.006 9886 RHOBTB1 1.29 0.002 3112 HLA-DOB 1.29 0.002 9531 BAG3 1.29 0.009 7186 TRAF2 1.29 0.007

283152 LOC283152 1.29 0.001 3418 IDH2 1.29 0.010 10010 TANK 1.29 0.000 27351 D15Wsu75e 1.29 0.004 114818 KLHL29 1.29 0.009 5032 P2RY11 1.29 0.003 11021 RAB35 1.29 0.004 51466 EVL 1.29 0.003 60386 SLC25A19 1.29 0.003 2005 ELK4 1.29 0.002 9969 MED13 1.29 0.004 10307 APBB3 1.29 0.008 54453 RIN2 1.29 0.001 154075 SAMD3 1.29 0.002 3779 KCNMB1 1.29 0.003 148932 MOBKL2C 1.28 0.002 11179 ZNF277P 1.28 0.003 124222 PAQR4 1.28 0.005 9246 UBE2L6 1.28 0.000 55716 LMBR1L 1.28 0.002 84069 PLEKHN1 1.28 0.001 1889 ECE1 1.28 0.002 57494 FAM80B 1.28 0.003 51129 ANGPTL4 1.28 0.002 91252 SLC39A13 1.28 0.001 57117 INTS12 1.28 0.001 23549 DNPEP 1.28 0.003 53335 BCL11A 1.28 0.000 9111 NMI 1.28 0.000 221749 C6orf145 1.28 0.005 11133 KPTN 1.28 0.001 5580 PRKCD 1.28 0.002 80112 WBSCR23 1.28 0.003 4276 MICA 1.28 0.001 3976 LIF 1.28 0.007 7069 THRSP 1.28 0.008 5930 RBBP6 1.28 0.000 4850 CNOT4 1.28 0.000 6355 CCL8 1.27 0.002 2332 FMR1 1.27 0.001 5049 PAFAH1B2 1.27 0.003 79627 OGFRL1 1.27 0.004 4683 NBN 1.27 0.001 5730 PTGDS 1.27 0.006 64218 SEMA4A 1.27 0.002 8705 B3GALT4 1.27 0.007 65056 GPBP1 1.27 0.001 8454 CUL1 1.27 0.000 79802 KIAA1822L 1.27 0.005 22996 C1orf34 1.27 0.002 834 CASP1 1.27 0.001 3364 HUS1 1.27 0.000

6674 SPAG1 1.27 0.003 2648 GCN5L2 1.27 0.001 118788 PIK3AP1 1.27 0.001 51023 MRPS18C 1.27 0.002 129880 BBS5 1.27 0.009 55701 FLJ10357 1.27 0.009 10241 CALCOCO2 1.27 0.003 79443 FYCO1 1.27 0.000 11006 LILRB4 1.27 0.002 896 CCND3 1.27 0.001 84248 FYTTD1 1.27 0.002 10678 B3GNT2 1.27 0.001 26020 LRP10 1.26 0.001 2787 GNG5 1.26 0.000 25948 KBTBD2 1.26 0.000 10466 COG5 1.26 0.006 2550 GABBR1 1.26 0.002 1861 TOR1A 1.26 0.001 2635 GBP3 1.26 0.009 5937 RBMS1 1.26 0.007 64863 METTL4 1.26 0.002 22849 CPEB3 1.26 0.001 11067 C10orf10 1.26 0.005 5699 PSMB10 1.26 0.003 57217 TTC7A 1.26 0.002 60436 TGIF2 1.26 0.003 5698 PSMB9 1.26 0.000 118429 ANTXR2 1.26 0.001 5325 PLAGL1 1.26 0.003 50650 ARHGEF3 1.26 0.007 4534 MTM1 1.26 0.002 80173 IFT74 1.26 0.000 5586 PKN2 1.26 0.006 2797 GNRH2 1.26 0.010 8675 STX16 1.26 0.004 9856 KIAA0319 1.26 0.003 3836 KPNA1 1.26 0.001 55500 ETNK1 1.26 0.002 116028 C16orf75 1.26 0.010 80380 PDCD1LG2 1.26 0.004 55733 HHAT 1.25 0.001 3883 KRT33A 1.25 0.001 83890 SPATA9 1.25 0.002 63935 C20orf67 1.25 0.002 81796 SLCO5A1 1.25 0.002 773 CACNA1A 1.25 0.008 29992 PILRA 1.25 0.004 6776 STAT5A 1.25 0.001 56942 C16orf61 1.25 0.001 3140 MR1 1.25 0.001 6390 SDHB 1.25 0.001 57613 KIAA1467 1.25 0.006

11252 PACSIN2 1.25 0.002 51054 PLEKHA9 1.25 0.003 5683 PSMA2 1.25 0.009 4170 MCL1 1.25 0.000 404093 CUEDC1 1.25 0.004 9962 SLC23A2 1.25 0.001 4814 NINJ1 1.25 0.002 57409 MIF4GD 1.25 0.004 22930 RAB3GAP1 1.25 0.000 9373 PLAA 1.25 0.001 57393 TMEM27 1.25 0.009 23264 ZC3H7B 1.25 0.001 9367 RAB9A 1.25 0.001 57154 SMURF1 1.25 0.003 5799 PTPRN2 1.25 0.003 1737 DLAT 1.25 0.002 119 ADD2 1.25 0.007 50853 VILL 1.25 0.007 127428 C1orf83 1.25 0.010 9712 USP6NL 1.25 0.003 79803 HPS6 1.25 0.003 253260 RICTOR 1.25 0.001 29950 SERTAD1 1.25 0.000 11332 ACOT7 1.25 0.000 3663 IRF5 1.24 0.006 2959 GTF2B 1.24 0.000 5696 PSMB8 1.24 0.000 25793 FBXO7 1.24 0.001 84142 CCDC98 1.24 0.009 23508 TTC9 1.24 0.008 7538 ZFP36 1.24 0.001 9663 LPIN2 1.24 0.009 3908 LAMA2 1.24 0.001 63901 FAM111A 1.24 0.001 64976 MRPL40 1.24 0.000 56985 C17orf48 1.24 0.001 56850 GRIPAP1 1.24 0.001 5031 P2RY6 1.24 0.001 90268 FAM105B 1.24 0.000 10567 RABAC1 1.24 0.006 136895 C7orf31 1.24 0.002 29933 GPR132 1.24 0.003 10445 MCRS1 1.24 0.009 64398 MPP5 1.24 0.009 727869 LOC727869 1.24 0.009 27179 IL1F6 1.24 0.007 51274 KLF3 1.24 0.010 5533 PPP3CC 1.24 0.002 284346 ZNF575 1.24 0.002 254187 TSGA10IP 1.24 0.005 9278 ZBTB22 1.24 0.006 10379 ISGF3G 1.24 0.001

221078 NSUN6 1.24 0.001 2151 F2RL2 1.24 0.009 94134 ARHGAP12 1.24 0.003 8543 LMO4 1.23 0.002 10800 CYSLTR1 1.23 0.003 54496 PRMT7 1.23 0.004 64215 DNAJC1 1.23 0.006 54093 SETD4 1.23 0.001 57646 USP28 1.23 0.005 64091 POPDC2 1.23 0.000 26137 ZBTB20 1.23 0.009 10633 RASL10A 1.23 0.003 831 CAST 1.23 0.002 10906 TRAFD1 1.23 0.004 84215 ZNF541 1.23 0.003 51510 CHMP5 1.23 0.002 401093 hCG_1806964 1.23 0.002 157697 ERICH1 1.23 0.007 202500 TCTE1 1.23 0.003 64224 HERPUD2 1.23 0.001 135114 HINT3 1.23 0.009 79961 DENND2D 1.23 0.002 23279 NUP160 1.23 0.005 7040 TGFB1 1.23 0.007 3558 IL2 1.23 0.007 255043 TMEM86B 1.23 0.010 79631 EFTUD1 1.23 0.004 2535 FZD2 1.23 0.009 54948 MRPL16 1.22 0.002 55835 CENPJ 1.22 0.003 9829 DNAJC6 1.22 0.005 84883 AIFM2 1.22 0.010 79651 RHBDF2 1.22 0.005 2040 STOM 1.22 0.004 2962 GTF2F1 1.22 0.001 AFFX- #N/A 1.22 0.002 HUMISGF3A/M97935_MA 64222 TOR3A 1.22 0.003 64374 SIL1 1.22 0.001 11055 ZPBP 1.22 0.003 151827 LRRC34 1.22 0.010 140460 ASB7 1.22 0.003 55007 FAM118A 1.22 0.002 6643 SNX2 1.22 0.000 80824 DUSP16 1.22 0.007 154 ADRB2 1.22 0.007 8467 SMARCA5 1.22 0.003 2621 GAS6 1.22 0.009 1230 CCR1 1.22 0.002 1455 CSNK1G2 1.22 0.002 3837 KPNB1 1.22 0.001 89846 FGD3 1.22 0.008

63899 NSUN3 1.22 0.000 57120 GOPC 1.22 0.003 5128 PCTK2 1.22 0.001 7741 ZNF187 1.22 0.004 80262 C16orf70 1.22 0.005 6892 TAPBP 1.22 0.006 221061 C10orf38 1.22 0.010 1453 CSNK1D 1.22 0.001 2130 EWSR1 1.22 0.007 54850 FBXL12 1.21 0.004 9755 TBKBP1 1.21 0.007 80032 ZNF556 1.21 0.004 9488 PIGB 1.21 0.003 374969 CCDC23 1.21 0.006 55269 PSPC1 1.21 0.004 162979 ZNF342 1.21 0.007 23048 FNBP1 1.21 0.002 83692 CD99L2 1.21 0.003 3964 LGALS8 1.21 0.001 5991 RFX3 1.21 0.004 8973 CHRNA6 1.21 0.007 374395 LOC374395 1.21 0.003 4001 LMNB1 1.21 0.004 6468 FBXW4 1.21 0.002 55905 ZNF313 1.21 0.001 125488 C18orf17 1.21 0.009 25902 MTHFD1L 1.21 0.009 114822 RHPN1 1.21 0.009 9092 SART1 1.21 0.001 51225 ABI3 1.21 0.003 126526 C19orf47 1.21 0.005 81846 SBF2 1.21 0.006 6429 SFRS4 1.21 0.002 3660 IRF2 1.21 0.001 2120 ETV6 1.21 0.002 976 CD97 1.21 0.002 29102 RNASEN 1.21 0.001 4089 SMAD4 1.20 0.002 80208 SPG11 1.20 0.003 6788 STK3 1.20 0.002 9262 STK17B 1.20 0.003 115019 SLC26A9 1.20 0.005 64114 TMBIM1 1.20 0.005 55785 FGD6 1.20 0.009 57369 GJA9 1.20 0.003 128497 C20orf165 1.20 0.006 10116 FEM1B 1.20 0.002 54765 TRIM44 1.20 0.006 283991 FAM100B 1.20 0.003 3753 KCNE1 1.20 0.009 23636 NUP62 1.20 0.002 22839 DLGAP4 1.20 0.003

5256 PHKA2 1.20 0.007 4055 LTBR 1.20 0.006 51291 GMIP 1.20 0.004 152641 C4orf38 1.20 0.001 23303 KIF13B 1.20 0.007 5786 PTPRA 1.20 0.003 11129 SFRS16 1.20 0.004 55668 C14orf118 1.20 0.002 128637 TBC1D20 1.20 0.004 5025 P2RX4 1.20 0.004 23080 KIAA0241 1.20 0.006 91461 LOC91461 1.20 0.003 28971 C11orf67 1.20 0.002 51061 TXNDC11 1.20 0.003 222194 RSBN1L 1.20 0.002 22875 ENPP4 1.20 0.007 6811 STX5 1.20 0.006 257203 DSCR9 1.20 0.007 54621 FLJ20674 1.20 0.009 9592 IER2 1.20 0.001 4084 MXD1 1.20 0.003 25820 ARIH1 1.19 0.002 80314 EPC1 1.19 0.003 9411 ARHGAP29 1.19 0.007 22978 NT5C2 1.19 0.007 55088 C10orf118 1.19 0.001 5110 PCMT1 1.19 0.001 79981 FRMD1 1.19 0.007 55326 AGPAT5 1.19 0.007 5545 PRB4 1.19 0.007 6478 SIAH2 1.19 0.009 5971 RELB 1.19 0.004 3627 CXCL10 1.19 0.006 996 CDC27 1.19 0.002 27332 ZNF638 1.19 0.002 65080 MRPL44 1.19 0.001 4277 MICB 1.19 0.009 51224 TCEB3B 1.19 0.006 57597 BAHCC1 1.19 0.007 54707 ATPBD1B 1.19 0.005 65264 UBE2Z 1.19 0.004 2235 FECH 1.19 0.003 8567 MADD 1.19 0.004 4149 MAX 1.19 0.009 200014 CC2D1B 1.19 0.007 54619 CCNJ 1.19 0.009 25897 RNF19A 1.19 0.002 387647 LOC387647 1.18 0.003 55147 RBM23 1.18 0.002 1312 COMT 1.18 0.003 654487 SRG 1.18 0.009 1666 DECR1 1.18 0.001

64412 GZF1 1.18 0.009 83937 RASSF4 1.18 0.002 8204 NRIP1 1.18 0.001 662 BNIP1 1.18 0.004 4082 MARCKS 1.18 0.005 285299 LOC285299 1.18 0.009 1616 DAXX 1.18 0.004 608 TNFRSF17 1.18 0.010 1659 DHX8 1.18 0.006 78994 PRR14 1.18 0.007 644903 FLJ38668 1.18 0.009 55286 C4orf19 1.18 0.006 6890 TAP1 1.18 0.002 8030 CCDC6 1.18 0.005 28231 SLCO4A1 1.18 0.009 126014 OSCAR 1.18 0.003 161145 C14orf83 1.18 0.002 2153 F5 1.18 0.007 112849 C14orf149 1.18 0.007 8774 NAPG 1.18 0.004 58533 SNX6 1.18 0.003 26157 GIMAP2 1.18 0.007 79585 CORO7 1.18 0.009 23185 LARP5 1.18 0.003 56894 AGPAT3 1.17 0.008 55160 ARHGEF10L 1.17 0.005 11276 AP1GBP1 1.17 0.007 27233 SULT1C4 1.17 0.003 8776 MTMR1 1.17 0.009 10421 CD2BP2 1.17 0.004 50865 HEBP1 1.17 0.006 23154 NCDN 1.17 0.004 10254 STAM2 1.17 0.003 84951 TNS4 1.17 0.007 114793 FMNL2 1.17 0.009 88 ACTN2 1.17 0.006 23325 KIAA1033 1.17 0.002 23210 JMJD6 1.17 0.009 103 ADAR 1.17 0.002 5151 PDE8A 1.17 0.005 51667 NUB1 1.17 0.003 256643 CXorf23 1.17 0.009 9699 RIMS2 1.17 0.006 2803 GOLGA4 1.17 0.007 11270 NRM 1.17 0.007 6520 SLC3A2 1.17 0.010 23317 DNAJC13 1.17 0.006 10524 HTATIP 1.17 0.002 55183 RIF1 1.17 0.009 54440 CXorf9 1.17 0.010 6484 ST3GAL4 1.17 0.003 221477 C6orf89 1.17 0.009

84807 TA-NFKBH 1.17 0.007 56929 FEM1C 1.17 0.002 8208 CHAF1B 1.17 0.009 9208 LRRFIP1 1.17 0.002 6351 CCL4 1.17 0.007 9158 FIBP 1.17 0.005 221472 FGD2 1.16 0.003 84239 ATP13A4 1.16 0.007 286075 ZNF707 1.16 0.003 961 CD47 1.16 0.003 51526 C20orf111 1.16 0.002 26580 BSCL2 1.16 0.007 123720 WHDC1 1.16 0.000 2590 GALNT2 1.16 0.009 9694 TTC35 1.16 0.009 79713 TMEM149 1.16 0.007 23304 UBR2 1.16 0.004 55080 TAPBPL 1.16 0.009 407 ARR3 1.16 0.003 55521 TRIM36 1.16 0.007 1654 DDX3X 1.16 0.003 970 CD70 1.16 0.004 54108 CHRAC1 1.16 0.007 83931 STK40 1.15 0.006 440956 LOC440956 1.15 0.010 84752 MGC4655 1.15 0.009 6050 RNH1 1.15 0.009 170575 GIMAP1 1.15 0.003 221496 LEMD2 1.15 0.009 90324 CCDC97 1.15 0.008 23351 KIAA0323 1.15 0.010 10211 FLOT1 1.15 0.009 2961 GTF2E2 1.15 0.003 9491 PSMF1 1.15 0.005 28511 NKIRAS2 1.15 0.005 27013 C2orf24 1.15 0.009 83440 ADPGK 1.15 0.007 64788 TMEM112 1.15 0.010 9202 ZMYM4 1.15 0.001 23367 LARP1 1.15 0.003 9191 DEDD 1.15 0.009 54962 TIPIN 1.15 0.003 396 ARHGDIA 1.15 0.003 29117 BRD7 1.15 0.007 29959 NRBP1 1.15 0.009 10875 FGL2 1.15 0.004 85865 GTPBP10 1.15 0.006 54957 TXNL4B 1.15 0.009 7444 VRK2 1.14 0.003 9951 HS3ST4 1.14 0.004 80308 FLAD1 1.14 0.007 10892 MALT1 1.14 0.003

4794 NFKBIE 1.14 0.007 775 CACNA1C 1.14 0.009 2783 GNB2 1.14 0.007 644151 LOC644151 1.14 0.009 388394 RPRML 1.14 0.006 9993 DGCR2 1.14 0.010 148870 CCDC27 1.14 0.004 11120 BTN2A1 1.14 0.006 78992 YIPF2 1.14 0.007 3735 KARS 1.14 0.007 26271 FBXO5 1.13 0.010 3301 DNAJA1 1.13 0.010 56257 MEPCE 1.13 0.009 5888 RAD51 1.13 0.009 254013 MGC50559 1.13 0.005 83479 DDX59 1.13 0.003 6793 STK10 1.13 0.009 55096 FLJ10213 1.13 0.007 9334 B4GALT5 1.13 0.010 5686 PSMA5 1.13 0.010 1495 CTNNA1 1.13 0.007 79595 SAP130 1.13 0.007 9453 GGPS1 1.13 0.007 51056 LAP3 1.13 0.010 5333 PLCD1 1.13 0.007 64582 GPR135 1.13 0.007 8763 CD164 1.12 0.005 80025 PANK2 1.12 0.010 80179 MYOHD1 1.12 0.004 145553 MDP1 1.12 0.003 84537 C21orf69 1.12 0.007 30 ACAA1 1.12 0.006 6729 SRP54 1.12 0.006 155038 GIMAP8 1.11 0.007 7803 PTP4A1 1.11 0.009 5877 RABIF 1.11 0.009 389332 LOC389332 1.10 0.008 64718 UNKL 1.10 0.009 2213 FCGR2B 1.09 0.009 57092 PCNP 0.92 0.009 64864 RFXDC2 0.92 0.007 11100 HNRPUL1 0.92 0.009 3184 HNRPD 0.91 0.009 11345 GABARAPL2 0.91 0.009 51068 NMD3 0.91 0.006 25909 AHCTF1 0.91 0.010 10280 OPRS1 0.91 0.007 7277 TUBA4A 0.91 0.007 51002 TPRKB 0.91 0.009 9093 DNAJA3 0.91 0.007 6767 ST13 0.90 0.007 5203 PFDN4 0.90 0.009

84316 LSMD1 0.90 0.009 54469 ZFAND6 0.90 0.005 23394 ADNP 0.90 0.009 57325 CSRP2BP 0.90 0.007 92595 ZNF764 0.90 0.010 140901 STK35 0.90 0.010 6500 SKP1A 0.90 0.004 51012 SLMO2 0.90 0.006 2976 GTF3C2 0.90 0.004 10565 ARFGEF1 0.90 0.009 5253 PHF2 0.90 0.009 6418 SET 0.90 0.007 57826 RAP2C 0.90 0.006 65109 UPF3B 0.90 0.009 10914 PAPOLA 0.90 0.006 6426 SFRS1 0.90 0.009 150726 FBXO41 0.90 0.006 51388 NIP7 0.89 0.010 1265 CNN2 0.89 0.008 79691 QTRTD1 0.89 0.006 3416 IDE 0.89 0.007 79184 BRCC3 0.89 0.008 9919 SEC16A 0.89 0.007 5537 PPP6C 0.89 0.007 22863 KIAA0831 0.89 0.009 9731 KIAA0562 0.89 0.009 140461 ASB8 0.89 0.007 6138 RPL15 0.89 0.005 55179 FAIM 0.89 0.007 132949 AASDH 0.89 0.009 6782 STCH 0.89 0.007 7411 VBP1 0.89 0.009 29883 CNOT7 0.89 0.007 8562 DENR 0.89 0.007 162681 C18orf54 0.89 0.008 84950 PRPF38A 0.89 0.009 51727 CMPK 0.89 0.010 397 ARHGDIB 0.89 0.009 5510 PPP1R7 0.89 0.009 11051 NUDT21 0.89 0.004 122553 TRAPPC6B 0.89 0.009 1982 EIF4G2 0.89 0.005 10194 TSHZ1 0.89 0.007 80817 KIAA1712 0.89 0.003 56889 TM9SF3 0.89 0.005 25870 SUMF2 0.89 0.010 55421 C17orf85 0.89 0.008 23643 LY96 0.89 0.007 64328 XPO4 0.89 0.009 93183 PIGM 0.89 0.006 1615 DARS 0.89 0.007 10928 RALBP1 0.89 0.007

160760 PPTC7 0.89 0.007 51719 CAB39 0.89 0.009 9147 SDCCAG1 0.89 0.007 51631 LUC7L2 0.89 0.009 55164 SHQ1 0.89 0.003 64434 NOM1 0.89 0.010 5621 PRNP 0.89 0.005 221504 ZBTB9 0.88 0.007 9218 VAPA 0.88 0.007 27230 SERP1 0.88 0.002 8452 CUL3 0.88 0.006 493753 MGC52110 0.88 0.003 57448 BIRC6 0.88 0.007 10494 STK25 0.88 0.009 79840 NHEJ1 0.88 0.007 2010 EMD 0.88 0.006 522 ATP5J 0.88 0.008 55486 PARL 0.88 0.007 51340 CRNKL1 0.88 0.003 5984 RFC4 0.88 0.009 2746 GLUD1 0.88 0.007 9643 MORF4L2 0.88 0.007 58497 PRUNE 0.88 0.005 51075 TXNDC14 0.88 0.008 515 ATP5F1 0.88 0.009 54994 C20orf11 0.88 0.007 9553 MRPL33 0.88 0.009 54920 DUS2L 0.88 0.009 3281 HSBP1 0.88 0.010 5876 RABGGTB 0.88 0.006 9538 EI24 0.88 0.009 54968 TMEM70 0.88 0.005 310 ANXA7 0.88 0.003 79888 AYTL2 0.88 0.006 10363 HMG20A 0.88 0.006 6120 RPE 0.88 0.008 7764 ZNF217 0.88 0.004 348235 FAM33A 0.88 0.007 7257 TSNAX 0.88 0.007 84240 ZCCHC9 0.88 0.007 3094 HINT1 0.88 0.009 5436 POLR2G 0.88 0.010 1399 CRKL 0.88 0.006 26046 ZNF294 0.88 0.007 25864 ABHD14A 0.88 0.009 10618 TGOLN2 0.88 0.009 219743 TYSND1 0.88 0.007 4094 MAF 0.88 0.009 79768 C15orf29 0.88 0.003 11232 POLG2 0.88 0.006 7360 UGP2 0.88 0.009 26263 FBXO22 0.88 0.006

5828 PXMP3 0.88 0.010 57534 MIB1 0.88 0.007 7389 UROD 0.88 0.009 55049 C19orf60 0.88 0.007 23244 PDS5A 0.88 0.005 1545 CYP1B1 0.88 0.009 63908 NAPB 0.88 0.010 128 ADH5 0.88 0.007 6734 SRPR 0.88 0.003 1788 DNMT3A 0.88 0.006 51575 ESF1 0.88 0.006 57658 CALCOCO1 0.88 0.008 55003 PAK1IP1 0.88 0.008 734 OSGIN2 0.88 0.007 5579 PRKCB1 0.88 0.010 55845 C3orf10 0.88 0.009 57515 SERINC1 0.88 0.010 200845 KCTD6 0.88 0.006 1355 COX15 0.87 0.010 5869 RAB5B 0.87 0.009 11161 C14orf1 0.87 0.007 593 BCKDHA 0.87 0.006 8560 DEGS1 0.87 0.009 2288 FKBP4 0.87 0.006 84896 ATAD1 0.87 0.003 64426 SUDS3 0.87 0.006 51616 TAF9B 0.87 0.005 57711 ZNF529 0.87 0.008 10015 PDCD6IP 0.87 0.009 10636 RGS14 0.87 0.010 51629 SLC25A39 0.87 0.005 10641 TUSC4 0.87 0.010 285315 C3orf33 0.87 0.004 83695 C12orf32 0.87 0.006 900 CCNG1 0.87 0.005 5824 PEX19 0.87 0.010 29088 MRPL15 0.87 0.009 11222 MRPL3 0.87 0.005 4240 MFGE8 0.87 0.005 3796 KIF2A 0.87 0.007 9419 CRIPT 0.87 0.006 79086 C19orf42 0.87 0.003 2280 FKBP1A 0.87 0.007 11183 MAP4K5 0.87 0.006 4033 LRMP 0.87 0.008 3609 ILF3 0.87 0.004 84914 ZNF587 0.87 0.003 14 AAMP 0.87 0.009 284309 ZNF776 0.87 0.007 27240 SIT1 0.87 0.007 79576 NKAP 0.87 0.010 9791 PTDSS1 0.87 0.005

79161 C7orf23 0.87 0.009 223 ALDH9A1 0.87 0.006 7798 LUZP1 0.87 0.003 5636 PRPSAP2 0.87 0.008 7326 UBE2G1 0.87 0.003 53981 CPSF2 0.87 0.007 1351 COX8A 0.87 0.007 113201 CASC4 0.87 0.006 8658 TNKS 0.87 0.010 56270 WDR45L 0.87 0.005 55656 INTS8 0.87 0.003 55758 RCOR3 0.87 0.003 5296 PIK3R2 0.87 0.010 2997 GYS1 0.87 0.009 6731 SRP72 0.87 0.009 5116 PCNT 0.87 0.005 10632 ATP5L 0.87 0.009 23406 COTL1 0.87 0.009 1019 CDK4 0.87 0.006 23204 ARL6IP1 0.87 0.009 83932 C1orf124 0.87 0.009 54471 SMCR7L 0.87 0.007 84295 PHF6 0.87 0.009 4833 NME4 0.87 0.009 22984 PDCD11 0.87 0.009 26355 C3orf28 0.87 0.009 23075 SWAP70 0.87 0.009 6874 TAF4 0.87 0.006 8662 EIF3B 0.87 0.005 23518 R3HDM1 0.87 0.009 10276 NET1 0.87 0.009 51249 TMEM69 0.87 0.010 200895 DHFRL1 0.87 0.007 10550 ARL6IP5 0.87 0.010 22976 PAXIP1 0.87 0.009 60437 CDH26 0.87 0.004 23196 FAM120A 0.87 0.009 5983 RFC3 0.87 0.005 64431 ACTR6 0.87 0.005 55320 C14orf106 0.86 0.006 57213 C13orf1 0.86 0.006 51386 EIF3EIP 0.86 0.004 819 CAMLG 0.86 0.003 51499 TRIAP1 0.86 0.003 64897 C12orf43 0.86 0.003 10743 RAI1 0.86 0.005 5770 PTPN1 0.86 0.010 41 ACCN2 0.86 0.007 57547 ZNF624 0.86 0.004 79954 NOL10 0.86 0.004 23164 M-RIP 0.86 0.009 3148 HMGB2 0.86 0.003

84541 KBTBD8 0.86 0.003 57472 CNOT6 0.86 0.006 4809 NHP2L1 0.86 0.004 7071 KLF10 0.86 0.009 4976 OPA1 0.86 0.008 1964 EIF1AX 0.86 0.005 378 ARF4 0.86 0.006 10949 HNRNPA0 0.86 0.002 3707 ITPKB 0.86 0.010 10594 PRPF8 0.86 0.004 83452 RAB33B 0.86 0.004 219771 CCNY 0.86 0.004 3109 HLA-DMB 0.86 0.006 4670 HNRPM 0.86 0.008 5528 PPP2R5D 0.86 0.007 757 TMEM50B 0.86 0.005 153339 TMEM167 0.86 0.003 84925 DIRC2 0.86 0.004 25888 ZNF473 0.86 0.007 84250 ANKRD32 0.86 0.002 25809 TTLL1 0.86 0.005 95681 TSGA14 0.86 0.004 64968 MRPS6 0.86 0.006 5036 PA2G4 0.86 0.007 23116 KIAA0423 0.86 0.007 55161 TMEM33 0.86 0.003 114932 MRFAP1L1 0.86 0.003 23286 WWC1 0.86 0.004 10771 ZMYND11 0.86 0.003 10844 TUBGCP2 0.86 0.007 26515 FXC1 0.86 0.008 79022 TMEM106C 0.86 0.009 2186 BPTF 0.86 0.004 27229 76P 0.86 0.009 9391 CIAO1 0.86 0.003 7705 ZNF146 0.86 0.007 5431 POLR2B 0.86 0.002 129531 MITD1 0.86 0.002 374659 HDDC3 0.86 0.001 8165 AKAP1 0.86 0.002 2739 GLO1 0.86 0.007 84275 SLC25A33 0.86 0.006 7001 PRDX2 0.86 0.009 27067 STAU2 0.86 0.007 85403 EAF1 0.86 0.003 3065 HDAC1 0.86 0.005 6477 SIAH1 0.86 0.004 27241 BBS9 0.86 0.007 55857 C20orf19 0.86 0.006 27068 PPA2 0.86 0.005 10765 JARID1B 0.86 0.003 7486 WRN 0.86 0.009

122704 MRPL52 0.86 0.005 10228 STX6 0.86 0.008 4242 MFNG 0.86 0.004 3858 KRT10 0.86 0.007 5718 PSMD12 0.86 0.003 23326 USP22 0.86 0.004 6059 ABCE1 0.86 0.006 10898 CPSF4 0.86 0.007 90861 HN1L 0.86 0.004 25886 WDR51A 0.86 0.008 84656 N-PAC 0.86 0.009 6599 SMARCC1 0.86 0.008 10440 TIMM17A 0.86 0.007 159090 FAM122B 0.86 0.004 84262 PSMG3 0.86 0.009 50810 HDGFRP3 0.86 0.003 6117 RPA1 0.86 0.008 5716 PSMD10 0.86 0.009 201799 TMEM154 0.86 0.006 4189 DNAJB9 0.86 0.005 5681 PSKH1 0.86 0.005 5498 PPOX 0.86 0.007 8553 BHLHB2 0.85 0.006 9554 SEC22B 0.85 0.003 285989 ZNF789 0.85 0.006 84964 ALKBH6 0.85 0.007 64748 LPPR2 0.85 0.009 80110 ZNF614 0.85 0.008 10946 SF3A3 0.85 0.004 3064 HD 0.85 0.007 92106 OXNAD1 0.85 0.009 6400 SEL1L 0.85 0.009 7351 UCP2 0.85 0.005 9702 CEP57 0.85 0.003 84085 FBXO30 0.85 0.009 79157 MFSD11 0.85 0.006 6045 RNF2 0.85 0.009 9801 MRPL19 0.85 0.002 8761 PABPC4 0.85 0.002 84131 CEP78 0.85 0.003 57605 PITPNM2 0.85 0.007 254531 AGPAT7 0.85 0.009 9821 RB1CC1 0.85 0.003 3068 HDGF 0.85 0.006 23731 C9orf5 0.85 0.007 79724 ZNF768 0.85 0.009 55366 LGR4 0.85 0.006 6342 SCP2 0.85 0.006 51569 UFM1 0.85 0.003 51105 PHF20L1 0.85 0.003 54816 SUHW4 0.85 0.003 2124 EVI2B 0.85 0.005

23306 KIAA0286 0.85 0.009 1959 EGR2 0.85 0.007 119559 SFXN4 0.85 0.009 338661 PMP22CD 0.85 0.007 3015 H2AFZ 0.85 0.002 23588 KLHDC2 0.85 0.003 7621 ZNF70 0.85 0.009 7260 TSSC1 0.85 0.007 51203 NUSAP1 0.85 0.006 54800 KLHL24 0.85 0.008 130535 KCTD18 0.85 0.008 57150 C6orf162 0.85 0.007 64772 FLJ21865 0.85 0.009 1326 MAP3K8 0.85 0.006 55432 YOD1 0.85 0.007 121642 ALKBH2 0.85 0.009 6954 TCP11 0.85 0.009 51765 RP6-213H19.1 0.85 0.007 51275 C12orf47 0.85 0.008 10069 RWDD2B 0.85 0.007 22818 COPZ1 0.85 0.010 4973 OLR1 0.85 0.007 2178 FANCE 0.85 0.002 572 BAD 0.85 0.009 51108 METTL9 0.85 0.009 10621 POLR3F 0.85 0.006 23122 CLASP2 0.85 0.002 51194 IPO11 0.85 0.002 10640 EXOC5 0.85 0.005 114882 OSBPL8 0.85 0.007 643079 LOC643079 0.85 0.005 51324 SPG21 0.85 0.004 22934 RPIA 0.85 0.006 549 AUH 0.85 0.007 11329 STK38 0.85 0.008 9804 TOMM20 0.85 0.002 4092 SMAD7 0.85 0.009 4677 NARS 0.85 0.009 51382 ATP6V1D 0.85 0.006 3632 INPP5A 0.85 0.009 23252 OTUD3 0.85 0.010 26505 CNNM3 0.85 0.004 90075 ZNF30 0.85 0.008 672 BRCA1 0.85 0.002 64756 ATPAF1 0.85 0.006 54497 HEATR5B 0.85 0.003 501 ALDH7A1 0.85 0.002 9851 KIAA0753 0.85 0.007 5903 RANBP2 0.85 0.002 23078 RP11-125A7.3 0.85 0.007 83641 FAM107B 0.84 0.002 9016 SLC25A14 0.84 0.005

85313 PPIL4 0.84 0.005 4697 NDUFA4 0.84 0.005 55163 PNPO 0.84 0.009 81579 PLA2G12A 0.84 0.008 821 CANX 0.84 0.004 79603 LASS4 0.84 0.003 23094 SIPA1L3 0.84 0.004 57102 C12orf4 0.84 0.006 7247 TSN 0.84 0.007 50808 AK3 0.84 0.010 34 ACADM 0.84 0.005 374882 TMEM205 0.84 0.007 10476 ATP5H 0.84 0.010 2909 GRLF1 0.84 0.006 23517 SKIV2L2 0.84 0.003 84309 NUDT16L1 0.84 0.002 51780 JMJD1B 0.84 0.006 55825 PECR 0.84 0.009 55274 PHF10 0.84 0.002 153129 FLJ90709 0.84 0.007 23635 SSBP2 0.84 0.005 730202 LOC730202 0.84 0.009 64333 ARHGAP9 0.84 0.006 23321 TRIM2 0.84 0.009 23127 GLT25D2 0.84 0.007 80714 PBX4 0.84 0.008 29855 UBN1 0.84 0.006 10419 PRMT5 0.84 0.002 29087 THYN1 0.84 0.006 9662 CEP135 0.84 0.005 523 ATP6V1A 0.84 0.003 27292 DIMT1L 0.84 0.003 55090 MED9 0.84 0.003 597 BCL2A1 0.84 0.009 2123 EVI2A 0.84 0.006 4700 NDUFA6 0.84 0.009 83862 TMEM120A 0.84 0.006 54454 ATAD2B 0.84 0.004 50640 PNPLA8 0.84 0.009 10591 C6orf108 0.84 0.007 79600 TECT1 0.84 0.008 51522 TMEM14C 0.84 0.009 8727 CTNNAL1 0.84 0.009 144110 TMEM86A 0.84 0.009 196 AHR 0.84 0.008 7157 TP53 0.84 0.002 23051 ZHX3 0.84 0.010 26073 POLDIP2 0.84 0.007 57223 SMEK2 0.84 0.007 84154 BXDC1 0.84 0.008 7468 WHSC1 0.84 0.009 3187 HNRPH1 0.84 0.009

81037 CLPTM1L 0.84 0.003 25960 GPR124 0.84 0.006 2230 FDX1 0.84 0.009 51599 LSR 0.84 0.009 4706 NDUFAB1 0.84 0.002 23396 PIP5K1C 0.84 0.007 10947 AP3M2 0.84 0.007 4627 MYH9 0.84 0.008 130355 LOC130355 0.84 0.003 9863 MAGI2 0.84 0.007 10981 RAB32 0.84 0.009 29844 TFPT 0.84 0.004 54704 PPM2C 0.84 0.002 27131 SNX5 0.84 0.007 22954 TRIM32 0.84 0.003 55727 BTBD7 0.84 0.008 79745 CLIP4 0.84 0.003 3145 HMBS 0.84 0.004 117143 TADA1L 0.84 0.010 124790 HEXIM2 0.84 0.006 80218 NAT13 0.84 0.004 727726 LOC727726 0.84 0.003 2767 GNA11 0.84 0.006 51805 COQ3 0.84 0.008 64065 PERP 0.84 0.001 5573 PRKAR1A 0.84 0.003 54951 COMMD8 0.84 0.002 91433 RCCD1 0.84 0.009 58505 DC2 0.84 0.003 84529 C15orf41 0.84 0.004 79680 C22orf29 0.84 0.005 5303 PIN4 0.84 0.007 92675 DTD1 0.84 0.004 22838 RNF44 0.84 0.004 1763 DNA2L 0.84 0.006 3843 RANBP5 0.84 0.002 80150 ASRGL1 0.84 0.006 4832 NME3 0.84 0.003 7341 SUMO1 0.84 0.006 8209 C21orf33 0.84 0.005 8697 CDC23 0.84 0.002 79018 C17orf39 0.84 0.007 84928 FLJ14803 0.84 0.003 28986 MAGEH1 0.84 0.001 23014 FBXO21 0.84 0.009 55364 IMPACT 0.84 0.004 64170 CARD9 0.84 0.008 55184 C20orf12 0.84 0.005 54993 ZSCAN2 0.84 0.002 55119 PRPF38B 0.84 0.002 89978 ATPBD4 0.84 0.007 339804 LOC339804 0.84 0.005

83742 MARVELD1 0.84 0.004 25973 PARS2 0.83 0.003 3300 DNAJB2 0.83 0.006 4591 TRIM37 0.83 0.007 26058 TNRC15 0.83 0.009 57650 KIAA1524 0.83 0.002 151194 FAM119A 0.83 0.007 55156 ARMC1 0.83 0.003 54881 TEX10 0.83 0.001 93974 ATPIF1 0.83 0.007 10951 CBX1 0.83 0.007 10625 IVNS1ABP 0.83 0.003 23305 ACSL6 0.83 0.003 23038 WDTC1 0.83 0.009 924 CD7 0.83 0.010 9665 KIAA0430 0.83 0.006 26234 FBXL5 0.83 0.003 7064 THOP1 0.83 0.006 8611 PPAP2A 0.83 0.002 58508 MLL3 0.83 0.007 10026 PIGK 0.83 0.006 1536 CYBB 0.83 0.003 83759 RBM4B 0.83 0.003 7095 TLOC1 0.83 0.004 118487 CHCHD1 0.83 0.002 10040 TOM1L1 0.83 0.009 5889 RAD51C 0.83 0.003 5612 PRKRIR 0.83 0.003 91782 CHMP7 0.83 0.010 3516 RBPJ 0.83 0.007 50484 RRM2B 0.83 0.007 56271 BEXL1 0.83 0.006 440574 C1orf151 0.83 0.009 7728 ZNF175 0.83 0.006 10773 ZBTB6 0.83 0.007 64216 TFB2M 0.83 0.004 57136 C20orf3 0.83 0.007 5423 POLB 0.83 0.003 6867 TACC1 0.83 0.004 8939 FUBP3 0.83 0.006 142678 MIB2 0.83 0.008 23335 WDR7 0.83 0.002 139596 UPRT 0.83 0.002 114044 MCM3APAS 0.83 0.009 91647 ATPAF2 0.83 0.008 146712 B3GNTL1 0.83 0.009 55342 STRBP 0.83 0.006 8683 SFRS9 0.83 0.003 10938 EHD1 0.83 0.002 55328 C10orf59 0.83 0.008 54443 ANLN 0.83 0.010 84317 CCDC115 0.83 0.006

23548 TTC33 0.83 0.005 10849 CD3EAP 0.83 0.006 80223 RAB11FIP1 0.83 0.005 8886 DDX18 0.83 0.002 57799 RAB40C 0.83 0.007 9646 CTR9 0.83 0.001 85457 KIAA1737 0.83 0.010 11275 KLHL2 0.83 0.007 23102 TBC1D2B 0.83 0.002 54107 POLE3 0.83 0.007 120892 LRRK2 0.83 0.004 29127 RACGAP1 0.83 0.003 23287 AGTPBP1 0.83 0.007 79065 ATG9A 0.83 0.009 53373 TPCN1 0.83 0.009 116064 LRRC58 0.83 0.009 23412 COMMD3 0.83 0.003 83464 APH1B 0.83 0.009 10769 PLK2 0.83 0.007 326625 MMAB 0.83 0.004 84188 MLSTD2 0.83 0.002 64792 RABL5 0.83 0.006 10263 CDK2AP2 0.83 0.002 50615 IL21R 0.83 0.003 56916 SMARCAD1 0.83 0.002 57724 KIAA1632 0.83 0.002 285521 COX18 0.83 0.003 11160 ERLIN2 0.83 0.002 162239 ZFP1 0.83 0.006 29929 ALG6 0.83 0.004 5782 PTPN12 0.83 0.008 7804 LRP8 0.83 0.009 57531 HACE1 0.83 0.008 51528 C14orf100 0.83 0.004 64981 MRPL34 0.83 0.009 10526 IPO8 0.83 0.003 55471 C2orf56 0.83 0.002 9364 RAB28 0.83 0.002 51133 KCTD3 0.82 0.009 1947 EFNB1 0.82 0.009 9867 PJA2 0.82 0.003 56915 EXOSC5 0.82 0.007 25800 SLC39A6 0.82 0.006 4782 NFIC 0.82 0.006 23074 KIAA0701 0.82 0.008 6981 TRGV7 0.82 0.006 54014 BRWD1 0.82 0.002 90462 ZNF605 0.82 0.009 8435 SOAT2 0.82 0.004 8520 HAT1 0.82 0.004 10007 GNPDA1 0.82 0.010 5162 PDHB 0.82 0.002

6048 RNF5 0.82 0.007 79017 C7orf24 0.82 0.006 30815 ST6GALNAC6 0.82 0.006 9692 KIAA0391 0.82 0.009 4232 MEST 0.82 0.007 11124 FAF1 0.82 0.007 54700 RRN3 0.82 0.001 51144 HSD17B12 0.82 0.007 3459 IFNGR1 0.82 0.005 1945 EFNA4 0.82 0.007 8027 STAM 0.82 0.003 80194 TMEM134 0.82 0.003 64764 CREB3L2 0.82 0.002 9927 MFN2 0.82 0.003 85476 GFM1 0.82 0.006 22924 MAPRE3 0.82 0.009 123263 MTFMT 0.82 0.009 10128 LRPPRC 0.82 0.001 647087 PL-5283 0.82 0.004 144108 SPTY2D1 0.82 0.003 23594 ORC6L 0.82 0.005 345757 TMEM157 0.82 0.006 56900 TMEM167B 0.82 0.003 55256 ADI1 0.82 0.006 253558 LYCAT 0.82 0.006 57180 ACTR3B 0.82 0.004 4698 NDUFA5 0.82 0.009 84230 LRRC8C 0.82 0.006 93 ACVR2B 0.82 0.006 7381 UQCRB 0.82 0.004 56647 BCCIP 0.82 0.003 400 ARL1 0.82 0.003 51809 GALNT7 0.82 0.001 7390 UROS 0.82 0.005 493911 PHOSPHO2 0.82 0.010 55635 DEPDC1 0.82 0.010 85365 ALG2 0.82 0.001 112942 CCDC104 0.82 0.009 54982 CLN6 0.82 0.005 9649 RALGPS1 0.82 0.009 23479 ISCU 0.82 0.002 23353 UNC84A 0.82 0.002 260429 PRSS33 0.82 0.007 58493 C9orf80 0.82 0.007 2184 FAH 0.82 0.009 3925 STMN1 0.82 0.005 727742 LOC727742 0.82 0.003 146547 PRSS36 0.82 0.006 10175 CNIH 0.82 0.006 51673 TPPP3 0.82 0.007 119710 C11orf74 0.82 0.003 6391 SDHC 0.82 0.006

49854 ZNF295 0.82 0.006 26123 TCTN3 0.82 0.001 56971 CEACAM19 0.82 0.003 1894 ECT2 0.82 0.009 55334 SLC39A9 0.82 0.001 8732 RNGTT 0.82 0.005 23384 SPECC1L 0.82 0.003 7187 TRAF3 0.82 0.005 4860 NP 0.82 0.007 56994 CHPT1 0.82 0.003 81490 PTDSS2 0.82 0.007 7155 TOP2B 0.82 0.003 55717 BRWD2 0.82 0.007 5591 PRKDC 0.82 0.008 152559 PAQR3 0.82 0.003 27346 TMEM97 0.82 0.006 80298 MTERFD3 0.82 0.006 84836 ABHD14B 0.82 0.003 440498 LOC440498 0.82 0.002 149076 FLJ25476 0.81 0.004 81853 TMEM14B 0.81 0.004 54069 C21orf45 0.81 0.010 6309 SC5DL 0.81 0.006 2068 ERCC2 0.81 0.007 84708 LNX1 0.81 0.006 11130 ZWINT 0.81 0.003 79650 C16orf57 0.81 0.006 81567 TXNDC5 0.81 0.006 55284 UBE2W 0.81 0.002 516 ATP5G1 0.81 0.007 60312 AFAP1 0.81 0.002 1123 CHN1 0.81 0.004 378464 MORN2 0.81 0.010 4215 MAP3K3 0.81 0.003 5435 POLR2F 0.81 0.003 142940 TRUB1 0.81 0.002 23463 ICMT 0.81 0.007 79675 FASTKD1 0.81 0.009 84167 C19orf44 0.81 0.005 55081 IFT57 0.81 0.007 54923 LIME1 0.81 0.009 131566 DCBLD2 0.81 0.003 55132 LARP2 0.81 0.006 80790 CMIP 0.81 0.007 92345 LOC92345 0.81 0.008 341 APOC1 0.81 0.003 8445 DYRK2 0.81 0.003 6787 NEK4 0.81 0.007 649446 FLJ35776 0.81 0.002 11325 DDX42 0.81 0.002 79573 TTC13 0.81 0.000 81562 LMAN2L 0.81 0.007

131474 CHCHD4 0.81 0.002 1454 CSNK1E 0.81 0.003 79921 TCEAL4 0.81 0.005 23270 TSPYL4 0.81 0.003 10388 SYCP2 0.81 0.004 57003 CCDC47 0.81 0.002 221914 GPC2 0.81 0.003 84331 C16orf14 0.81 0.010 10318 TNIP1 0.81 0.004 157285 DKFZp761P0423 0.81 0.005 338758 LOC338758 0.81 0.006 26586 CKAP2 0.81 0.003 51076 CUTC 0.81 0.004 55041 PLEKHB2 0.81 0.007 6636 SNRPF 0.81 0.008 6197 RPS6KA3 0.81 0.002 3298 HSF2 0.81 0.003 11022 TDRKH 0.81 0.007 4065 LY75 0.81 0.008 29789 OLA1 0.81 0.009 94241 TP53INP1 0.81 0.003 51205 ACP6 0.81 0.005 83716 CRISPLD2 0.81 0.008 11231 SEC63 0.81 0.003 161779 PGBD4 0.81 0.009 353274 ZNF445 0.81 0.000 90843 TCEAL8 0.81 0.001 51573 MIR16 0.81 0.006 55655 NLRP2 0.81 0.002 54955 C1orf109 0.81 0.003 55534 MAML3 0.81 0.010 93081 C13orf27 0.81 0.005 56919 DHX33 0.81 0.002 64407 RGS18 0.81 0.007 400446 LOC400446 0.81 0.004 8578 SCARF1 0.81 0.006 58526 MID1IP1 0.81 0.004 83989 C5orf21 0.81 0.005 285440 CYP4V2 0.81 0.009 129401 NUP35 0.81 0.002 9021 SOCS3 0.81 0.004 126375 ZNF792 0.81 0.008 10926 DBF4 0.81 0.006 63979 FIGNL1 0.81 0.004 6659 SOX4 0.81 0.007 10159 ATP6AP2 0.81 0.002 29902 C12orf24 0.81 0.006 56261 RP5-1022P6.2 0.81 0.004 4867 NPHP1 0.81 0.009 84105 PCBD2 0.81 0.009 6573 SLC19A1 0.81 0.002 286151 FBXO43 0.81 0.006

91147 TMEM67 0.81 0.005 64860 ARMCX5 0.81 0.003 5538 PPT1 0.81 0.003 7027 TFDP1 0.81 0.006 23357 ANGEL1 0.81 0.005 5723 PSPH 0.81 0.009 55723 ASF1B 0.81 0.010 1362 CPD 0.80 0.003 10554 AGPAT1 0.80 0.006 10472 ZNF238 0.80 0.000 8574 AKR7A2 0.80 0.002 65059 RAPH1 0.80 0.006 145173 B3GALTL 0.80 0.003 10402 ST3GAL6 0.80 0.005 96459 FNIP1 0.80 0.001 55760 DHX32 0.80 0.004 113655 MFSD3 0.80 0.002 2589 GALNT1 0.80 0.003 1353 COX11 0.80 0.003 5264 PHYH 0.80 0.007 440957 LOC440957 0.80 0.008 8501 SLC43A1 0.80 0.002 10206 TRIM13 0.80 0.002 51744 CD244 0.80 0.006 8819 SAP30 0.80 0.002 79731 NARS2 0.80 0.004 6733 SRPK2 0.80 0.005 147965 FAM98C 0.80 0.009 8195 MKKS 0.80 0.007 5867 RAB4A 0.80 0.007 56890 MDM1 0.80 0.002 23467 NPTXR 0.80 0.009 178 AGL 0.80 0.006 29969 MDFIC 0.80 0.002 79258 MMEL1 0.80 0.007 9879 DDX46 0.80 0.002 440275 EIF2AK4 0.80 0.001 32 ACACB 0.80 0.007 116151 C20orf108 0.80 0.003 143879 KBTBD3 0.80 0.005 79850 FAM57A 0.80 0.006 51161 C3orf18 0.80 0.005 140685 ZBTB46 0.80 0.009 51031 GLOD4 0.80 0.006 11127 KIF3A 0.80 0.002 79673 ZNF329 0.80 0.003 80183 C13orf18 0.80 0.006 51084 CRYL1 0.80 0.010 57522 SRGAP1 0.80 0.007 56998 CTNNBIP1 0.80 0.001 115024 NT5C3L 0.80 0.002 58490 C20orf77 0.80 0.002

112487 C14orf126 0.80 0.001 5033 P4HA1 0.80 0.000 51109 RDH11 0.80 0.006 3295 HSD17B4 0.80 0.003 2395 FXN 0.80 0.003 163227 ZNF100 0.80 0.009 286826 LIN9 0.80 0.004 83719 YPEL3 0.80 0.002 219854 LOC219854 0.80 0.003 2781 GNAZ 0.80 0.003 5584 PRKCI 0.80 0.002 200734 SPRED2 0.80 0.006 79616 CCNJL 0.80 0.006 57479 PRR12 0.80 0.003 1869 E2F1 0.80 0.007 259282 FAM44A 0.80 0.002 9604 RNF14 0.80 0.007 2157 F8 0.80 0.007 9562 MINPP1 0.80 0.003 1069 CETN2 0.80 0.008 1642 DDB1 0.80 0.002 9197 SLC33A1 0.80 0.005 56180 MOSPD1 0.80 0.009 93058 COQ10A 0.80 0.002 79646 PANK3 0.80 0.005 63917 GALNT11 0.80 0.007 5176 SERPINF1 0.80 0.006 84078 KBTBD7 0.80 0.003 91582 RPS19BP1 0.80 0.009 25874 BRP44 0.80 0.003 79828 METTL8 0.80 0.006 80818 ZNF436 0.80 0.005 4884 NPTX1 0.80 0.009 6103 RPGR 0.80 0.007 84986 ARHGAP19 0.80 0.006 134728 IRAK1BP1 0.80 0.003 3156 HMGCR 0.80 0.002 1628 DBP 0.80 0.004 57666 KIAA1545 0.80 0.007 124152 IQCK 0.80 0.007 134553 C5orf24 0.80 0.000 3033 HADH 0.80 0.003 11333 PDAP1 0.80 0.010 84634 KISS1R 0.80 0.007 23658 LSM5 0.80 0.002 4090 SMAD5 0.80 0.006 10099 TSPAN3 0.80 0.009 57335 ZNF286A 0.80 0.010 528 ATP6V1C1 0.80 0.007 1 A1BG 0.80 0.008 8681 PLA2G4B 0.80 0.002 85464 SSH2 0.80 0.003

57380 MRS2L 0.80 0.003 9452 ITM2A 0.79 0.006 254863 C17orf61 0.79 0.010 644353 LOC644353 0.79 0.002 3454 IFNAR1 0.79 0.005 51088 KLHL5 0.79 0.002 729230 CCR2 0.79 0.002 8402 SLC25A11 0.79 0.003 373 TRIM23 0.79 0.004 945 CD33 0.79 0.004 4719 NDUFS1 0.79 0.007 51363 GALNAC4S-6ST 0.79 0.006 256356 GK5 0.79 0.005 10666 CD226 0.79 0.008 283464 GLT8D3 0.79 0.001 79622 C16orf33 0.79 0.005 401548 SNX30 0.79 0.005 224 ALDH3A2 0.79 0.005 2218 FCMD 0.79 0.009 27440 CECR5 0.79 0.002 400566 LOC400566 0.79 0.006 127943 FCRLB 0.79 0.007 54885 TBC1D8B 0.79 0.001 8518 IKBKAP 0.79 0.003 4122 MAN2A2 0.79 0.006 8302 KLRC4 0.79 0.007 54495 TXNDC10 0.79 0.002 51474 LIMA1 0.79 0.009 1293 COL6A3 0.79 0.010 267002 PGBD2 0.79 0.009 84908 FAM136A 0.79 0.003 9466 IL27RA 0.79 0.006 1021 CDK6 0.79 0.006 10196 PRMT3 0.79 0.003 129138 ANKRD54 0.79 0.006 7358 UGDH 0.79 0.006 219749 ZNF25 0.79 0.001 8270 LAGE3 0.79 0.003 22994 AZI1 0.79 0.004 23299 BICD2 0.79 0.002 9241 NOG 0.79 0.002 1182 CLCN3 0.79 0.006 3687 ITGAX 0.79 0.009 90025 C6orf157 0.79 0.008 27349 MCAT 0.79 0.005 327657 SERPINA9 0.79 0.002 9654 TTLL4 0.79 0.007 284612 SYPL2 0.79 0.006 55902 ACSS2 0.79 0.006 401209 FLJ44796 0.79 0.003 65260 C1orf163 0.79 0.002 1955 MEGF9 0.79 0.007

84247 LDOC1L 0.79 0.004 55851 PSENEN 0.79 0.006 167691 LCA5 0.79 0.006 10210 TOPORS 0.79 0.003 3176 HNMT 0.79 0.002 10257 ABCC4 0.79 0.002 84058 WDR54 0.78 0.006 55592 GOLGA2L1 0.78 0.003 2026 ENO2 0.78 0.002 84747 UNC119B 0.78 0.002 144348 ZNF664 0.78 0.002 1108 CHD4 0.78 0.005 130507 ZNF650 0.78 0.002 201161 PRR6 0.78 0.000 91373 UAP1L1 0.78 0.006 7762 ZNF215 0.78 0.009 23135 JMJD3 0.78 0.005 148304 C1orf74 0.78 0.006 10279 PRSS16 0.78 0.010 360 AQP3 0.78 0.007 79738 BBS10 0.78 0.001 23590 PDSS1 0.78 0.010 11112 HIBADH 0.78 0.005 55556 ENOSF1 0.78 0.002 401431 LOC401431 0.78 0.008 31 ACACA 0.78 0.003 253635 CCDC75 0.78 0.001 9655 SOCS5 0.78 0.003 140883 SUHW2 0.78 0.003 10079 ATP9A 0.78 0.001 57211 GPR126 0.78 0.009 51706 CYB5R1 0.78 0.004 8722 CTSF 0.78 0.005 84327 ZBED3 0.78 0.002 57728 WDR19 0.78 0.007 5465 PPARA 0.78 0.006 10732 TCFL5 0.78 0.002 59338 PLEKHA1 0.78 0.003 7840 ALMS1 0.78 0.006 83450 LRRC48 0.78 0.008 254394 MCM9 0.78 0.003 818 CAMK2G 0.78 0.003 10929 SFRS2B 0.78 0.003 4330 MN1 0.78 0.003 79644 SRD5A2L 0.78 0.006 151011 39701 0.78 0.006 23409 SIRT4 0.78 0.001 25777 UNC84B 0.78 0.002 349565 NMNAT3 0.78 0.004 84947 SERAC1 0.78 0.005 3795 KHK 0.78 0.007 6675 UAP1 0.78 0.003

55071 C9orf40 0.78 0.001 64781 CERK 0.78 0.003 200765 TIGD1 0.78 0.009 27336 HTATSF1 0.78 0.000 7480 WNT10B 0.78 0.009 400924 LOC400924 0.78 0.002 51192 CKLF 0.78 0.004 57189 KIAA1147 0.78 0.003 1389 CREBL2 0.78 0.002 4815 NINJ2 0.78 0.009 57496 MKL2 0.78 0.003 8455 ATRN 0.78 0.003 8936 WASF1 0.78 0.009 28962 OSTM1 0.78 0.004 9818 NUPL1 0.78 0.010 26225 ARL5A 0.78 0.003 9953 HS3ST3B1 0.78 0.007 113802 C1orf59 0.78 0.002 10560 SLC19A2 0.78 0.006 8671 SLC4A4 0.78 0.002 25829 TMEM184B 0.78 0.005 26031 OSBPL3 0.78 0.006 5051 PAFAH2 0.78 0.008 55314 TMEM144 0.78 0.001 8111 GPR68 0.78 0.002 729013 LOC729013 0.78 0.003 9620 CELSR1 0.77 0.003 1043 CD52 0.77 0.002 87 ACTN1 0.77 0.009 4728 NDUFS8 0.77 0.006 55722 CEP72 0.77 0.007 129790 C7orf13 0.77 0.008 55617 TASP1 0.77 0.003 2870 GRK6 0.77 0.007 119032 C10orf32 0.77 0.001 266655 FLJ35348 0.77 0.006 9920 KBTBD11 0.77 0.002 7408 VASP 0.77 0.008 286319 TUSC1 0.77 0.003 6364 CCL20 0.77 0.005 153364 LOC153364 0.77 0.002 22881 ANKRD6 0.77 0.005 23022 PALLD 0.77 0.009 85453 TSPYL5 0.77 0.003 6566 SLC16A1 0.77 0.006 26043 UBXD7 0.77 0.002 55276 PGM2 0.77 0.001 94274 PPP1R14A 0.77 0.003 57569 ARHGAP20 0.77 0.004 54849 DEF8 0.77 0.009 54431 DNAJC10 0.77 0.004 23060 ZNF609 0.77 0.006

54914 KIAA1797 0.77 0.003 157506 RDH10 0.77 0.003 2628 GATM 0.77 0.003 5863 RGL2 0.77 0.003 79956 ERMP1 0.77 0.007 5825 ABCD3 0.77 0.003 84056 KATNAL1 0.77 0.009 23531 MMD 0.77 0.008 6653 SORL1 0.77 0.006 5781 PTPN11 0.77 0.003 3205 HOXA9 0.77 0.009 5361 PLXNA1 0.77 0.003 7248 TSC1 0.77 0.002 5830 PEX5 0.77 0.002 81928 CABLES2 0.77 0.006 57406 ABHD6 0.77 0.006 3703 STT3A 0.77 0.004 64080 RBKS 0.77 0.001 79752 ZFAND1 0.77 0.000 440465 FLJ90757 0.77 0.001 65996 MGC2752 0.77 0.004 112611 RWDD2A 0.77 0.007 57181 SLC39A10 0.77 0.000 129303 TMEM150 0.77 0.008 79624 C6orf211 0.77 0.002 23639 LRRC6 0.77 0.009 92610 TIFA 0.77 0.002 25778 RIPK5 0.77 0.002 374986 FAM73A 0.77 0.003 55102 ATG2B 0.77 0.003 81831 NETO2 0.77 0.001 55002 TMCO3 0.77 0.009 171546 C14orf147 0.77 0.004 5530 PPP3CA 0.77 0.004 57539 WDR35 0.77 0.003 57563 KLHL8 0.77 0.006 80263 TRIM45 0.77 0.008 57571 KIAA1394 0.77 0.003 1901 EDG1 0.77 0.003 64924 SLC30A5 0.77 0.002 63941 APBA2BP 0.77 0.006 4942 OAT 0.77 0.001 220 ALDH1A3 0.77 0.009 148823 C1orf150 0.76 0.005 23262 HISPPD1 0.76 0.006 64858 DCLRE1B 0.76 0.003 55015 PRPF39 0.76 0.006 5281 PIGF 0.76 0.002 84108 PCGF6 0.76 0.003 57519 STARD9 0.76 0.006 9778 KIAA0232 0.76 0.002 23129 PLXND1 0.76 0.008

9451 EIF2AK3 0.76 0.001 395 ARHGAP6 0.76 0.009 90102 PHLDB2 0.76 0.001 92691 TMEM169 0.76 0.002 26289 AK5 0.76 0.004 54965 PIGX 0.76 0.004 90835 LOC90835 0.76 0.007 8773 SNAP23 0.76 0.005 54942 C9orf6 0.76 0.002 353189 SLCO4C1 0.76 0.010 9645 MICAL2 0.76 0.009 23604 DAPK2 0.76 0.002 2242 FES 0.76 0.009 64172 OSGEPL1 0.76 0.004 182 JAG1 0.76 0.004 10638 SPHAR 0.76 0.007 23023 TMCC1 0.76 0.009 130074 LOC130074 0.76 0.003 84657 C3orf42 0.76 0.001 285962 FLJ40852 0.76 0.007 10982 MAPRE2 0.76 0.002 124221 MGC52282 0.76 0.002 51537 MTP18 0.76 0.002 5287 PIK3C2B 0.76 0.007 28984 C13orf15 0.76 0.003 91419 XRCC6BP1 0.76 0.008 10277 UBE4B 0.76 0.009 548645 bA16L21.2.1 0.76 0.002 283284 IGSF22 0.76 0.003 284018 C17orf58 0.76 0.006 58528 RRAGD 0.76 0.006 29901 SAC3D1 0.76 0.005 148646 C1orf188 0.76 0.005 23401 FRAT2 0.76 0.002 1130 LYST 0.76 0.006 80235 PIGZ 0.76 0.005 10382 TUBB4 0.76 0.003 28978 TMEM14A 0.76 0.002 6286 S100P 0.76 0.002 6013 RLN1 0.75 0.003 64105 CENPK 0.75 0.007 5829 PXN 0.75 0.003 5360 PLTP 0.75 0.007 440122 hCG_1646157 0.75 0.001 388381 LOC388381 0.75 0.005 27284 SULT1B1 0.75 0.010 127700 C1orf102 0.75 0.007 6515 SLC2A3 0.75 0.001 10380 BPNT1 0.75 0.003 55706 TMEM48 0.75 0.003 149420 PDIK1L 0.75 0.001 2059 EPS8 0.75 0.005

283537 SLC46A3 0.75 0.003 51540 SCLY 0.75 0.003 114792 KLHL32 0.75 0.009 85478 CCDC65 0.75 0.007 83594 NUDT12 0.75 0.009 30845 EHD3 0.75 0.007 167681 PRSS35 0.75 0.003 54675 CRLS1 0.75 0.000 124637 CYB5D1 0.75 0.002 7813 EVI5 0.75 0.006 64397 ZFP106 0.75 0.006 284023 LOC284023 0.75 0.001 53822 FXYD7 0.75 0.001 26191 PTPN22 0.75 0.001 23171 GPD1L 0.75 0.001 137392 FAM92A1 0.75 0.009 7772 ZNF229 0.75 0.002 6519 SLC3A1 0.75 0.006 91039 DPP9 0.75 0.004 11128 POLR3A 0.75 0.002 7049 TGFBR3 0.75 0.003 7771 ZNF228 0.75 0.010 64411 CENTD3 0.75 0.003 1070 CETN3 0.75 0.000 6272 SORT1 0.75 0.010 83657 DYNLRB2 0.75 0.009 154467 C6orf129 0.75 0.003 84658 EMR3 0.75 0.006 267 AMFR 0.75 0.007 140462 ASB9 0.75 0.007 667 DST 0.75 0.007 3556 IL1RAP 0.75 0.009 9306 SOCS6 0.75 0.007 8100 IFT88 0.75 0.005 11020 RABL4 0.75 0.003 51665 ASB1 0.75 0.003 439921 MXRA7 0.74 0.002 147947 ZNF542 0.74 0.004 3309 HSPA5 0.74 0.002 29090 C18orf55 0.74 0.003 2353 FOS 0.74 0.009 121457 IKIP 0.74 0.003 1840 DTX1 0.74 0.004 6450 SH3BGR 0.74 0.007 10804 GJB6 0.74 0.002 97 ACYP1 0.74 0.002 9770 RASSF2 0.74 0.002 5604 MAP2K1 0.74 0.003 81888 HYI 0.74 0.002 9859 CEP170 0.74 0.002 8754 ADAM9 0.74 0.006 89890 KBTBD6 0.74 0.001

93589 CACNA2D4 0.74 0.007 79899 FLJ14213 0.74 0.006 9338 TCEAL1 0.74 0.001 283876 FLJ39639 0.74 0.000 272 AMPD3 0.74 0.010 79064 MGC3196 0.74 0.003 79172 CENPO 0.74 0.007 84002 B3GNT5 0.74 0.006 8660 IRS2 0.74 0.002 26579 MYEOV 0.74 0.009 8863 PER3 0.74 0.008 1266 CNN3 0.74 0.003 169981 SPIN3 0.74 0.001 51171 HSD17B14 0.74 0.005 10189 THOC4 0.74 0.002 121506 ERP27 0.74 0.003 55852 TEX2 0.74 0.006 54997 TESC 0.74 0.003 5569 PKIA 0.74 0.004 145389 SLC38A6 0.74 0.009 7046 TGFBR1 0.74 0.004 54805 CNNM2 0.74 0.002 7168 TPM1 0.74 0.005 1371 CPOX 0.74 0.001 9256 BZRAP1 0.74 0.004 57096 RPGRIP1 0.74 0.007 9706 ULK2 0.74 0.004 80315 CPEB4 0.73 0.003 10418 SPON1 0.73 0.002 199857 ALG14 0.73 0.005 6596 HLTF 0.73 0.002 79447 C16orf53 0.73 0.005 7442 TRPV1 0.73 0.003 1465 CSRP1 0.73 0.005 342897 NCCRP1 0.73 0.005 8491 MAP4K3 0.73 0.001 1601 DAB2 0.73 0.006 55752 39702 0.73 0.003 219833 C11orf45 0.73 0.009 27152 INTU 0.73 0.002 8707 B3GALT2 0.73 0.006 4692 NDN 0.73 0.006 4257 MGST1 0.73 0.003 9736 USP34 0.73 0.006 36 ACADSB 0.73 0.002 221692 PHACTR1 0.73 0.002 115761 ARL11 0.73 0.003 9832 JAKMIP2 0.73 0.008 90624 LYRM7 0.73 0.003 170371 C10orf128 0.73 0.002 387923 C13orf21 0.73 0.007 55789 DEPDC1B 0.73 0.003

444 ASPH 0.73 0.009 64837 KLC2 0.73 0.007 9647 PPM1F 0.73 0.002 55151 TMEM38B 0.73 0.003 1718 DHCR24 0.73 0.006 152185 CCDC52 0.73 0.007 7023 TFAP4 0.73 0.006 2268 FGR 0.73 0.007 1593 CYP27A1 0.73 0.004 2043 EPHA4 0.73 0.006 387882 OCC-1 0.73 0.003 6678 SPARC 0.73 0.006 3642 INSM1 0.72 0.009 7485 WRB 0.72 0.009 55759 WDR12 0.72 0.000 7466 WFS1 0.72 0.003 90378 SAMD1 0.72 0.003 58484 NLRC4 0.72 0.005 58473 PLEKHB1 0.72 0.009 928 CD9 0.72 0.003 55704 CCDC88A 0.72 0.008 23012 STK38L 0.72 0.001 131583 FAM43A 0.72 0.001 6558 SLC12A2 0.72 0.002 84969 TOX2 0.72 0.010 115548 FCHO2 0.72 0.008 6622 SNCA 0.72 0.009 65018 PINK1 0.72 0.003 79939 SLC35E1 0.72 0.003 155066 ATP6V0E2 0.72 0.003 109 ADCY3 0.72 0.005 29785 CYP2S1 0.72 0.007 50862 RNF141 0.72 0.001 84924 ZNF566 0.72 0.006 2768 GNA12 0.72 0.009 5911 RAP2A 0.72 0.002 18 ABAT 0.72 0.002 7414 VCL 0.72 0.004 374408 MGC12965 0.72 0.001 134957 STXBP5 0.72 0.006 55172 C14orf104 0.72 0.003 283663 LOC283663 0.72 0.005 84293 C10orf58 0.72 0.004 8277 TKTL1 0.71 0.007 64921 CASD1 0.71 0.000 57678 GPAM 0.71 0.002 8038 ADAM12 0.71 0.005 54558 SPATA6 0.71 0.002 1050 CEBPA 0.71 0.002 6019 RLN2 0.71 0.001 23473 CAPN7 0.71 0.001 6713 SQLE 0.71 0.008

3815 KIT 0.71 0.004 202243 CCDC125 0.71 0.003 7504 XK 0.71 0.006 3892 KRT86 0.71 0.003 51228 GLTP 0.71 0.002 1407 CRY1 0.71 0.002 54910 SEMA4C 0.71 0.006 348751 LOC348751 0.71 0.006 84649 DGAT2 0.71 0.001 57161 PELI2 0.71 0.002 7267 TTC3 0.71 0.003 85414 SLC45A3 0.71 0.004 51385 ZNF589 0.71 0.003 1836 SLC26A2 0.71 0.003 50488 MINK1 0.71 0.003 1855 DVL1 0.71 0.002 23313 C22orf9 0.71 0.003 2206 MS4A2 0.71 0.004 440829 C22:CTA-250D10.9 0.71 0.003 90874 ZNF697 0.71 0.009 92104 TTC30A 0.71 0.009 23243 ANKRD28 0.71 0.002 64854 USP46 0.71 0.002 27065 D4S234E 0.71 0.002 6790 AURKA 0.70 0.003 9069 CLDN12 0.70 0.000 9650 MTFR1 0.70 0.003 79829 NAT11 0.70 0.003 26258 PLDN 0.70 0.002 151473 SLC16A14 0.70 0.000 6283 S100A12 0.70 0.002 55213 RCBTB1 0.70 0.002 4674 NAP1L2 0.70 0.001 5328 PLAU 0.70 0.004 730112 LOC730112 0.70 0.005 23232 TBC1D12 0.70 0.003 1183 CLCN4 0.70 0.002 54841 BIVM 0.70 0.007 79699 ZYG11B 0.70 0.003 9581 PREPL 0.70 0.001 57001 ACN9 0.70 0.002 80823 BHLHB9 0.70 0.009 3684 ITGAM 0.70 0.002 5566 PRKACA 0.70 0.002 284367 SIGLECP3 0.70 0.006 64757 MOSC1 0.70 0.006 3553 IL1B 0.70 0.009 222658 KCTD20 0.70 0.003 24149 ZNF318 0.70 0.001 2 A2M 0.70 0.002 23130 ATG2A 0.70 0.002 145482 ZADH1 0.70 0.003

64110 MAGEF1 0.70 0.002 9120 SLC16A6 0.69 0.004 10200 MPHOSPH6 0.69 0.002 10253 SPRY2 0.69 0.007 285550 LOC285550 0.69 0.000 246330 PELI3 0.69 0.004 90736 FAM104B 0.69 0.001 1954 MEGF8 0.69 0.003 285154 C2orf58 0.69 0.004 23648 SSBP3 0.69 0.000 490 ATP2B1 0.69 0.001 7220 TRPC1 0.69 0.003 11098 PRSS23 0.69 0.003 102 ADAM10 0.69 0.002 9936 CD302 0.69 0.002 1952 CELSR2 0.69 0.001 286495 TTC3L 0.69 0.004 54899 PXK 0.69 0.003 340547 VSIG1 0.69 0.002 10129 FRY 0.69 0.006 5330 PLCB2 0.69 0.002 170591 S100Z 0.69 0.007 8364 HIST1H4C 0.69 0.003 3371 TNC 0.69 0.010 25911 RP11-529I10.4 0.69 0.002 84279 C2orf7 0.69 0.002 53354 PANK1 0.68 0.007 23768 FLRT2 0.68 0.007 80303 EFHD1 0.68 0.002 57595 PDZD4 0.68 0.001 399664 MEX3D 0.68 0.001 10090 UST 0.68 0.004 26160 IFT172 0.68 0.004 114134 SLC2A13 0.68 0.002 7464 CORO2A 0.68 0.003 255394 TCP11L2 0.68 0.007 55728 N4BP2 0.68 0.003 57679 ALS2 0.68 0.003 10224 ZNF443 0.68 0.006 22927 HABP4 0.68 0.000 5217 PFN2 0.68 0.006 83449 PMFBP1 0.68 0.009 7371 UCK2 0.68 0.003 57533 TBC1D14 0.68 0.002 728997 LOC728997 0.68 0.007 10741 RBBP9 0.68 0.001 6920 TCEA3 0.68 0.003 57683 ZDBF2 0.68 0.007 284611 FAM102B 0.68 0.001 586 BCAT1 0.67 0.003 595 CCND1 0.67 0.001 84288 EFCAB2 0.67 0.002

57473 ZNF512B 0.67 0.001 932 MS4A3 0.67 0.009 4048 LTA4H 0.67 0.002 857 CAV1 0.67 0.003 23150 FRMD4B 0.67 0.001 9990 SLC12A6 0.67 0.002 3248 HPGD 0.67 0.002 201562 PTPLB 0.67 0.002 59277 NTN4 0.67 0.001 5742 PTGS1 0.67 0.002 5467 PPARD 0.67 0.002 286205 C9orf126 0.67 0.002 137835 TMEM71 0.67 0.002 9398 IGSF2 0.67 0.003 10150 MBNL2 0.67 0.001 9497 SLC4A7 0.67 0.001 55686 MREG 0.67 0.003 7039 TGFA 0.67 0.002 9653 HS2ST1 0.67 0.002 23158 TBC1D9 0.67 0.002 51626 DYNC2LI1 0.67 0.002 53346 TM6SF1 0.67 0.003 139886 SPIN4 0.67 0.005 23555 TSPAN15 0.67 0.008 55790 ChGn 0.67 0.004 3693 ITGB5 0.67 0.009 23678 SGK3 0.67 0.003 978 CDA 0.67 0.002 6785 ELOVL4 0.66 0.001 23413 FREQ 0.66 0.006 130951 LOC130951 0.66 0.004 51738 GHRL 0.66 0.002 8853 DDEF2 0.66 0.001 79718 TBL1XR1 0.66 0.000 125170 SMCR7 0.66 0.001 7422 VEGFA 0.66 0.002 51 ACOX1 0.66 0.003 23261 CAMTA1 0.66 0.007 91283 C9orf30 0.66 0.009 5270 SERPINE2 0.66 0.006 2941 GSTA4 0.66 0.003 84417 C2orf40 0.66 0.006 114928 GPRASP2 0.66 0.003 54585 LZTFL1 0.66 0.001 3783 KCNN4 0.66 0.002 2811 GP1BA 0.66 0.006 80854 SETD7 0.66 0.000 4051 CYP4F3 0.66 0.001 3554 IL1R1 0.66 0.003 8836 GGH 0.66 0.003 26523 EIF2C1 0.66 0.001 23322 RPGRIP1L 0.66 0.003

10740 RFPL1S 0.66 0.002 5743 PTGS2 0.66 0.005 29904 EEF2K 0.66 0.002 8577 TMEFF1 0.65 0.009 89790 SIGLEC10 0.65 0.004 10252 SPRY1 0.65 0.003 91544 UBXD5 0.65 0.001 116987 CENTG2 0.65 0.004 57447 NDRG2 0.65 0.003 285362 SUMF1 0.65 0.003 64866 CDCP1 0.65 0.002 91662 NLRP12 0.65 0.009 54830 NUP62CL 0.65 0.006 84133 ZNRF3 0.65 0.007 283687 C15orf37 0.65 0.001 23151 DIP 0.65 0.007 3579 IL8RB 0.65 0.001 116362 RBP7 0.65 0.001 57091 C20orf32 0.64 0.006 3914 LAMB3 0.64 0.004 132 ADK 0.64 0.004 79754 ASB13 0.64 0.003 2204 FCAR 0.64 0.009 57209 ZNF248 0.64 0.002 2878 GPX3 0.64 0.006 11200 CHEK2 0.64 0.003 51776 ZAK 0.64 0.003 51186 WBP5 0.64 0.005 9467 SH3BP5 0.64 0.001 6385 SDC4 0.64 0.005 949 SCARB1 0.63 0.002 27143 KIAA1274 0.63 0.002 11041 B3GNT1 0.63 0.003 134145 LOC134145 0.63 0.004 26115 TANC2 0.63 0.007 8555 CDC14B 0.63 0.007 57685 CACHD1 0.63 0.009 84106 PRAM1 0.63 0.009 4810 NHS 0.63 0.005 90427 BMF 0.63 0.006 29060 HSPC047 0.63 0.003 84525 HOP 0.62 0.000 57460 PPM1H 0.62 0.004 83953 FCAMR 0.62 0.002 6884 TAF13 0.62 0.003 8829 NRP1 0.62 0.006 54360 CYTL1 0.62 0.008 271 AMPD2 0.62 0.000 1687 DFNA5 0.62 0.003 64798 DEPDC6 0.62 0.002 27076 LYPD3 0.62 0.003 5980 REV3L 0.62 0.000

440712 C1orf186 0.62 0.001 80210 ARMC9 0.62 0.009 4774 NFIA 0.62 0.004 93145 OLFM2 0.62 0.002 3915 LAMC1 0.62 0.009 55972 SLC25A40 0.62 0.004 80856 KIAA1715 0.62 0.003 51449 PCYOX1 0.62 0.007 55351 STK32B 0.62 0.006 2065 ERBB3 0.62 0.002 6383 SDC2 0.61 0.009 3685 ITGAV 0.61 0.002 5864 RAB3A 0.61 0.002 8644 AKR1C3 0.61 0.009 57089 ENTPD7 0.61 0.002 51495 PTPLAD1 0.61 0.001 8082 SSPN 0.61 0.006 120224 TMEM45B 0.61 0.001 4753 NELL2 0.61 0.008 284756 C20orf197 0.61 0.004 90627 STARD13 0.60 0.000 161582 DYX1C1 0.60 0.009 79843 FAM124B 0.60 0.003 48 ACO1 0.60 0.002 50856 CLEC4A 0.60 0.002 80832 APOL4 0.60 0.009 123016 TTC8 0.60 0.007 50486 G0S2 0.60 0.002 152273 FGD5 0.60 0.009 7433 VIPR1 0.59 0.002 5955 RCN2 0.59 0.000 3772 KCNJ15 0.59 0.000 5738 PTGFRN 0.59 0.001 388115 C15orf52 0.58 0.003 6584 SLC22A5 0.58 0.002 166929 SGMS2 0.58 0.007 51561 IL23A 0.58 0.001 2170 FABP3 0.57 0.010 9060 PAPSS2 0.57 0.003 23314 SATB2 0.57 0.003 3034 HAL 0.57 0.000 26027 ACOT11 0.57 0.005 202309 C5orf29 0.57 0.001 4038 LRP4 0.57 0.003 8460 TPST1 0.57 0.007 23492 CBX7 0.56 0.000 22822 PHLDA1 0.56 0.007 4900 NRGN 0.56 0.006 4128 MAOA 0.56 0.004 911 CD1C 0.56 0.007 123041 SLC24A4 0.56 0.001 2203 FBP1 0.56 0.001

1184 CLCN5 0.56 0.002 8972 MGAM 0.56 0.003 23657 SLC7A11 0.55 0.003 23316 CUTL2 0.55 0.003 5208 PFKFB2 0.54 0.000 11057 ABHD2 0.54 0.003 91947 ARRDC4 0.54 0.000 53829 P2RY13 0.54 0.003 56034 PDGFC 0.53 0.006 2675 GFRA2 0.53 0.003 3992 FADS1 0.53 0.002 3092 HIP1 0.53 0.003 338094 C1orf179 0.52 0.002 10371 SEMA3A 0.52 0.007 8600 TNFSF11 0.52 0.002 8876 VNN1 0.52 0.006 55033 FKBP14 0.51 0.001 65124 ANKRD57 0.51 0.001 55 ACPP 0.51 0.000 1378 CR1 0.51 0.005 4023 LPL 0.50 0.010 6812 STXBP1 0.50 0.002 3552 IL1A 0.50 0.003 51313 C4orf18 0.49 0.002 1368 CPM 0.49 0.002 5028 P2RY1 0.49 0.002 91614 DEPDC7 0.49 0.000 23462 HEY1 0.48 0.009 167838 TXLNB 0.47 0.004 55799 CACNA2D3 0.47 0.002 1306 COL15A1 0.47 0.004 2152 F3 0.46 0.001 9586 CREB5 0.46 0.001 353324 SPATA12 0.46 0.008 26577 PCOLCE2 0.42 0.002 8309 ACOX2 0.41 0.001 55022 PID1 0.41 0.003 6769 STAC 0.40 0.006 79817 MOBKL2B 0.40 0.010 5054 SERPINE1 0.39 0.003 27197 GPR82 0.38 0.001 136 ADORA2B 0.37 0.002 22918 CD93 0.36 0.002 199675 C19orf59 0.35 0.002 26064 RAI14 0.35 0.004 2857 GPR34 0.35 0.001 23601 CLEC5A 0.35 0.001 9705 ST18 0.35 0.005 56670 SUCNR1 0.34 0.001 79689 STEAP4 0.34 0.004 338773 TMEM119 0.34 0.007 4060 LUM 0.34 0.001

7056 THBD 0.20 0.002

Supplementary Table IV

Top 10 canonical pathways as assessed by Ingenuity Pathway Analysis software from the 2850 genes differentially regulated in the healthy control EPCs/CACs treated by IFN-α compared to non-treated (q-value < 0.01).

Ingenuity Canonical Pathways p-value Molecules Interferon Signaling 3.98E-05 FNG, IFIT3, OAS1, MX1, IFNGR1, IFI35, IRF9, PSMB8, JAK2, TAP1, IFIT1, IFITM1, STAT2, IFNAR1 Altered T Cell and B Cell 3.24E-04 IFNG, RELA, TNFSF11, TRAF3, IL1A, IL10, RELB, IL15, Signaling in Rheumatoid Arthritis IL1F6, HLA-DMB, FAS, TNFRSF17, CD80, CXCL13, TGFB1, IL1RN, IL2, TLR7, HLA-DOB, IL1B, TLR3, IL23A, TNFSF13B, FASLG Activation of IRF by Cytosolic 1.00E-03 DHX58, RELA, TRAF3, IL10, NFKBIE, ZBP1, IRF9, Pattern Recognition Receptors IKBKE, ADAR, ISG15, TANK, IFIH1, IRF7, RIPK1, IFNA7, DDX58, STAT2, IKBKAP, IFIT2, IFNAR1 Molecular Mechanisms of 1.02E-03 PLCB2, TGFBR1, BAD, APH1B, SMAD3, CCND1, Cancer TGFB1, ARHGEF11, BRCA1, FZD2, SMAD1, FASLG, CASP10, TP53, PIK3C2B, CASP3, TFDP1, RALB, CDK6, GNAZ, AURKA, RALBP1, DAXX, CCND3, MAX, RND3, RABIF, PTPN11, PRKCD, IRS1, CDK4, E2F1, PRKACA, CFLAR, FNBP1, CAMK2G, RAP2A, MAP2K6, RELA, PA2G4, NFKBIE, GNA11, CTNNA1, BMPR2, PSEN2, PSENEN, SMAD5, JAK2, FAS, ARHGEF19, HHAT, NLK, SOS1, SMAD4, PRKCE, PIK3R2, ARHGEF3, MAP2K1, CHEK2, PRKDC, HAT1, RHOC, GNA12, DVL1, ADCY3, SMAD7, BAK1, NBN, FOS, PLCB4, PRKCI, PRKAG2, RBPJ, CASP7, PRKAR1A, PRKCB Role of Pattern Recognition 1.38E-03 RELA, PIK3C2B, OAS1, OAS2, IL10, MYD88, C5, OAS3 Receptors in Recognition of (includes EG:4940), IFIH1, IRF7, NOD2, TICAM1, IL2, 1

Bacteria and Viruses DDX58, CASP1, TLR7, NOD1, IL1B, PIK3R2, EIF2AK2, TLR3, NLRC4 Role of RIG1-like Receptors in 4.27E-03 DHX58, RELA, TRAF3, NFKBIE, IKBKE, TANK, IFIH1, Antiviral Innate Immunity TRAF2, IRF7, RIPK1, DDX58, IFNA7, TRIM25, CASP10 Role of CHK Proteins in Cell 4.47E-03 TP53, RFC4, E2F1, HUS1, RAD9A, SLC19A1, RPA1, Cycle Checkpoint Control TLK2, BRCA1, CHEK2, RFC3, NBN Pyruvate Metabolism 8.71E-03 AKR7A2, ACACB, ACAA1, IL21R, ACOT9, ALDH9A1, GLO1, ACSM5, ALDH1A3, BCKDHA, ALDH3A2, DLAT, ACSS2, ACYP1, ACACA, RWDD2B, PDHB, ACSL1, RWDD2A, ALDH7A1 Fatty Acid Elongation in 9.33E-03 ACAA1, PPT1, AUH, PECR, SDS, HSD17B4, HADH Mitochondria Cell Cycle: G1/S Checkpoint 1.10E-02 TP53, PA2G4, TFDP1, SMAD3, CUL1, HDAC1, CDK6, Regulation SKP1, CCND1, HDAC6, MAX, CCND3, TGFB1, CDK4, E2F1, SMAD4

Top 10 canonical pathways as assessed by Ingenuity Pathway Analysis software from the 1631 genes differentially regulated in the lupus EPCs/CACs exposed to IFN-α compared to non-exposed (q-value < 0.05, fold-change ≥ 0.15).

Ingenuity Canonical Pathways p-value Molecules Interferon Signaling 5.75E-07 IFIT3, SOCS1, IFNG, OAS1, MX1, IFI35, IRF9, PSMB8, JAK2, TAP1, IFIT1, IFITM1, STAT2 Role of Pattern Recognition 1.58E-06 PIK3C2B, OAS1, OAS2, IL10, MYD88, MAPK3, C5, IL6, Receptors in Recognition of OAS3 (includes EG:4940), IFIH1, IRF7, NOD2, TLR5, Bacteria and Viruses DDX58, TLR6, CASP1, TLR7, NOD1, IL1B, EIF2AK2, TLR3 Altered T Cell and B Cell 3.72E-05 IFNG, IL1A, IL10, IL15, IL6, FAS, TNFRSF17, CD40, Signaling in Rheumatoid Arthritis TLR5, CD80, CXCL13, IL1RN, TLR6, TLR7, HLA-DOB, IL1B, TLR3, TNFSF13B, FASLG TREM1 Signaling 1.29E-04 IL10, MAPK3, STAT3, JAK2, IL6, NOD2, TLR5, CCL7, CD40, TLR6, TLR7, CASP1, IL1B, TLR3, CASP5 Activation of IRF by Cytosolic 1.32E-04 DHX58, IL10, ZBP1, IKBKE, IRF9, IL6, ISG15, TANK, Pattern Recognition Receptors IFIH1, IRF7, RIPK1, CD40, DDX58, IKBKAP, STAT2, IFIT2 Retinoic acid Mediated 1.58E-04 CASP9, PARP10, PARP15, CASP3, PARP8, TNFSF10, Apoptosis Signaling PARP11, CFLAR, PARP12, TNFRSF10A (includes EG:8797), PARP9, PARP14 Communication between Innate 3.63E-04 IFNG, IL1A, IL10, IL15, IL6, TNFRSF17, CXCL10, TLR5, and Adaptive Immune Cells CD80, CD40, IL1RN, TLR6, TLR7, IL1B, TLR3, TNFSF13B

Crosstalk between Dendritic 5.50E-04 IFNG, IL15RA, KLRD1, CD69, ACTA2, IL15, TNFSF10, Cells and Natural Killer Cells IL6, TREM2, FAS, CAMK2D, CD40, CD80, MICB, TLR7, TLR3, FASLG, CAMK2G, PVRL2 Graft-versus-Host Disease 1.35E-03 IFNG, IL1A, CD80, IL1RN, HLA-DOB, IL1B, IL6, FAS, Signaling FASLG, GZMB Death Receptor Signaling 3.09E-03 CASP3, TNFSF10, IKBKE, XIAP, FAS, TANK, TRADD, RIPK1, CASP9, CFLAR, TNFRSF10A (includes EG:8797), CASP7, FASLG

Top 10 canonical pathways as assessed by Ingenuity Pathway Analysis software from the 710 genes differentially regulated in the healthy CD133+ bone marrow EPCs treated with IFN-α compared to non-treated (q-value < 0.05).

Ingenuity Canonical Pathways p-value Molecules Interferon Signaling 6.76E-10 IFIT3, IFIT1, OAS1, IFITM1, MX1, IFI35, STAT2, IRF9, PSMB8, JAK2, STAT1, TAP1 Role of Pattern Recognition 6.92E-10 PIK3C2B, OAS1, OAS2, IL10, MYD88, C1QC, IL6, OAS3 Receptors in Recognition of (includes EG:4940), TLR2, IFIH1, IRF7, DDX58, CASP1, Bacteria and Viruses TLR7, NOD1, EIF2AK2, TLR3, C3AR1 Activation of IRF by Cytosolic 2.09E-07 DHX58, IL10, ZBP1, IRF9, IL6, ADAR, ISG15, IFIH1, Pattern Recognition Receptors IRF7, RIPK1, DDX58, STAT2, IFIT2, STAT1 Antigen Presentation Pathway 1.74E-06 PSMB9, HLA-E, HLA-DOB, PSMB8, TAP1, TAP2, TAPBP, MR1, HLA-F Pathogenesis of Multiple 1.70E-05 CXCL10, CCR1, CCR5, CXCL9, CXCL11 Sclerosis Retinoic acid Mediated 2.82E-05 PARP10, PARP15, PARP8, TNFSF10, PARP11, CFLAR, Apoptosis Signaling PARP12, PARP9, PARP14 Altered T Cell and B Cell 5.89E-05 TLR2, CD80, IL10, IL1RN, IL15, TLR7, CD86, HLA-DOB, Signaling in Rheumatoid Arthritis IL6, TLR3, TNFSF13B, FAS TREM1 Signaling 9.55E-05 TLR2, CCL7, IL10, TLR7, CASP1, CD86, JAK2, IL6, TLR3, FCGR2B Graft-versus-Host Disease 1.02E-04 CD80, HLA-E, IL1RN, CD86, HLA-DOB, IL6, FAS, HLA-F Signaling Communication between Innate 1.02E-04 CXCL10, TLR2, CD80, IL10, IL1RN, IL15, TLR7, CD86, and Adaptive Immune Cells IL6, TLR3, TNFSF13B

Supplementary table V: Genes directly connected to IL-1β

Entrez Gene LogFC FC q-

Gene symbol Gene name SAM SAM value

3553 IL1B interleukin 1, beta -0,685 0,622 0,001

10855 HPSE heparanase 1,581 2,993 0,000

2358 FPR2 formyl peptide receptor 2 1,366 2,578 0,003

23786 BCL2L13 BCL2-like 13 (apoptosis facilitator) 0,706 1,632 0,000

1728 NQO1 NAD(P)H dehydrogenase, quinone 1 -0,621 0,650 0,000

adhesion molecule, interacts with

120425 AMICA1 CXADR antigen 1 -0,725 0,605 0,000

1890 TYMP thymidine phosphorylase 1,574 2,976 0,000

solute carrier family 4, sodium

9497 SLC4A7 bicarbonate cotransporter, member 7 -0,599 0,660 0,000

10333 TLR6 toll-like receptor 6 -0,722 0,606 0,001

3600 IL15 interleukin 15 1,947 3,856 0,001

24145 PANX1 pannexin 1 1,676 3,195 0,000

3665 IRF7 interferon regulatory factor 7 2,013 4,037 0,000

3660 IRF2 interferon regulatory factor 2 0,717 1,644 0,000

3667 IRS1 insulin receptor substrate 1 0,677 1,599 0,036

integrin, alpha 2 (CD49B, alpha 2 subunit

3673 ITGA2 of VLA-2 receptor) 1,043 2,060 0,001

3655 ITGA6 integrin, alpha 6 -0,887 0,541 0,008

3620 INDO indoleamine-pyrrole 2,3 dioxygenase 2,392 5,248 0,000

3627 CXCL10 chemokine (C-X-C motif) ligand 10 1,616 3,066 0,013

3001 GZMA granzyme A (granzyme 1, cytotoxic T- 0,719 1,646 0,001 lymphocyte-associated serine esterase 3)

1672 DEFB1 defensin, beta 1 5,734 53,222 0,000

3586 IL10 interleukin 10 0,776 1,712 0,000

9592 IER2 immediate early response 2 0,691 1,614 0,001

inhibitor of kappa light polypeptide gene

9641 IKBKE enhancer in B-cells, kinase epsilon 0,684 1,607 0,000

9672 SDC3 syndecan 3 0,697 1,621 0,006

9636 ISG15 ISG15 ubiquitin-like modifier 3,181 9,069 0,000

3557 IL1RN interleukin 1 receptor antagonist 3,457 10,980 0,000

3569 IL6 interleukin 6 (interferon, beta 2) 1,083 2,118 0,001

3570 IL6R interleukin 6 receptor 0,615 1,531 0,000

3577 IL8RA interleukin 8 receptor, alpha -0,773 0,585 0,003

3574 IL7 interleukin 7 2,182 4,539 0,000

3575 IL7R interleukin 7 receptor 0,997 1,995 0,002

3579 IL8RB interleukin 8 receptor, beta -0,713 0,610 0,002

nucleotide-binding oligomerization

10392 NOD1 domain containing 1 0,920 1,893 0,000

29126 CD274 CD274 molecule 2,190 4,563 0,001

ribosomal protein S6 kinase, 90kDa,

9252 RPS6KA5 polypeptide 5 0,771 1,707 0,002

55655 NLRP2 NLR family, pyrin domain containing 2 -0,641 0,641 0,003

1803 DPP4 dipeptidyl-peptidase 4 1,274 2,418 0,002

30009 TBX21 T-box 21 0,619 1,535 0,020

9373 PLAA phospholipase A2-activating protein 0,671 1,592 0,000

57758 SCUBE2 signal peptide, CUB domain, EGF-like 2 1,747 3,357 0,000 3717 JAK2 Janus kinase 2 (a protein tyrosine kinase) 2,189 4,559 0,000

caspase 5, apoptosis-related cysteine

838 CASP5 peptidase 0,946 1,926 0,001

831 CAST calpastatin 0,613 1,530 0,000

caspase 1, apoptosis-related cysteine

834 CASP1 peptidase (interleukin 1, beta, convertase) 0,654 1,573 0,000

caspase 3, apoptosis-related cysteine

836 CASP3 peptidase 0,966 1,953 0,000

caspase 7, apoptosis-related cysteine

840 CASP7 peptidase 1,354 2,556 0,000

caspase 9, apoptosis-related cysteine

842 CASP9 peptidase -0,623 0,649 0,001

3431 SP110 SP110 nuclear body protein 2,081 4,232 0,000

guanylate binding protein 1, interferon-

2633 GBP1 inducible, 67kDa 1,697 3,243 0,004

proline-serine-threonine phosphatase

9051 PSTPIP1 interacting protein 1 -0,691 0,619 0,002

952 CD38 CD38 molecule 2,649 6,270 0,000

CD40 molecule, TNF receptor

958 CD40 superfamily member 5 1,349 2,547 0,001

962 CD48 CD48 molecule 0,839 1,789 0,001

969 CD69 CD69 molecule 1,497 2,822 0,001

961 CD47 CD47 molecule 0,924 1,897 0,000

tumor necrosis factor receptor

943 TNFRSF8 superfamily, member 8 -0,791 0,578 0,001 941 CD80 CD80 molecule 2,141 4,411 0,000

9124 PDLIM1 PDZ and LIM domain 1 0,634 1,552 0,001

nucleotide-binding oligomerization

64127 NOD2 domain containing 2 0,666 1,587 0,001

629 CFB complement factor B 3,138 8,803 0,000

688 KLF5 Kruppel-like factor 5 (intestinal) 0,938 1,916 0,001

complement component 1, r

715 C1R subcomponent 0,947 1,928 0,003

complement component 1, s

716 C1S subcomponent 0,978 1,970 0,004

717 C2 complement component 2 0,676 1,597 0,018

7414 VCL vinculin -0,850 0,555 0,000

10346 TRIM22 tripartite motif-containing 22 1,314 2,486 0,000

3084 NRG1 neuregulin 1 -0,799 0,575 0,008

7430 EZR ezrin 0,965 1,951 0,000

transient receptor potential cation channel,

7442 TRPV1 subfamily V, member 1 -1,475 0,360 0,000

2643 GCH1 GTP cyclohydrolase 1 1,332 2,518 0,001

2621 GAS6 growth arrest-specific 6 0,725 1,652 0,001

tumor necrosis factor, alpha-induced

7130 TNFAIP6 protein 6 1,144 2,209 0,001

7100 TLR5 toll-like receptor 5 -0,798 0,575 0,002

3429 IFI27 interferon, alpha-inducible protein 27 2,103 4,296 0,002

fucosyltransferase 4 (alpha (1,3)

2526 FUT4 fucosyltransferase, myeloid-specific) 1,512 2,852 0,000 7056 THBD thrombomodulin -1,361 0,389 0,000

7058 THBS2 thrombospondin 2 -0,818 0,567 0,002

7098 TLR3 toll-like receptor 3 4,598 24,223 0,000

7082 TJP1 tight junction protein 1 (zona occludens 1) 1,030 2,042 0,000

TIA1 cytotoxic granule-associated RNA

7072 TIA1 binding protein 0,965 1,953 0,000

protein phosphatase 2A activator,

5524 PPP2R4 regulatory subunit 4 0,765 1,700 0,000

5581 PRKCE protein kinase C, epsilon 1,264 2,401 0,000

5595 MAPK3 mitogen-activated protein kinase 3 -0,676 0,626 0,000

granzyme B (granzyme 2, cytotoxic T-

3002 GZMB lymphocyte-associated serine esterase 1) 0,953 1,936 0,002

3552 IL1A interleukin 1, alpha -1,211 0,432 0,001

proteasome (prosome, macropain)

subunit, beta type, 9 (large multifunctional

5698 PSMB9 peptidase 2) 0,786 1,725 0,002

proteasome (prosome, macropain)

subunit, beta type, 8 (large multifunctional

5696 PSMB8 peptidase 7) 0,997 1,996 0,000

2119 ETV5 ets variant gene 5 (ets-related molecule) -0,735 0,601 0,000

eukaryotic translation initiation factor 2-

5610 EIF2AK2 alpha kinase 2 1,660 3,160 0,000

excision repair cross-complementing

rodent repair deficiency, complementation

2068 ERCC2 group 2 -0,805 0,573 0,001 5608 MAP2K6 mitogen-activated protein kinase kinase 6 1,858 3,625 0,000

5341 PLEK pleckstrin 0,621 1,538 0,000

5359 PLSCR1 phospholipid scramblase 1 1,492 2,813 0,000

5362 PLXNA2 plexin A2 -0,799 0,575 0,004

peroxisome proliferator-activated receptor

5468 PPARG gamma -1,974 0,255 0,000

DEAD (Asp-Glu-Ala-Asp) box

23586 DDX58 polypeptide 58 3,174 9,026 0,000

platelet-derived growth factor beta

polypeptide (simian sarcoma viral (v-sis)

5155 PDGFB oncogene homolog) 0,893 1,857 0,000

phosphodiesterase 4B, cAMP-specific

(phosphodiesterase E4 dunce homolog,

5142 PDE4B Drosophila) 0,932 1,907 0,001

serpin peptidase inhibitor, clade F (alpha-

SERPINF 2 antiplasmin, pigment epithelium derived

5176 1 factor), member 1 -0,648 0,638 0,004

ectonucleotide

5168 ENPP2 pyrophosphatase/phosphodiesterase 2 1,333 2,519 0,001

2185 PTK2B PTK2B protein tyrosine kinase 2 beta 0,972 1,962 0,000

MARCKS

65108 L1 MARCKS-like 1 -0,801 0,574 0,000

3430 IFI35 interferon-induced protein 35 2,388 5,236 0,000

purinergic receptor P2Y, G-protein

5029 P2RY2 coupled, 2 -0,929 0,525 0,000 ATP-binding cassette, sub-family D

215 ABCD1 (ALD), member 1 1,021 2,029 0,000

1316 KLF6 Kruppel-like factor 6 1,308 2,476 0,000

receptor-interacting serine-threonine

11035 RIPK3 kinase 3 0,648 1,567 0,000

TRAF family member-associated NFKB

10010 TANK activator 0,631 1,549 0,002

RNA binding motif, single stranded

5937 RBMS1 interacting protein 1 0,856 1,811 0,000

5979 RET ret proto-oncogene 1,810 3,507 0,009

5747 PTK2 PTK2 protein tyrosine kinase 2 0,800 1,742 0,002

prostaglandin-endoperoxide synthase 1

(prostaglandin G/H synthase and

5742 PTGS1 cyclooxygenase) -0,924 0,527 0,000

5829 PXN paxillin -0,730 0,603 0,000

1540 CYLD cylindromatosis (turban tumor syndrome) 0,739 1,670 0,001

3458 IFNG interferon, gamma 1,273 2,417 0,010

22918 CD93 CD93 molecule -1,206 0,433 0,000

Fas (TNF receptor superfamily, member

355 FAS 6) 1,805 3,495 0,000

331 XIAP X-linked inhibitor of apoptosis 0,612 1,529 0,000

8651 SOCS1 suppressor of cytokine signaling 1 0,914 1,884 0,001

8642 DCHS1 dachsous 1 (Drosophila) -0,693 0,619 0,002

2332 FMR1 fragile X mental retardation 1 0,678 1,600 0,000

8714 ABCC3 ATP-binding cassette, sub-family C -0,825 0,565 0,000 (CFTR/MRP), member 3

tumor necrosis factor (ligand)

8744 TNFSF9 superfamily, member 9 -0,727 0,604 0,001

tumor necrosis factor (ligand)

8743 TNFSF10 superfamily, member 10 3,291 9,788 0,000

2069 EREG epiregulin 0,636 1,554 0,018

246778 IL27 interleukin 27 0,930 1,905 0,000

3075 CFH complement factor H 2,626 6,171 0,000

3925 STMN1 stathmin 1/oncoprotein 18 -1,593 0,332 0,000

3965 LGALS9 lectin, galactoside-binding, soluble, 9 1,206 2,306 0,000

triggering receptor expressed on myeloid

54209 TREM2 cells 2 -0,881 0,543 0,000

relaxin/insulin-like family peptide

59350 RXFP1 receptor 1 0,765 1,700 0,004

heat shock 70kDa protein 5 (glucose-

3309 HSPA5 regulated protein, 78kDa) -0,787 0,580 0,000

1306 COL15A1 collagen, type XV, alpha 1 -1,195 0,437 0,001

2026 ENO2 enolase 2 (gamma, neuronal) -0,933 0,524 0,000

coagulation factor III (thromboplastin,

2152 F3 tissue factor) -0,754 0,593 0,001

cytochrome P450, family 19, subfamily

1588 CYP19A1 A, polypeptide 1 1,075 2,107 0,006

4086 SMAD1 SMAD family member 1 1,420 2,675 0,000

myristoylated alanine-rich protein kinase

4082 MARCKS C substrate 0,749 1,680 0,000 4088 SMAD3 SMAD family member 3 0,907 1,876 0,000

4048 LTA4H leukotriene A4 hydrolase -0,614 0,653 0,000

ribosomal protein S6 kinase, 90kDa,

6195 RPS6KA1 polypeptide 1 -0,799 0,575 0,000

latent transforming growth factor beta

4053 LTBP2 binding protein 2 -0,995 0,502 0,000

v-yes-1 Yamaguchi sarcoma viral related

4067 LYN oncogene homolog 0,946 1,927 0,000

4012 LNPEP leucyl/cystinyl aminopeptidase 1,486 2,802 0,000

4023 LPL lipoprotein lipase -2,032 0,245 0,000

390 RND3 Rho family GTPase 3 1,666 3,174 0,000

356 FASLG Fas ligand (TNF superfamily, member 6) 0,918 1,889 0,006

6285 S100B S100 calcium binding protein B -0,905 0,534 0,000

2 A2M alpha-2-macroglobulin -1,126 0,458 0,002

chemokine (C-X-C motif) ligand 12

6387 CXCL12 (stromal cell-derived factor 1) 1,268 2,408 0,000

6385 SDC4 syndecan 4 -0,868 0,548 0,000

6383 SDC2 syndecan 2 -0,696 0,617 0,000

6373 CXCL11 chemokine (C-X-C motif) ligand 11 5,523 45,968 0,000

6363 CCL19 chemokine (C-C motif) ligand 19 0,852 1,805 0,001

interferon-induced protein with

24138 IFIT5 tetratricopeptide repeats 5 1,386 2,614 0,000

6354 CCL7 chemokine (C-C motif) ligand 7 1,585 3,000 0,002

6355 CCL8 chemokine (C-C motif) ligand 8 1,627 3,088 0,003

6357 CCL13 chemokine (C-C motif) ligand 13 1,817 3,523 0,004 HLA- major histocompatibility complex, class

3112 DOB II, DO beta 1,033 2,046 0,002

MHC class I polypeptide-related sequence

4277 MICB B 0,721 1,649 0,000

4283 CXCL9 chemokine (C-X-C motif) ligand 9 1,564 2,956 0,010

4299 AFF1 AF4/FMR2 family, member 1 0,973 1,963 0,000

4210 MEFV Mediterranean fever 0,913 1,883 0,001

mitogen-activated protein kinase kinase

4215 MAP3K3 kinase 3 -0,699 0,616 0,000

578 BAK1 BCL2-antagonist/killer 1 0,731 1,659 0,001

6402 SELL selectin L 1,121 2,176 0,000

chemokine (C-X-C motif) ligand 13 (B-

10563 CXCL13 cell chemoattractant) 1,156 2,228 0,000

solute carrier family 3 (cystine, dibasic

and neutral amino acid transporters,

activator of cystine, dibasic and neutral

6519 SLC3A1 amino acid transport), member 1 -0,642 0,641 0,024

467 ATF3 activating transcription factor 3 1,494 2,817 0,000

4303 FOXO4 forkhead box O4 -0,701 0,615 0,000

solute carrier family 8 (sodium/calcium

6546 SLC8A1 exchanger), member 1 1,620 3,073 0,000

stress-associated endoplasmic reticulum

387923 SERP2 protein family member 2 -0,795 0,576 0,006

51284 TLR7 toll-like receptor 7 0,598 1,513 0,008

6692 SPINT1 serine peptidase inhibitor, Kunitz type 1 -0,899 0,536 0,000 6654 SOS1 son of sevenless homolog 1 (Drosophila) 1,054 2,076 0,000

51274 KLF3 Kruppel-like factor 3 (basic) 0,826 1,773 0,000

51191 HERC5 hect domain and RLD 5 3,012 8,068 0,000

signal transducer and activator of

transcription 3 (acute-phase response

6774 STAT3 factor) 0,625 1,542 0,001

transporter 2, ATP-binding cassette, sub-

6891 TAP2 family B (MDR/TAP) 1,704 3,259 0,001

4860 NP nucleoside phosphorylase -0,678 0,625 0,000

4854 NOTCH3 Notch homolog 3 (Drosophila) -0,951 0,517 0,001

153222 C5orf41 chromosome 5 open reading frame 41 0,955 1,939 0,001

2'-5'-oligoadenylate synthetase 2,

4939 OAS2 69/71kDa 3,229 9,374 0,000

fatty acid binding protein 3, muscle and

2170 FABP3 heart (mammary-derived growth inhibitor) -1,202 0,435 0,000

51540 SCLY selenocysteine lyase -0,973 0,509 0,000

insulin-like growth factor binding protein

3487 IGFBP4 4 2,896 7,444 0,000

angiotensin I converting enzyme

1636 ACE (peptidyl-dipeptidase A) 1 0,690 1,613 0,000

sterile alpha motif and leucine zipper

51776 ZAK containing kinase AZK -0,736 0,601 0,000

4481 MSR1 macrophage scavenger receptor 1 1,534 2,897 0,000

CASP8 and FADD-like apoptosis

8837 CFLAR regulator 0,846 1,798 0,000 8809 IL18R1 interleukin 18 receptor 1 0,833 1,782 0,010

8829 NRP1 neuropilin 1 -0,703 0,614 0,000

4502 MT2A metallothionein 2A 1,095 2,137 0,004

myxovirus (influenza virus) resistance 1,

4599 MX1 interferon-inducible protein p78 (mouse) 2,585 6,000 0,000

4582 MUC1 mucin 1, cell surface associated 2,111 4,320 0,000

GADD45 growth arrest and DNA-damage-

4616 B inducible, beta 0,764 1,698 0,000

myeloid differentiation primary response

4615 MYD88 gene (88) 0,706 1,632 0,000

myxovirus (influenza virus) resistance 2

4600 MX2 (mouse) 2,656 6,302 0,000

2203 FBP1 fructose-1,6-bisphosphatase 1 -0,764 0,589 0,000

1906 EDN1 endothelin 1 0,689 1,613 0,007

leukocyte immunoglobulin-like receptor,

subfamily A (with TM domain), member

353514 LILRA5 5 1,874 3,667 0,001

Supplementary Table VI

1631 genes differentially regulated in the lupus EPCs/CACs exposed to IFN-α compared to non-exposed (q-value < 0.05, fold-change ≥ 0.15). Gene ID Gene symbol Fold-change q-value 1672 DEFB1 53.22 0.000 6373 CXCL11 45.97 0.000 8820 HESX1 35.48 0.000 2766 GMPR 30.43 0.000 7098 TLR3 24.22 0.000 5157 PDGFRL 20.07 0.000 91624 NEXN 18.49 0.000 57088 PLSCR4 17.29 0.000 8638 OASL 16.31 0.000 23052 ENDOD1 15.37 0.000 85477 SCIN 13.53 0.000 23034 SAMD4A 12.85 0.000 152926 PPM1K 12.73 0.000 84941 HSH2D 12.61 0.000 3437 IFIT3 12.21 0.000 81030 ZBP1 11.80 0.000 51513 ETV7 10.98 0.000 3557 IL1RN 10.98 0.000 85413 SLC22A16 10.35 0.000 10964 IFI44L 9.92 0.000 8743 TNFSF10 9.79 0.000 3902 LAG3 9.75 0.000 4939 OAS2 9.37 0.000 1832 DSP 9.32 0.000 55008 HERC6 9.25 0.000 64762 FAM59A 9.23 0.000 9636 ISG15 9.07 0.000 23586 DDX58 9.03 0.000 629 CFB 8.80 0.000 4061 LY6E 8.49 0.000 65987 KCTD14 8.47 0.000 3434 IFIT1 8.44 0.000 87178 PNPT1 8.41 0.000 8900 CCNA1 8.32 0.000 79132 DHX58 8.21 0.000 51191 HERC5 8.07 0.000 3433 IFIT2 7.92 0.000 729034 LOC729034 7.85 0.000 4938 OAS1 7.84 0.000 200315 APOBEC3A 7.71 0.000 3669 ISG20 7.65 0.000 3487 IGFBP4 7.44 0.000 2537 IFI6 7.22 0.000 57493 HEG1 7.16 0.000 51251 NT5C3 7.06 0.000 1

3728 JUP 6.96 0.000 64108 RTP4 6.86 0.000 115361 GBP4 6.74 0.001 91543 RSAD2 6.74 0.000 11145 PLA2G16 6.45 0.000 9517 SPTLC2 6.40 0.000 4600 MX2 6.30 0.000 952 CD38 6.27 0.000 4940 OAS3 6.27 0.000 3075 CFH 6.17 0.000 255231 MCOLN2 6.04 0.000 4599 MX1 6.00 0.000 93082 NEURL3 5.99 0.000 558 AXL 5.97 0.000 1379 CR1L 5.94 0.000 9447 AIM2 5.81 0.001 286334 LOC286334 5.76 0.000 116071 BATF2 5.61 0.001 221711 SYCP2L 5.54 0.001 5939 RBMS2 5.43 0.000 114991 ZNF618 5.40 0.000 165631 PARP15 5.36 0.000 3620 IDO1 5.25 0.000 26228 STAP1 5.24 0.000 162394 SLFN5 5.24 0.000 3430 IFI35 5.24 0.000 3601 IL15RA 5.22 0.000 85441 PRIC285 5.03 0.000 26010 SPATS2L 5.03 0.000 400941 FLJ42418 5.02 0.000 54809 SAMD9 5.02 0.000 10643 IGF2BP3 4.97 0.000 80380 PDCD1LG2 4.92 0.000 873 CBR1 4.87 0.000 9910 RABGAP1L 4.87 0.000 2867 FFAR2 4.73 0.000 344018 FIGLA 4.73 0.008 257019 FRMD3 4.70 0.000 219285 SAMD9L 4.65 0.000 653464 SRGAP2P1 4.62 0.000 11262 SP140 4.61 0.000 57714 KIAA1618 4.59 0.000 29126 CD274 4.56 0.001 3717 JAK2 4.56 0.000 3574 IL7 4.54 0.000 710 SERPING1 4.48 0.001 375346 TMEM110 4.45 0.000 55615 PRR5 4.42 0.000 941 CD80 4.41 0.000 684 BST2 4.40 0.000 145864 HAPLN3 4.39 0.001 4582 MUC1 4.32 0.000

3429 IFI27 4.30 0.002 116843 C6orf192 4.28 0.000 113730 KLHDC7B 4.27 0.000 151556 GPR155 4.24 0.000 3431 SP110 4.23 0.000 57648 KIAA1522 4.19 0.000 8519 IFITM1 4.17 0.001 3959 LGALS3BP 4.14 0.000 54739 XAF1 4.09 0.000 9674 KIAA0040 4.08 0.000 199223 TTC21A 4.08 0.000 80055 PGAP1 4.05 0.000 3665 IRF7 4.04 0.000 200316 APOBEC3F 4.02 0.000 10791 VAMP5 3.98 0.000 55509 BATF3 3.98 0.001 123872 LRRC50 3.96 0.001 159091 FAM122C 3.95 0.000 5371 PML 3.91 0.000 26270 FBXO6 3.90 0.000 3600 IL15 3.86 0.001 23682 RAB38 3.83 0.000 4343 MOV10 3.76 0.000 317649 EIF4E3 3.74 0.000 55014 STX17 3.73 0.000 55603 FAM46A 3.72 0.000 256227 MGC87042 3.70 0.000 55501 CHST12 3.69 0.000 353514 LILRA5 3.67 0.001 9881 LBA1 3.66 0.000 55711 FAR2 3.66 0.000 7318 UBA7 3.64 0.000 5608 MAP2K6 3.63 0.000 4499 MT1M 3.60 0.001 375287 RBM43 3.60 0.000 23380 SRGAP2 3.58 0.000 730249 IRG1 3.58 0.007 8542 APOL1 3.53 0.000 84628 NTNG2 3.53 0.000 6357 CCL13 3.52 0.004 5979 RET 3.51 0.009 2982 GUCY1A3 3.51 0.000 10133 OPTN 3.50 0.000 355 FAS 3.49 0.000 54877 ZCCHC2 3.46 0.000 143888 KDELC2 3.45 0.000 634 CEACAM1 3.44 0.000 10561 IFI44 3.42 0.000 6614 SIGLEC1 3.41 0.001 259307 IL4I1 3.41 0.000 85363 TRIM5 3.40 0.000 441108 C5orf56 3.39 0.000

11000 SLC27A3 3.38 0.000 64135 IFIH1 3.37 0.000 83401 ELOVL3 3.37 0.005 10993 SDS 3.36 0.000 57758 SCUBE2 3.36 0.000 64853 AIDA 3.35 0.000 23424 TDRD7 3.31 0.000 5420 PODXL 3.30 0.001 9023 CH25H 3.29 0.005 580 BARD1 3.27 0.000 6891 TAP2 3.26 0.001 2633 GBP1 3.24 0.004 114879 OSBPL5 3.24 0.000 6398 SECTM1 3.23 0.000 4001 LMNB1 3.23 0.000 4332 MNDA 3.22 0.000 55601 DDX60 3.20 0.000 132864 CPEB2 3.20 0.000 24145 PANX1 3.20 0.000 4651 MYO10 3.19 0.000 135112 NCOA7 3.19 0.000 84930 MASTL 3.18 0.000 390 RND3 3.17 0.000 7051 TGM1 3.17 0.001 5610 EIF2AK2 3.16 0.000 26471 NUPR1 3.13 0.000 55300 PI4K2B 3.13 0.000 55106 SLFN12 3.12 0.000 375035 SFT2D2 3.10 0.000 56913 C1GALT1 3.09 0.000 6355 CCL8 3.09 0.003 65220 NADK 3.08 0.000 54749 EPDR1 3.08 0.003 6546 SLC8A1 3.07 0.000 23347 SMCHD1 3.07 0.000 3627 CXCL10 3.07 0.013 57097 PARP11 3.01 0.000 94240 EPSTI1 3.00 0.000 6354 CCL7 3.00 0.002 57169 ZNFX1 2.99 0.000 10855 HPSE 2.99 0.000 85315 PAQR8 2.99 0.000 1890 TYMP 2.98 0.000 1847 DUSP5 2.98 0.001 115004 C6orf150 2.97 0.000 84441 MAML2 2.96 0.000 4283 CXCL9 2.96 0.010 79993 ELOVL7 2.95 0.000 27348 TOR1B 2.94 0.000 1152 CKB 2.93 0.002 10499 NCOA2 2.93 0.000 256236 NAPSB 2.92 0.000

10410 IFITM3 2.92 0.001 7453 WARS 2.90 0.001 59 ACTA2 2.90 0.001 4481 MSR1 2.90 0.000 143689 PIWIL4 2.89 0.001 56938 ARNTL2 2.89 0.000 AFFX- #N/A 2.89 0.004 HUMISGF3A/M97935_M A 25841 ABTB2 2.89 0.000 57823 SLAMF7 2.86 0.000 2650 GCNT1 2.85 0.000 2526 FUT4 2.85 0.000 7706 TRIM25 2.85 0.000 23508 TTC9 2.85 0.001 53826 FXYD6 2.84 0.000 9582 APOBEC3B 2.84 0.001 9830 TRIM14 2.84 0.000 969 CD69 2.82 0.001 467 ATF3 2.82 0.000 79056 PRRG4 2.82 0.000 5359 PLSCR1 2.81 0.000 139285 FAM123B 2.80 0.000 4012 LNPEP 2.80 0.000 219988 PATL1 2.79 0.000 9865 KIAA0644 2.79 0.012 54536 EXOC6 2.78 0.000 51427 ZNF107 2.77 0.000 23070 FTSJD2 2.76 0.000 8850 KAT2B 2.75 0.000 158219 TTC39B 2.74 0.000 9603 NFE2L3 2.73 0.000 160897 GPR180 2.73 0.000 22809 ATF5 2.72 0.000 55026 FAM70A 2.71 0.001 729810 LOC729810 2.70 0.000 6238 RRBP1 2.70 0.000 84560 MT4 2.69 0.000 80833 APOL3 2.69 0.002 4086 SMAD1 2.68 0.000 132320 SCLT1 2.65 0.000 23338 PHF15 2.65 0.000 116443 GRIN3A 2.64 0.000 80830 APOL6 2.63 0.002 659 BMPR2 2.63 0.000 6091 ROBO1 2.63 0.001 10970 CKAP4 2.62 0.000 117852 TRIMP1 2.61 0.000 24138 IFIT5 2.61 0.000 3700 ITIH4 2.61 0.000 114876 OSBPL1A 2.60 0.000 9414 TJP2 2.59 0.000

2358 FPR2 2.58 0.003 117854 TRIM6 2.58 0.000 441168 FAM26F 2.58 0.003 10616 RBCK1 2.57 0.000 9567 GTPBP1 2.57 0.000 389289 C5orf39 2.57 0.000 132321 C4orf33 2.56 0.000 153020 RASGEF1B 2.56 0.000 840 CASP7 2.56 0.000 23362 PSD3 2.55 0.000 116028 C16orf75 2.55 0.000 132720 C4orf32 2.55 0.000 958 CD40 2.55 0.001 10734 STAG3 2.54 0.000 728769 LOC728769 2.54 0.000 51479 ANKFY1 2.53 0.000 81622 UNC93B1 2.52 0.000 5168 ENPP2 2.52 0.001 2643 GCH1 2.52 0.001 9781 RNF144A 2.51 0.000 201175 SH3D20 2.50 0.000 2591 GALNT3 2.50 0.000 729839 LOC729839 2.49 0.000 2201 FBN2 2.49 0.001 10346 TRIM22 2.49 0.000 10673 TNFSF13B 2.48 0.000 1316 KLF6 2.48 0.000 51421 AMOTL2 2.47 0.004 1534 CYB561 2.46 0.000 91937 TIMD4 2.46 0.001 8775 NAPA 2.44 0.000 9997 SCO2 2.42 0.002 1803 DPP4 2.42 0.002 3458 IFNG 2.42 0.010 6387 CXCL12 2.41 0.000 5581 PRKCE 2.40 0.000 2131 EXT1 2.40 0.000 3097 HIVEP2 2.40 0.000 114793 FMNL2 2.40 0.000 59345 GNB4 2.39 0.000 1240 CMKLR1 2.39 0.000 139065 SLITRK4 2.38 0.001 23301 EHBP1 2.37 0.000 29761 USP25 2.37 0.000 9749 PHACTR2 2.37 0.000 957 ENTPD5 2.37 0.000 9465 AKAP7 2.36 0.000 84868 HAVCR2 2.36 0.000 54530 C1orf218 2.36 0.000 221079 ARL5B 2.36 0.000 10859 LILRB1 2.36 0.000 375790 AGRN 2.33 0.000

55024 BANK1 2.33 0.001 80821 DDHD1 2.33 0.000 8814 CDKL1 2.33 0.000 51023 MRPS18C 2.32 0.000 51280 GOLM1 2.32 0.000 84875 PARP10 2.32 0.000 9033 PKD2L1 2.32 0.001 389125 MUSTN1 2.31 0.000 3965 LGALS9 2.31 0.000 89853 FAM125B 2.31 0.000 139324 HDX 2.30 0.000 49855 SCAPER 2.29 0.000 6672 SP100 2.28 0.000 388228 SBK1 2.28 0.000 AFFX- #N/A 2.27 0.004 HUMISGF3A/M97935_M B 83666 PARP9 2.27 0.000 57168 ASPHD2 2.27 0.000 56829 ZC3HAV1 2.26 0.000 817 CAMK2D 2.26 0.000 64651 CSRNP1 2.26 0.000 151306 GPBAR1 2.26 0.000 81704 DOCK8 2.26 0.000 55337 C19orf66 2.25 0.000 3957 LGALS2 2.25 0.000 8807 IL18RAP 2.25 0.003 51493 C22orf28 2.25 0.000 79792 GSDMD 2.25 0.000 23328 SASH1 2.24 0.001 54734 RAB39 2.24 0.001 55839 CENPN 2.24 0.000 55326 AGPAT5 2.23 0.000 65979 PHACTR4 2.23 0.000 51701 NLK 2.23 0.000 10563 CXCL13 2.23 0.000 9246 UBE2L6 2.23 0.001 81894 SLC25A28 2.22 0.000 1267 CNP 2.22 0.000 22849 CPEB3 2.22 0.000 84333 PCGF5 2.21 0.000 7130 TNFAIP6 2.21 0.001 2635 GBP3 2.21 0.003 3824 KLRD1 2.21 0.002 23414 ZFPM2 2.21 0.003 3428 IFI16 2.21 0.000 28951 TRIB2 2.20 0.002 56911 C21orf7 2.20 0.001 9711 KIAA0226 2.20 0.000 25865 PRKD2 2.19 0.000 430 ASCL2 2.19 0.000 55785 FGD6 2.18 0.000

10737 RFPL3S 2.18 0.000 6402 SELL 2.18 0.000 64343 AZI2 2.17 0.000 27071 DAPP1 2.17 0.000 51422 PRKAG2 2.17 0.000 8797 TNFRSF10A 2.17 0.000 79570 NKAIN1 2.17 0.001 85465 SELI 2.17 0.000 375387 LRRC33 2.17 0.000 11277 TREX1 2.17 0.000 83857 TMTC1 2.17 0.016 8548 BLZF1 2.16 0.000 5819 PVRL2 2.16 0.000 56950 SMYD2 2.16 0.000 114880 OSBPL6 2.15 0.001 2820 GPD2 2.15 0.000 11011 TLK2 2.15 0.000 11044 POLS 2.14 0.000 727 C5 2.14 0.000 4502 MT2A 2.14 0.004 6539 SLC6A12 2.13 0.000 644 BLVRA 2.13 0.000 117289 TAGAP 2.13 0.000 387921 NHLRC3 2.13 0.000 55281 TMEM140 2.12 0.001 84561 SLC12A8 2.12 0.001 81844 TRIM56 2.12 0.000 3569 IL6 2.12 0.001 4683 NBN 2.11 0.000 573 BAG1 2.11 0.000 51375 SNX7 2.11 0.001 5638 PRRG1 2.11 0.000 5920 RARRES3 2.11 0.002 54020 SLC37A1 2.11 0.000 1588 CYP19A1 2.11 0.006 57130 ATP13A1 2.11 0.000 27350 APOBEC3C 2.11 0.000 10589 DRAP1 2.11 0.000 154141 MBOAT1 2.11 0.000 8676 STX11 2.10 0.000 56987 BBX 2.10 0.000 57153 SLC44A2 2.10 0.000 135114 HINT3 2.10 0.000 5464 PPA1 2.10 0.000 54464 XRN1 2.09 0.000 84248 FYTTD1 2.09 0.000 10906 TRAFD1 2.09 0.000 3290 HSD11B1 2.09 0.001 9111 NMI 2.09 0.000 4493 MT1E 2.09 0.000 7286 TUFT1 2.08 0.000 10475 TRIM38 2.08 0.000

64761 PARP12 2.08 0.000 126321 C19orf28 2.08 0.000 6654 SOS1 2.08 0.000 253782 LASS6 2.07 0.000 159013 CXorf38 2.07 0.000 3673 ITGA2 2.06 0.001 391020 LOC391020 2.06 0.000 79827 ASAM 2.05 0.001 30844 EHD4 2.05 0.000 387751 GVIN1 2.05 0.003 3112 HLA-DOB 2.05 0.002 7082 TJP1 2.04 0.000 26509 MYOF 2.04 0.000 127396 ZNF684 2.04 0.000 92797 HELB 2.04 0.001 215 ABCD1 2.03 0.000 6715 SRD5A1 2.03 0.000 166379 BBS12 2.03 0.000 9915 ARNT2 2.03 0.016 93349 SP140L 2.02 0.000 84102 SLC41A2 2.02 0.000 51309 ARMCX1 2.01 0.000 9399 STOML1 2.01 0.000 55689 YEATS2 2.01 0.000 84162 KIAA1109 2.01 0.000 54988 ACSM5 2.01 0.002 153684 LOC153684 2.01 0.000 5763 PTMS 2.01 0.001 6948 TCN2 2.01 0.000 57706 DENND1A 2.01 0.000 2132 EXT2 2.01 0.000 84955 NUDCD1 2.00 0.000 4144 MAT2A 2.00 0.001 306 ANXA3 2.00 0.016 5696 PSMB8 2.00 0.000 3575 IL7R 2.00 0.002 57674 RNF213 1.99 0.000 8464 SUPT3H 1.99 0.000 25932 CLIC4 1.99 0.000 2235 FECH 1.99 0.000 23064 SETX 1.99 0.000 25939 SAMHD1 1.99 0.002 5129 PCTK3 1.98 0.002 3304 HSPA1B 1.98 0.000 25861 DFNB31 1.98 0.000 55013 CCDC109B 1.98 0.000 5366 PMAIP1 1.97 0.000 84142 FAM175A 1.97 0.000 154214 RNF217 1.97 0.000 716 C1S 1.97 0.004 23607 CD2AP 1.97 0.000 4299 AFF1 1.96 0.000

2185 PTK2B 1.96 0.000 195827 C9orf21 1.96 0.000 5414 SEPT4 1.96 0.002 2015 EMR1 1.96 0.013 836 CASP3 1.95 0.000 7072 TIA1 1.95 0.000 83642 RP3-402G11.5 1.95 0.000 7430 EZR 1.95 0.000 2180 ACSL1 1.94 0.000 51439 FAM8A1 1.94 0.001 80176 SPSB1 1.94 0.005 83854 ANGPTL6 1.94 0.001 153222 C5orf41 1.94 0.001 5899 RALB 1.94 0.000 11024 LILRA1 1.94 0.001 113277 TMEM106A 1.94 0.000 3002 GZMB 1.94 0.002 145567 TTC7B 1.93 0.000 8737 RIPK1 1.93 0.000 7726 TRIM26 1.93 0.000 715 C1R 1.93 0.003 51314 TXNDC3 1.93 0.003 4067 LYN 1.93 0.000 1573 CYP2J2 1.93 0.000 838 CASP5 1.93 0.001 121441 NEDD1 1.93 0.000 83990 BRIP1 1.92 0.018 2012 EMP1 1.92 0.000 342035 GLDN 1.92 0.004 55020 TTC38 1.92 0.000 5393 EXOSC9 1.92 0.000 11179 ZNF277 1.92 0.000 57486 NLN 1.92 0.000 63916 ELMO2 1.92 0.000 688 KLF5 1.92 0.001 6741 SSB 1.92 0.000 23165 NUP205 1.92 0.000 246329 STAC3 1.91 0.000 115362 GBP5 1.91 0.020 5142 PDE4B 1.91 0.001 6314 ATXN7 1.91 0.001 57590 WDFY1 1.91 0.000 246778 IL27 1.91 0.000 54625 PARP14 1.90 0.000 994 CDC25B 1.90 0.000 4205 MEF2A 1.90 0.000 961 CD47 1.90 0.000 6993 DYNLT1 1.90 0.000 2175 FANCA 1.89 0.000 10392 NOD1 1.89 0.000 54936 ADPRHL2 1.89 0.000 356 FASLG 1.89 0.006

51316 PLAC8 1.89 0.001 26060 APPL1 1.89 0.000 63875 MRPL17 1.89 0.000 11177 BAZ1A 1.89 0.000 28778 IGLV6-57 1.88 0.014 91351 DDX60L 1.88 0.000 79657 RPAP3 1.88 0.000 8651 SOCS1 1.88 0.001 8987 STBD1 1.88 0.000 4210 MEFV 1.88 0.001 6737 TRIM21 1.88 0.000 AFFX- #N/A 1.88 0.012 HUMISGF3A/M97935_5 4534 MTM1 1.88 0.000 57061 HYMAI 1.88 0.002 4088 SMAD3 1.88 0.000 197259 MLKL 1.87 0.002 8291 DYSF 1.87 0.001 222255 ATXN7L1 1.87 0.000 51056 LAP3 1.87 0.001 5732 PTGER2 1.87 0.000 253260 RICTOR 1.86 0.000 256586 LYSMD2 1.86 0.000 5155 PDGFB 1.86 0.000 91056 DKFZp761E198 1.85 0.001 167153 PAPD4 1.85 0.000 55835 CENPJ 1.85 0.000 118932 ANKRD22 1.85 0.027 11006 LILRB4 1.85 0.000 5613 PRKX 1.85 0.000 9961 MVP 1.85 0.000 5586 PKN2 1.84 0.002 23279 NUP160 1.84 0.000 163486 DENND1B 1.84 0.002 10943 MSL3 1.84 0.000 24147 FJX1 1.84 0.001 54676 GTPBP2 1.84 0.000 5334 PLCL1 1.84 0.000 9693 RAPGEF2 1.84 0.000 9725 TMEM63A 1.84 0.000 80021 TMEM62 1.83 0.000 130589 GALM 1.83 0.000 338339 CLEC4D 1.83 0.000 56259 CTNNBL1 1.83 0.000 8303 SNN 1.83 0.000 387032 ZKSCAN4 1.83 0.000 25923 ATL3 1.83 0.000 9805 SCRN1 1.83 0.001 54979 HRASLS2 1.83 0.000 2191 FAP 1.82 0.036 9014 TAF1B 1.82 0.000 6453 ITSN1 1.82 0.000

148932 MOBKL2C 1.81 0.000 5152 PDE9A 1.81 0.041 9833 MELK 1.81 0.002 5214 PFKP 1.81 0.000 5937 RBMS1 1.81 0.000 389073 C2orf80 1.81 0.008 1466 CSRP2 1.81 0.001 151195 CCNYL1 1.80 0.000 6363 CCL19 1.80 0.001 83439 TCF7L1 1.80 0.006 22875 ENPP4 1.80 0.000 29760 BLNK 1.80 0.000 57489 ODF2L 1.80 0.000 4302 MLLT6 1.80 0.000 58489 FAM108C1 1.80 0.003 8837 CFLAR 1.80 0.000 6674 SPAG1 1.80 0.001 84547 PGBD1 1.80 0.000 8869 ST3GAL5 1.80 0.000 375056 MIA3 1.80 0.000 962 CD48 1.79 0.001 10644 IGF2BP2 1.79 0.001 51177 PLEKHO1 1.78 0.000 9712 USP6NL 1.78 0.000 8809 IL18R1 1.78 0.010 55577 NAGK 1.78 0.000 51510 CHMP5 1.78 0.000 51100 SH3GLB1 1.78 0.000 57194 ATP10A 1.78 0.000 55669 MFN1 1.78 0.000 221656 AOF1 1.78 0.001 7779 SLC30A1 1.78 0.000 5128 PCTK2 1.78 0.000 10678 B3GNT2 1.77 0.000 51274 KLF3 1.77 0.000 2037 EPB41L2 1.77 0.001 152007 GLIPR2 1.77 0.000 169200 TMEM64 1.77 0.002 474344 GIMAP6 1.77 0.004 27351 PPPDE2 1.77 0.000 80231 CXorf21 1.76 0.000 3344 FOXN2 1.76 0.001 23597 ACOT9 1.76 0.000 221749 C6orf145 1.76 0.001 80012 PHC3 1.76 0.000 51700 CYB5R2 1.76 0.000 54507 ADAMTSL4 1.76 0.000 5520 PPP2R2A 1.76 0.000 5150 PDE7A 1.75 0.003 147463 ANKRD29 1.75 0.012 65264 UBE2Z 1.75 0.000 54847 SIDT1 1.75 0.006

10605 PAIP1 1.74 0.000 80017 C14orf159 1.74 0.000 93185 IGSF8 1.74 0.000 5747 PTK2 1.74 0.002 8601 RGS20 1.74 0.001 11135 CDC42EP1 1.74 0.013 9381 OTOF 1.74 0.014 284004 HEXDC 1.73 0.000 51334 PRR16 1.73 0.002 79669 C3orf52 1.73 0.003 9683 N4BP1 1.73 0.000 121268 RHEBL1 1.73 0.000 4149 MAX 1.73 0.000 64398 MPP5 1.73 0.000 27185 DISC1 1.73 0.000 222161 DKFZP586I1420 1.73 0.000 5698 PSMB9 1.72 0.002 24141 C20orf103 1.72 0.018 60489 APOBEC3G 1.72 0.004 7006 TEC 1.72 0.000 201475 RAB12 1.72 0.005 5066 PAM 1.71 0.004 22902 RUFY3 1.71 0.000 3586 IL10 1.71 0.000 2634 GBP2 1.71 0.010 201456 FBXO15 1.71 0.001 7170 TPM3 1.71 0.000 10098 TSPAN5 1.71 0.003 57609 DIP2B 1.71 0.000 9252 RPS6KA5 1.71 0.002 29767 TMOD2 1.70 0.001 81796 SLCO5A1 1.70 0.002 9473 C1orf38 1.70 0.000 389 RHOC 1.70 0.001 59350 RXFP1 1.70 0.004 79668 PARP8 1.70 0.000 5524 PPP2R4 1.70 0.000 51131 PHF11 1.70 0.000 4616 GADD45B 1.70 0.000 971 CD72 1.70 0.001 4121 MAN1A1 1.70 0.000 84335 AKT1S1 1.69 0.003 9934 P2RY14 1.69 0.013 1992 SERPINB1 1.69 0.000 64215 DNAJC1 1.69 0.000 6773 STAT2 1.69 0.000 8454 CUL1 1.68 0.000 2651 GCNT2 1.68 0.000 646561 LOC646561 1.68 0.001 10875 FGL2 1.68 0.002 6890 TAP1 1.68 0.003 4082 MARCKS 1.68 0.000

5875 RABGGTA 1.68 0.000 51760 SYT17 1.68 0.003 9610 RIN1 1.68 0.001 273 AMPH 1.68 0.013 22978 NT5C2 1.68 0.000 221421 RSPH9 1.67 0.004 165324 UBXN2A 1.67 0.000 51092 SIDT2 1.67 0.000 7262 PHLDA2 1.67 0.004 1540 CYLD 1.67 0.001 26750 RPS6KC1 1.67 0.000 84225 ZMYND15 1.67 0.012 51762 RAB8B 1.67 0.000 23623 RUSC1 1.66 0.000 59274 MESDC1 1.66 0.001 80351 TNKS2 1.66 0.001 8418 CMAH 1.66 0.008 8573 CASK 1.66 0.000 10379 IRF9 1.66 0.001 64218 SEMA4A 1.66 0.000 578 BAK1 1.66 0.001 115825 WDFY2 1.66 0.001 94134 ARHGAP12 1.66 0.000 5325 PLAGL1 1.65 0.001 26157 GIMAP2 1.65 0.001 58533 SNX6 1.65 0.000 9079 LDB2 1.65 0.048 6641 SNTB1 1.65 0.000 2621 GAS6 1.65 0.001 83547 RILP 1.65 0.000 141 ADPRH 1.65 0.001 3099 HK2 1.65 0.000 4277 MICB 1.65 0.000 28773 IGLV9-49 1.65 0.020 3001 GZMA 1.65 0.001 27074 LAMP3 1.65 0.002 10123 ARL4C 1.64 0.000 55234 SMU1 1.64 0.000 643314 KIAA0754 1.64 0.002 3660 IRF2 1.64 0.000 8717 TRADD 1.64 0.001 7402 UTRN 1.64 0.001 1140 CHRNB1 1.64 0.001 10903 MTMR11 1.64 0.001 2618 GART 1.64 0.001 1390 CREM 1.64 0.000 64167 ERAP2 1.64 0.004 26037 SIPA1L1 1.64 0.003 1666 DECR1 1.64 0.000 57699 CPNE5 1.64 0.027 1235 CCR6 1.64 0.001 11054 OGFR 1.64 0.000

23780 APOL2 1.64 0.001 10186 LHFP 1.64 0.000 2040 STOM 1.64 0.000 1075 CTSC 1.63 0.000 79577 CDC73 1.63 0.000 10581 IFITM2 1.63 0.001 2530 FUT8 1.63 0.002 54947 LPCAT2 1.63 0.001 3045 HBD 1.63 0.010 50650 ARHGEF3 1.63 0.001 10241 CALCOCO2 1.63 0.000 4615 MYD88 1.63 0.000 23786 BCL2L13 1.63 0.000 5655 KLK10 1.63 0.008 5699 PSMB10 1.63 0.001 54149 C21orf91 1.63 0.002 7290 HIRA 1.63 0.000 116496 FAM129A 1.63 0.012 608 TNFRSF17 1.62 0.001 9672 SDC3 1.62 0.006 57613 KIAA1467 1.62 0.000 55770 EXOC2 1.62 0.000 57419 SLC24A3 1.62 0.005 143630 UBQLNL 1.62 0.000 55072 RNF31 1.61 0.000 9592 IER2 1.61 0.001 5883 RAD9A 1.61 0.000 51471 NAT8B 1.61 0.002 1636 ACE 1.61 0.000 1906 EDN1 1.61 0.007 29071 C1GALT1C1 1.61 0.000 23224 SYNE2 1.61 0.004 80173 IFT74 1.61 0.001 80237 ELL3 1.61 0.000 9641 IKBKE 1.61 0.000 81537 SGPP1 1.61 0.000 3140 MR1 1.61 0.000 AFFX-M27830_5 #N/A 1.61 0.020 9958 USP15 1.60 0.000 7444 VRK2 1.60 0.001 146857 SLFN13 1.60 0.003 85440 DOCK7 1.60 0.000 5683 PSMA2 1.60 0.000 23177 CEP68 1.60 0.001 84808 C1orf170 1.60 0.000 2332 FMR1 1.60 0.000 3667 IRS1 1.60 0.036 4192 MDK 1.60 0.003 6533 SLC6A6 1.60 0.003 717 C2 1.60 0.018 9267 CYTH1 1.60 0.000 1608 DGKG 1.60 0.001

5891 RAGE 1.59 0.009 4124 MAN2A1 1.59 0.006 9373 PLAA 1.59 0.000 2005 ELK4 1.59 0.001 401494 PTPLAD2 1.59 0.000 51444 RNF138 1.59 0.000 56942 C16orf61 1.59 0.000 79651 RHBDF2 1.59 0.001 64127 NOD2 1.59 0.001 51237 MGC29506 1.59 0.002 7405 UVRAG 1.59 0.000 64005 MYO1G 1.58 0.000 11176 BAZ2A 1.58 0.000 64282 PAPD5 1.58 0.001 114822 RHPN1 1.58 0.000 8204 NRIP1 1.58 0.000 5627 PROS1 1.58 0.001 4117 MAK 1.58 0.007 55303 GIMAP4 1.58 0.012 92745 SLC38A5 1.57 0.001 51299 NRN1 1.57 0.016 118429 ANTXR2 1.57 0.000 142686 ASB14 1.57 0.004 834 CASP1 1.57 0.000 139322 APOOL 1.57 0.000 160365 CLECL1 1.57 0.003 399 RHOH 1.57 0.000 388335 TMEM220 1.57 0.001 60485 SAV1 1.57 0.000 53917 RAB24 1.57 0.001 51393 TRPV2 1.57 0.001 55964 SEPT3 1.57 0.024 28825 IGLV1-40 1.57 0.001 11035 RIPK3 1.57 0.000 411 ARSB 1.57 0.000 113829 SLC35A4 1.56 0.000 63899 NSUN3 1.56 0.000 10567 RABAC1 1.56 0.000 55114 ARHGAP17 1.56 0.000 116984 ARAP2 1.56 0.007 3937 LCP2 1.56 0.004 63898 SH2D4A 1.56 0.002 144423 GLT1D1 1.56 0.001 2841 GPR18 1.56 0.006 987 LRBA 1.56 0.001 51054 PLEKHA9 1.56 0.004 54467 ANKIB1 1.56 0.000 8760 CDS2 1.56 0.002 950 SCARB2 1.55 0.000 11165 NUDT3 1.55 0.001 2069 EREG 1.55 0.018 9814 SFI1 1.55 0.001

9124 PDLIM1 1.55 0.001 28797 IGLV3-19 1.55 0.014 10010 TANK 1.55 0.002 5795 PTPRJ 1.55 0.012 64327 LMBR1 1.55 0.003 124446 TMEM219 1.55 0.000 51365 PLA1A 1.55 0.000 51466 EVL 1.55 0.000 25934 NIPSNAP3A 1.54 0.000 646329 hCG_2038586 1.54 0.003 64689 GORASP1 1.54 0.000 2787 GNG5 1.54 0.000 9334 B4GALT5 1.54 0.000 6774 STAT3 1.54 0.001 91452 ACBD5 1.54 0.000 729806 LOC729806 1.54 0.031 81857 MED25 1.54 0.001 5341 PLEK 1.54 0.000 9969 MED13 1.54 0.001 55236 UBA6 1.54 0.000 30009 TBX21 1.54 0.020 3570 IL6R 1.53 0.000 223082 ZNRF2 1.53 0.000 831 CAST 1.53 0.000 3301 DNAJA1 1.53 0.000 331 XIAP 1.53 0.000 6788 STK3 1.53 0.000 57664 PLEKHA4 1.53 0.001 669 BPGM 1.53 0.003 3003 GZMK 1.53 0.008 92906 HNRPLL 1.53 0.000 10865 ARID5A 1.53 0.000 5321 PLA2G4A 1.53 0.000 79666 PLEKHF2 1.53 0.000 9871 SEC24D 1.53 0.000 10974 C10orf116 1.52 0.002 5996 RGS1 1.52 0.002 65983 GRAMD3 1.52 0.001 645745 MT1P2 1.52 0.000 1594 CYP27B1 1.52 0.002 3512 IGJ 1.52 0.007 157983 C9orf66 1.52 0.024 400236 LOC400236 1.52 0.000 26053 AUTS2 1.52 0.001 3964 LGALS8 1.52 0.000 473 RERE 1.52 0.000 285237 C3orf38 1.52 0.001 1960 EGR3 1.52 0.006 440836 ODF3B 1.52 0.004 6478 SIAH2 1.51 0.000 389119 C3orf54 1.51 0.000 51284 TLR7 1.51 0.008

140739 UBE2F 1.51 0.001 11332 ACOT7 1.51 0.001 127018 LYPLAL1 0.66 0.001 116151 C20orf108 0.66 0.001 353116 RILPL1 0.66 0.004 84217 ZMYND12 0.66 0.005 57666 FBRSL1 0.66 0.000 1407 CRY1 0.66 0.002 23729 SHPK 0.66 0.001 863 CBFA2T3 0.66 0.006 23093 TTLL5 0.66 0.000 51 ACOX1 0.66 0.000 126074 C19orf39 0.66 0.000 26191 PTPN22 0.66 0.000 5016 OVGP1 0.66 0.002 122622 ADSSL1 0.66 0.003 883 CCBL1 0.66 0.000 286205 SCAI 0.66 0.000 128439 SNHG11 0.66 0.001 84329 HVCN1 0.66 0.003 221143 N6AMT2 0.66 0.000 221692 PHACTR1 0.66 0.001 3064 HTT 0.66 0.001 127700 OSCP1 0.66 0.004 9497 SLC4A7 0.66 0.000 10044 SH2D3C 0.66 0.000 55572 FOXRED1 0.66 0.000 55812 SPATA7 0.66 0.007 4291 MLF1 0.66 0.002 3104 ZBTB48 0.66 0.000 55902 ACSS2 0.66 0.001 60314 C12orf10 0.66 0.000 6733 SRPK2 0.66 0.000 8805 TRIM24 0.66 0.001 9788 MTSS1 0.66 0.000 11169 WDHD1 0.66 0.000 9984 THOC1 0.66 0.000 55556 ENOSF1 0.66 0.000 124402 FAM100A 0.66 0.000 57143 ADCK1 0.66 0.001 25911 RP11-529I10.4 0.66 0.004 23513 SCRIB 0.66 0.001 23768 FLRT2 0.66 0.000 27175 TUBG2 0.66 0.001 23613 ZMYND8 0.66 0.000 97 ACYP1 0.66 0.000 414919 C8orf82 0.66 0.001 9060 PAPSS2 0.66 0.000 114327 EFHC1 0.66 0.001 84968 PNMA6A 0.66 0.001 79411 GLB1L 0.66 0.001 157506 RDH10 0.66 0.000

1787 TRDMT1 0.65 0.000 84223 IQCG 0.65 0.000 1797 DOM3Z 0.65 0.000 2288 FKBP4 0.65 0.000 25809 TTLL1 0.65 0.000 81706 PPP1R14C 0.65 0.004 23461 ABCA5 0.65 0.000 79675 FASTKD1 0.65 0.000 2218 FKTN 0.65 0.001 55260 TMEM143 0.65 0.003 84657 C3orf42 0.65 0.002 4048 LTA4H 0.65 0.000 5836 PYGL 0.65 0.000 7556 ZNF10 0.65 0.001 55508 SLC35E3 0.65 0.000 9706 ULK2 0.65 0.001 55713 ZNF334 0.65 0.006 54985 HCFC1R1 0.65 0.000 729220 FLJ45513 0.65 0.001 1 A1BG 0.65 0.001 54762 GRAMD1C 0.65 0.001 51537 MTP18 0.65 0.000 7639 ZNF85 0.65 0.004 85302 FBF1 0.65 0.000 90203 SNX21 0.65 0.001 10873 ME3 0.65 0.003 1955 MEGF9 0.65 0.001 90874 ZNF697 0.65 0.000 84105 PCBD2 0.65 0.000 116841 SNAP47 0.65 0.000 220323 OAF 0.65 0.000 64981 MRPL34 0.65 0.001 121457 IKIP 0.65 0.001 1728 NQO1 0.65 0.000 8082 SSPN 0.65 0.008 54920 DUS2L 0.65 0.000 9581 PREPL 0.65 0.001 8218 CLTCL1 0.65 0.001 643988 LOC643988 0.65 0.000 8324 FZD7 0.65 0.001 842 CASP9 0.65 0.001 201514 ZNF584 0.65 0.000 10946 SF3A3 0.65 0.000 10682 EBP 0.65 0.001 51157 ZNF580 0.65 0.002 4913 NTHL1 0.65 0.002 1104 RCC1 0.65 0.001 619435 C8orf61 0.65 0.001 261734 NPHP4 0.65 0.000 64858 DCLRE1B 0.65 0.001 149076 ZNF362 0.65 0.000 10321 CRISP3 0.65 0.014

29954 POMT2 0.65 0.000 117155 CATSPER2 0.65 0.002 5378 PMS1 0.65 0.001 84080 C16orf48 0.65 0.000 81888 HYI 0.65 0.001 6621 SNAPC4 0.65 0.000 26517 TIMM13 0.65 0.000 1809 DPYSL3 0.65 0.002 3614 IMPDH1 0.65 0.000 29780 PARVB 0.65 0.000 79644 SRD5A3 0.65 0.001 117144 CATSPER1 0.65 0.005 753 C18orf1 0.65 0.002 24142 NAT6 0.65 0.000 150483 TEKT4 0.65 0.001 79850 FAM57A 0.65 0.000 253558 LCLAT1 0.64 0.001 9650 MTFR1 0.64 0.000 286262 C9orf75 0.64 0.000 9371 KIF3B 0.64 0.000 7227 TRPS1 0.64 0.001 728537 LOC728537 0.64 0.018 5190 PEX6 0.64 0.001 57460 PPM1H 0.64 0.000 5261 PHKG2 0.64 0.000 5425 POLD2 0.64 0.000 27433 TOR2A 0.64 0.000 51449 PCYOX1 0.64 0.001 4832 NME3 0.64 0.000 5198 PFAS 0.64 0.001 27005 USP21 0.64 0.000 63920 C5orf54 0.64 0.006 22838 RNF44 0.64 0.002 58476 TP53INP2 0.64 0.002 8518 IKBKAP 0.64 0.001 55655 NLRP2 0.64 0.003 50626 CYHR1 0.64 0.001 6519 SLC3A1 0.64 0.024 27300 ZNF544 0.64 0.001 390595 LOC390595 0.64 0.001 2166 FAAH 0.64 0.001 2067 ERCC1 0.64 0.000 54841 BIVM 0.64 0.000 9677 HISPPD2A 0.64 0.000 285362 SUMF1 0.64 0.000 3858 KRT10 0.64 0.001 6659 SOX4 0.64 0.001 55 ACPP 0.64 0.014 57089 ENTPD7 0.64 0.000 55274 PHF10 0.64 0.001 81490 PTDSS2 0.64 0.000 6566 SLC16A1 0.64 0.001

57533 TBC1D14 0.64 0.000 79064 TMEM223 0.64 0.000 200958 MUC20 0.64 0.002 51256 TBC1D7 0.64 0.001 5176 SERPINF1 0.64 0.004 84936 ZFYVE19 0.64 0.000 9920 KBTBD11 0.64 0.000 23031 MAST3 0.64 0.000 23171 GPD1L 0.64 0.000 23158 TBC1D9 0.64 0.001 1718 DHCR24 0.64 0.001 55351 STK32B 0.64 0.000 144193 AMDHD1 0.64 0.001 56912 C11orf60 0.64 0.001 57679 ALS2 0.64 0.000 120227 CYP2R1 0.64 0.000 51657 STYXL1 0.64 0.000 5264 PHYH 0.64 0.000 90362 FAM110B 0.63 0.002 2974 GUCY1B2 0.63 0.018 10160 FARP1 0.63 0.000 10512 SEMA3C 0.63 0.001 10994 ILVBL 0.63 0.000 10871 CD300C 0.63 0.000 81562 LMAN2L 0.63 0.000 55244 SLC47A1 0.63 0.003 219854 TMEM218 0.63 0.000 23251 KIAA1024 0.63 0.000 645638 LOC645638 0.63 0.002 91647 ATPAF2 0.63 0.000 28986 MAGEH1 0.63 0.001 8681 JMJD7-PLA2G4B 0.63 0.000 9856 KIAA0319 0.63 0.006 10509 SEMA4B 0.63 0.000 10422 UBAC1 0.63 0.000 83544 DNAL1 0.63 0.001 7267 TTC3 0.63 0.000 8544 PIR 0.63 0.000 91947 ARRDC4 0.63 0.001 84803 AGPAT9 0.63 0.000 91355 LRP5L 0.63 0.002 84912 SLC35B4 0.63 0.000 26147 PHF19 0.63 0.000 64147 KIF9 0.63 0.001 9454 HOMER3 0.63 0.002 57189 KIAA1147 0.63 0.000 84216 TMEM117 0.63 0.000 2030 SLC29A1 0.63 0.001 79718 TBL1XR1 0.63 0.001 25973 PARS2 0.63 0.000 197320 ZNF778 0.63 0.002 92960 PEX11G 0.63 0.000

89849 ATG16L2 0.63 0.000 126364 LRRC25 0.63 0.000 23239 PHLPP1 0.63 0.001 5654 HTRA1 0.63 0.000 3373 HYAL1 0.63 0.000 57658 CALCOCO1 0.63 0.000 23413 FREQ 0.63 0.002 4199 ME1 0.63 0.004 9653 HS2ST1 0.63 0.000 5595 MAPK3 0.63 0.000 64772 ENGASE 0.63 0.000 130888 FBXO36 0.63 0.002 124961 ZFP3 0.63 0.000 8853 ASAP2 0.63 0.000 10244 RABEPK 0.63 0.000 1012 CDH13 0.63 0.000 4860 NP 0.63 0.000 149421 C1orf215 0.63 0.001 147965 FAM98C 0.62 0.000 5116 PCNT 0.62 0.000 6526 SLC5A3 0.62 0.000 54206 ERRFI1 0.62 0.003 285550 LOC285550 0.62 0.000 489 ATP2A3 0.62 0.000 126272 EID2B 0.62 0.000 4542 MYO1F 0.62 0.000 79789 CLMN 0.62 0.001 63941 NECAB3 0.62 0.001 113802 C1orf59 0.62 0.001 22881 ANKRD6 0.62 0.001 3553 IL1B 0.62 0.001 26751 SH3YL1 0.62 0.001 144717 FAM109A 0.62 0.001 23139 MAST2 0.62 0.000 2027 ENO3 0.62 0.000 440465 FLJ90757 0.62 0.002 25886 WDR51A 0.62 0.000 8520 HAT1 0.62 0.000 84747 UNC119B 0.62 0.000 2013 EMP2 0.62 0.006 9338 TCEAL1 0.62 0.000 8604 SLC25A12 0.62 0.000 147015 DHRS13 0.62 0.001 9051 PSTPIP1 0.62 0.002 4041 LRP5 0.62 0.001 8642 DCHS1 0.62 0.002 145389 SLC38A6 0.62 0.001 5635 PRPSAP1 0.62 0.000 79958 DENND1C 0.62 0.000 26505 CNNM3 0.62 0.001 56907 SPIRE1 0.62 0.000 84291 MGC2408 0.62 0.000

6383 SDC2 0.62 0.000 4828 NMB 0.62 0.006 84898 PLXDC2 0.62 0.000 79731 NARS2 0.62 0.000 9654 TTLL4 0.62 0.000 617 BCS1L 0.62 0.000 4215 MAP3K3 0.62 0.000 388341 C17orf76 0.62 0.004 6310 ATXN1 0.62 0.000 4601 MXI1 0.62 0.000 10200 MPHOSPH6 0.62 0.000 22852 ANKRD26 0.62 0.005 4303 FOXO4 0.62 0.000 8501 SLC43A1 0.61 0.000 8829 NRP1 0.61 0.000 435 ASL 0.61 0.000 57096 RPGRIP1 0.61 0.001 64393 ZMAT3 0.61 0.007 79778 MICALL2 0.61 0.000 347744 C6orf52 0.61 0.004 10811 NOXA1 0.61 0.000 10849 CD3EAP 0.61 0.001 84309 NUDT16L1 0.61 0.000 10144 FAM13A 0.61 0.002 10277 UBE4B 0.61 0.004 27036 SIGLEC7 0.61 0.000 57580 PREX1 0.61 0.000 9772 KIAA0195 0.61 0.001 23116 FAM179B 0.61 0.000 126789 PUSL1 0.61 0.000 26974 ZNF285A 0.61 0.000 978 CDA 0.61 0.001 408 ARRB1 0.61 0.001 3386 ICAM4 0.61 0.009 94239 H2AFV 0.61 0.000 7289 TULP3 0.61 0.000 7730 ZNF177 0.61 0.002 3579 IL8RB 0.61 0.002 395 ARHGAP6 0.61 0.000 9466 IL27RA 0.61 0.000 54805 CNNM2 0.61 0.001 25888 ZNF473 0.61 0.001 90198 C19orf49 0.61 0.001 55764 IFT122 0.61 0.000 57175 CORO1B 0.61 0.000 79918 SETD6 0.61 0.000 10641 TUSC4 0.61 0.000 4608 MYBPH 0.61 0.002 4359 MPZ 0.61 0.000 60677 BRUNOL6 0.61 0.000 50624 CUZD1 0.61 0.003 131474 CHCHD4 0.61 0.000

199857 ALG14 0.61 0.000 23038 WDTC1 0.61 0.000 582 BBS1 0.61 0.000 10333 TLR6 0.61 0.001 90462 ZNF605 0.61 0.000 114928 GPRASP2 0.61 0.000 143879 KBTBD3 0.60 0.000 120425 AMICA1 0.60 0.000 25989 ULK3 0.60 0.000 8744 TNFSF9 0.60 0.001 5028 P2RY1 0.60 0.004 94097 SFXN5 0.60 0.000 4647 MYO7A 0.60 0.000 729604 LOC729604 0.60 0.000 5829 PXN 0.60 0.000 51268 PIPOX 0.60 0.000 90624 LYRM7 0.60 0.000 932 MS4A3 0.60 0.003 2628 GATM 0.60 0.006 2768 GNA12 0.60 0.000 10908 PNPLA6 0.60 0.000 57520 HECW2 0.60 0.006 2119 ETV5 0.60 0.000 51776 ZAK 0.60 0.000 136 ADORA2B 0.60 0.002 23310 NCAPD3 0.60 0.000 161779 PGBD4 0.60 0.000 84959 UBASH3B 0.60 0.000 898 CCNE1 0.60 0.000 129138 ANKRD54 0.60 0.000 9121 SLC16A5 0.60 0.000 80854 SETD7 0.60 0.000 55240 STEAP3 0.60 0.001 10300 KATNB1 0.60 0.000 8270 LAGE3 0.60 0.000 374659 HDDC3 0.60 0.000 9424 KCNK6 0.60 0.000 146225 CMTM2 0.59 0.002 137835 TMEM71 0.59 0.002 7621 ZNF70 0.59 0.000 1687 DFNA5 0.59 0.002 57406 ABHD6 0.59 0.000 8195 MKKS 0.59 0.000 2152 F3 0.59 0.001 23150 FRMD4B 0.59 0.008 29090 C18orf55 0.59 0.000 29902 C12orf24 0.59 0.001 55316 RSAD1 0.59 0.000 28512 NKIRAS1 0.59 0.000 10452 TOMM40 0.59 0.000 5816 PVALB 0.59 0.000 144110 TMEM86A 0.59 0.002

57412 AS3MT 0.59 0.003 23130 ATG2A 0.59 0.000 643641 ZNF862 0.59 0.000 114826 SMYD4 0.59 0.000 11200 CHEK2 0.59 0.000 5624 PROC 0.59 0.002 7485 WRB 0.59 0.000 283663 LOC283663 0.59 0.001 2203 FBP1 0.59 0.000 3033 HADH 0.59 0.000 8038 ADAM12 0.59 0.000 80183 C13orf18 0.59 0.001 64080 RBKS 0.59 0.001 9990 SLC12A6 0.59 0.001 84331 C16orf14 0.59 0.000 23129 PLXND1 0.59 0.000 146223 CMTM4 0.59 0.000 7074 TIAM1 0.59 0.005 283687 C15orf37 0.59 0.000 8408 ULK1 0.59 0.000 3577 IL8RA 0.59 0.003 2870 GRK6 0.59 0.000 7248 TSC1 0.58 0.000 23170 TTLL12 0.58 0.000 64333 ARHGAP9 0.58 0.000 85453 TSPYL5 0.58 0.001 51267 CLEC1A 0.58 0.018 123096 SLC25A29 0.58 0.000 51490 C9orf114 0.58 0.000 91544 UBXN11 0.58 0.000 1945 EFNA4 0.58 0.000 5827 PXMP2 0.58 0.000 55630 SLC39A4 0.58 0.001 7263 TST 0.58 0.001 51205 ACP6 0.58 0.001 8309 ACOX2 0.58 0.000 83719 YPEL3 0.58 0.000 51706 CYB5R1 0.58 0.000 23678 SGK3 0.58 0.000 55049 C19orf60 0.58 0.000 255027 MPV17L 0.58 0.001 57180 ACTR3B 0.58 0.000 54849 DEF8 0.58 0.000 3309 HSPA5 0.58 0.000 84626 KRBA1 0.58 0.001 84934 C12orf52 0.58 0.001 286495 TTC3L 0.58 0.000 55972 SLC25A40 0.58 0.000 493911 PHOSPHO2 0.58 0.001 29785 CYP2S1 0.58 0.001 4728 NDUFS8 0.58 0.000 127281 C1orf93 0.58 0.000

95 ACY1 0.58 0.000 943 TNFRSF8 0.58 0.001 26499 PLEK2 0.58 0.000 89790 SIGLEC10 0.58 0.001 10129 FRY 0.58 0.000 5095 PCCA 0.58 0.001 387923 SERP2 0.58 0.006 2239 GPC4 0.58 0.004 6709 SPTAN1 0.58 0.000 8455 ATRN 0.58 0.000 53340 SPA17 0.58 0.001 8406 SRPX 0.58 0.003 55706 TMEM48 0.58 0.000 7100 TLR5 0.58 0.002 116447 TOP1MT 0.58 0.001 3084 NRG1 0.57 0.008 3613 IMPA2 0.57 0.000 6195 RPS6KA1 0.57 0.000 5362 PLXNA2 0.57 0.004 10809 STARD10 0.57 0.000 65108 MARCKSL1 0.57 0.000 91752 ZNF804A 0.57 0.003 64748 LPPR2 0.57 0.000 2068 ERCC2 0.57 0.001 64757 MOSC1 0.57 0.000 10732 TCFL5 0.57 0.000 166012 CHST13 0.57 0.000 93058 COQ10A 0.57 0.000 5498 PPOX 0.57 0.000 57678 GPAM 0.57 0.000 4900 NRGN 0.57 0.003 64847 SPATA20 0.57 0.001 9647 PPM1F 0.57 0.000 29904 EEF2K 0.57 0.000 2805 GOT1 0.57 0.000 9645 MICAL2 0.57 0.000 84148 MYST1 0.57 0.000 155066 ATP6V0E2 0.57 0.000 7058 THBS2 0.57 0.002 83876 MRO 0.57 0.001 90025 UBE2CBP 0.57 0.001 23355 VPS8 0.57 0.000 54806 AHI1 0.57 0.000 65258 MPPE1 0.57 0.000 53346 TM6SF1 0.57 0.000 7371 UCK2 0.57 0.001 5351 PLOD1 0.57 0.000 5452 POU2F2 0.57 0.000 7840 ALMS1 0.57 0.000 79754 ASB13 0.57 0.000 1894 ECT2 0.57 0.001 3693 ITGB5 0.57 0.000

92104 TTC30A 0.57 0.001 89891 WDR34 0.56 0.000 8714 ABCC3 0.56 0.000 79629 OCEL1 0.56 0.000 79149 ZSCAN5A 0.56 0.000 27244 SESN1 0.56 0.002 23046 KIF21B 0.56 0.001 80235 PIGZ 0.56 0.000 6447 SCG5 0.56 0.031 200765 TIGD1 0.56 0.005 9185 REPS2 0.56 0.002 285989 ZNF789 0.56 0.001 83667 SESN2 0.56 0.000 202243 CCDC125 0.56 0.000 26123 TCTN3 0.56 0.000 123016 TTC8 0.56 0.000 26027 ACOT11 0.56 0.000 7466 WFS1 0.56 0.001 729083 LOC729083 0.56 0.002 4815 NINJ2 0.56 0.000 26035 GLCE 0.56 0.000 1465 CSRP1 0.56 0.000 5864 RAB3A 0.56 0.001 51665 ASB1 0.55 0.000 64174 DPEP2 0.55 0.000 7414 VCL 0.55 0.000 146712 B3GNTL1 0.55 0.000 57728 WDR19 0.55 0.000 55116 TMEM39B 0.55 0.000 90594 ZNF439 0.55 0.002 11138 TBC1D8 0.55 0.000 57519 STARD9 0.55 0.000 2675 GFRA2 0.55 0.001 23654 PLXNB2 0.55 0.000 84892 C3orf39 0.55 0.001 4122 MAN2A2 0.55 0.000 51313 C4orf18 0.55 0.000 7084 TK2 0.55 0.000 1020 CDK5 0.55 0.001 64785 GINS3 0.55 0.000 6385 SDC4 0.55 0.000 55759 WDR12 0.55 0.000 23060 ZNF609 0.55 0.000 6916 TBXAS1 0.55 0.000 3915 LAMC1 0.55 0.000 24149 ZNF318 0.54 0.000 140710 C20orf117 0.54 0.003 54209 TREM2 0.54 0.000 64110 MAGEF1 0.54 0.000 2051 EPHB6 0.54 0.000 10633 RASL10A 0.54 0.000 549 AUH 0.54 0.001

7504 XK 0.54 0.001 3655 ITGA6 0.54 0.008 7461 CLIP2 0.54 0.000 27148 STK36 0.54 0.000 90427 BMF 0.54 0.000 54914 KIAA1797 0.54 0.000 79065 ATG9A 0.54 0.000 1645 AKR1C1 0.54 0.003 440104 LOC440104 0.54 0.000 9670 IPO13 0.54 0.000 50856 CLEC4A 0.54 0.000 89796 NAV1 0.54 0.001 275 AMT 0.54 0.000 153770 PLAC8L1 0.54 0.002 6692 SPINT1 0.54 0.000 9832 JAKMIP2 0.54 0.002 818 CAMK2G 0.54 0.000 6285 S100B 0.53 0.000 83716 CRISPLD2 0.53 0.002 10638 SPHAR 0.53 0.000 284023 LOC284023 0.53 0.000 91433 RCCD1 0.53 0.000 84679 SLC9A7 0.53 0.000 64101 LRRC4 0.53 0.000 90835 C16orf93 0.53 0.001 80823 BHLHB9 0.53 0.005 26207 PITPNC1 0.53 0.000 55857 C20orf19 0.53 0.000 91768 CABLES1 0.53 0.001 5742 PTGS1 0.53 0.000 375757 C9orf119 0.53 0.000 27141 CIDEB 0.53 0.000 50862 RNF141 0.53 0.000 57007 CXCR7 0.53 0.006 5029 P2RY2 0.53 0.000 64170 CARD9 0.53 0.000 114134 SLC2A13 0.52 0.000 83953 FCAMR 0.52 0.001 3914 LAMB3 0.52 0.000 353324 SPATA12 0.52 0.014 9649 RALGPS1 0.52 0.002 124637 CYB5D1 0.52 0.000 23635 SSBP2 0.52 0.000 2026 ENO2 0.52 0.000 2021 ENDOG 0.52 0.000 4013 VWA5A 0.52 0.001 54997 TESC 0.52 0.000 57209 ZNF248 0.52 0.000 352954 GATS 0.52 0.000 152002 C3orf21 0.52 0.000 27347 STK39 0.52 0.000 7593 MZF1 0.52 0.001

91419 XRCC6BP1 0.52 0.000 11057 ABHD2 0.52 0.000 132 ADK 0.52 0.000 63874 ABHD4 0.52 0.000 4854 NOTCH3 0.52 0.001 122970 ACOT4 0.52 0.001 27287 VENTX 0.52 0.000 29901 SAC3D1 0.52 0.000 266655 NCRNA00094 0.52 0.000 8437 RASAL1 0.51 0.000 23555 TSPAN15 0.51 0.001 79622 SNRNP25 0.51 0.000 25959 KANK2 0.51 0.000 84913 ATOH8 0.51 0.001 54585 LZTFL1 0.51 0.000 23316 CUX2 0.51 0.002 5091 PC 0.51 0.000 728997 LOC728997 0.51 0.006 51540 SCLY 0.51 0.000 400566 C17orf97 0.51 0.001 23492 CBX7 0.51 0.000 27346 TMEM97 0.51 0.001 4774 NFIA 0.51 0.006 3145 HMBS 0.51 0.000 79153 GDPD3 0.51 0.001 26523 EIF2C1 0.51 0.000 80194 TMEM134 0.51 0.001 65018 PINK1 0.51 0.000 130162 C2orf63 0.50 0.000 6584 SLC22A5 0.50 0.000 79083 MLPH 0.50 0.004 57161 PELI2 0.50 0.000 9956 HS3ST2 0.50 0.000 56998 CTNNBIP1 0.50 0.000 400916 CHCHD10 0.50 0.000 4053 LTBP2 0.50 0.000 8100 IFT88 0.50 0.000 26115 TANC2 0.50 0.000 55703 POLR3B 0.50 0.001 340205 TREML1 0.50 0.000 50488 MINK1 0.50 0.000 23329 TBC1D30 0.50 0.001 1978 EIF4EBP1 0.50 0.000 593 BCKDHA 0.50 0.000 83742 MARVELD1 0.50 0.000 5863 RGL2 0.50 0.000 6790 AURKA 0.50 0.000 54681 P4HTM 0.49 0.000 9398 IGSF2 0.49 0.000 27239 GPR162 0.49 0.000 84795 PYROXD2 0.49 0.000 378708 APITD1 0.49 0.000

80746 TSEN2 0.49 0.000 22846 VASH1 0.49 0.000 56977 STOX2 0.49 0.006 283537 SLC46A3 0.49 0.000 81928 CABLES2 0.49 0.000 9644 SH3PXD2A 0.49 0.002 8876 VNN1 0.49 0.000 401052 LOC401052 0.48 0.000 134957 STXBP5 0.48 0.000 2242 FES 0.48 0.000 3034 HAL 0.48 0.001 586 BCAT1 0.48 0.000 245972 ATP6V0D2 0.48 0.002 51085 MLXIPL 0.47 0.000 6548 SLC9A1 0.47 0.000 9586 CREB5 0.47 0.002 113235 SLC46A1 0.47 0.002 401209 FLJ44796 0.47 0.010 146547 PRSS36 0.47 0.001 26231 LRRC29 0.47 0.001 3092 HIP1 0.47 0.000 201161 CENPV 0.47 0.000 5287 PIK3C2B 0.47 0.002 55022 PID1 0.47 0.000 6812 STXBP1 0.46 0.000 219699 UNC5B 0.46 0.002 64798 DEPDC6 0.46 0.003 6764 ST5 0.46 0.001 18 ABAT 0.46 0.000 376497 SLC27A1 0.46 0.000 2 A2M 0.46 0.002 51186 WBP5 0.46 0.000 23657 SLC7A11 0.46 0.000 26160 IFT172 0.46 0.000 8497 PPFIA4 0.45 0.002 2329 FMO4 0.45 0.001 11041 B3GNT1 0.45 0.000 91614 DEPDC7 0.45 0.000 65124 ANKRD57 0.45 0.000 29109 FHOD1 0.45 0.000 120224 TMEM45B 0.45 0.002 4128 MAOA 0.45 0.001 9705 ST18 0.45 0.006 5023 P2RX1 0.45 0.000 23022 PALLD 0.44 0.002 93589 CACNA2D4 0.44 0.000 84649 DGAT2 0.44 0.000 26064 RAI14 0.44 0.001 5467 PPARD 0.44 0.000 1306 COL15A1 0.44 0.001 284756 C20orf197 0.44 0.003 51385 ZNF589 0.44 0.000

2170 FABP3 0.43 0.000 10057 ABCC5 0.43 0.000 22918 CD93 0.43 0.000 3552 IL1A 0.43 0.001 29842 TFCP2L1 0.43 0.003 90378 SAMD1 0.43 0.000 23648 SSBP3 0.43 0.000 199675 C19orf59 0.43 0.000 3772 KCNJ15 0.43 0.000 8536 CAMK1 0.43 0.000 1474 CST6 0.43 0.001 23243 ANKRD28 0.43 0.000 285368 PRRT3 0.42 0.000 1368 CPM 0.42 0.000 121506 ERP27 0.42 0.000 64411 ARAP3 0.42 0.000 54796 BNC2 0.42 0.003 79639 TMEM53 0.42 0.000 56034 PDGFC 0.42 0.000 164091 PAQR7 0.42 0.000 83449 PMFBP1 0.42 0.000 123041 SLC24A4 0.41 0.000 202309 GAPT 0.41 0.000 6769 STAC 0.41 0.014 25927 CNRIP1 0.41 0.000 5330 PLCB2 0.41 0.000 84848 MGC16121 0.41 0.013 124599 CD300LB 0.41 0.000 54899 PXK 0.41 0.000 84279 C2orf7 0.41 0.000 440712 C1orf186 0.40 0.003 3992 FADS1 0.40 0.000 114112 TXNRD3 0.40 0.000 90627 STARD13 0.40 0.000 283876 FLJ39639 0.40 0.000 144100 PLEKHA7 0.39 0.000 7056 THBD 0.39 0.000 283316 CD163L1 0.39 0.000 338773 TMEM119 0.39 0.010 3783 KCNN4 0.39 0.000 55723 ASF1B 0.38 0.000 27345 KCNMB4 0.38 0.006 5990 RFX2 0.38 0.000 80150 ASRGL1 0.38 0.000 949 SCARB1 0.38 0.000 5980 REV3L 0.38 0.000 91662 NLRP12 0.37 0.000 284367 SIGLECP3 0.37 0.000 170591 S100Z 0.37 0.000 80741 LY6G5C 0.37 0.000 152273 FGD5 0.36 0.000 134145 FAM173B 0.36 0.000

271 AMPD2 0.36 0.000 7442 TRPV1 0.36 0.000 81035 COLEC12 0.36 0.000 23601 CLEC5A 0.36 0.001 27143 KIAA1274 0.35 0.000 388115 C15orf52 0.35 0.000 2317 FLNB 0.35 0.000 161582 DYX1C1 0.35 0.000 26577 PCOLCE2 0.34 0.001 2036 EPB41L1 0.34 0.001 84106 PRAM1 0.34 0.000 8644 AKR1C3 0.33 0.002 5738 PTGFRN 0.33 0.000 2059 EPS8 0.33 0.002 3925 STMN1 0.33 0.000 55799 CACNA2D3 0.30 0.000 116362 RBP7 0.30 0.000 80210 ARMC9 0.30 0.000 27197 GPR82 0.30 0.000 9333 TGM5 0.29 0.000 246330 PELI3 0.28 0.000 4810 NHS 0.26 0.000 23462 HEY1 0.26 0.000 5468 PPARG 0.25 0.000 29060 HSPC047 0.25 0.000 83992 CTTNBP2 0.25 0.000 4023 LPL 0.24 0.000 8460 TPST1 0.24 0.000 81501 TM7SF4 0.22 0.001 51339 DACT1 0.21 0.004 2857 GPR34 0.15 0.000

Supplementary Table VII

710 genes differentially regulated in the healthy CD133+ bone marrow EPCs treated with IFN-α compared to non-treated (q-value < 0.05).

Gene ID Gene symbol Fold-change q-value 4283 CXCL9 35.51 0.000 6373 CXCL11 23.28 0.000 6614 SIGLEC1 22.59 0.000 6357 CCL13 20.79 0.042 3429 IFI27 19.85 0.000 8638 OASL 16.17 0.000 200315 APOBEC3A 15.13 0.003 3437 IFIT3 14.27 0.000 5157 PDGFRL 12.03 0.003 116071 BATF2 11.50 0.000 3434 IFIT1 9.84 0.000 2537 IFI6 9.81 0.000 145864 HAPLN3 9.60 0.000 9636 ISG15 9.06 0.000 AFFX- #N/A 8.58 0.000 HUMISGF3A/M97935_MA 2633 GBP1 8.44 0.000 6355 CCL8 8.40 0.021 4938 OAS1 8.09 0.000 3627 CXCL10 7.97 0.010 81030 ZBP1 7.92 0.000 8519 IFITM1 7.89 0.000 1573 CYP2J2 7.87 0.000 57758 SCUBE2 7.87 0.000 51513 ETV7 7.83 0.000 118932 ANKRD22 7.80 0.021 4600 MX2 7.66 0.000 4061 LY6E 7.36 0.000 55008 HERC6 7.33 0.000 3669 ISG20 6.65 0.000 91624 NEXN 6.60 0.000 94240 EPSTI1 6.33 0.000 6354 CCL7 6.31 0.027 3430 IFI35 6.17 0.000 8900 CCNA1 6.17 0.000 4599 MX1 6.09 0.003 6398 SECTM1 6.02 0.000 162394 SLFN5 6.02 0.008 4939 OAS2 5.98 0.000 4940 OAS3 5.98 0.000 23586 DDX58 5.85 0.000 3433 IFIT2 5.67 0.000 8820 HESX1 5.44 0.000

87178 PNPT1 5.32 0.000 51191 HERC5 5.20 0.000 8743 TNFSF10 5.17 0.000 3902 LAG3 5.04 0.000 57714 KIAA1618 4.97 0.000 85441 PRIC285 4.92 0.000 629 CFB 4.84 0.000 5168 ENPP2 4.72 0.000 710 SERPING1 4.71 0.000 7098 TLR3 4.51 0.000 64108 RTP4 4.48 0.000 AFFX- #N/A 4.41 0.000 HUMISGF3A/M97935_MB 26270 FBXO6 4.24 0.000 952 CD38 4.12 0.000 91543 RSAD2 4.11 0.000 219285 SAMD9L 4.04 0.000 2766 GMPR 3.92 0.000 79132 DHX58 3.91 0.000 26010 SPATS2L 3.87 0.000 653464 SRGAP2P1 3.84 0.012 3665 IRF7 3.82 0.000 9447 AIM2 3.78 0.000 23052 ENDOD1 3.76 0.000 10964 IFI44L 3.75 0.020 26471 NUPR1 3.72 0.000 3431 SP110 3.70 0.000 3959 LGALS3BP 3.63 0.000 54739 XAF1 3.58 0.003 400941 FLJ42418 3.58 0.005 115362 GBP5 3.56 0.000 306 ANXA3 3.56 0.015 115361 GBP4 3.54 0.000 AFFX- #N/A 3.43 0.000 HUMISGF3A/M97935_5 10410 IFITM3 3.43 0.000 79570 NKAIN1 3.38 0.013 3557 IL1RN 3.37 0.024 113730 KLHDC7B 3.33 0.000 4332 MNDA 3.31 0.000 54809 SAMD9 3.25 0.000 10993 SDS 3.21 0.033 23424 TDRD7 3.12 0.000 8542 APOL1 3.11 0.000 9517 SPTLC2 3.08 0.000 7453 WARS 3.07 0.003 6891 TAP2 3.07 0.000 114793 FMNL2 3.06 0.000 80830 APOL6 3.06 0.000 80055 PGAP1 3.04 0.003 2643 GCH1 3.00 0.000 3601 IL15RA 2.97 0.003

941 CD80 2.97 0.000 83666 PARP9 2.95 0.000 84628 NTNG2 2.93 0.000 116843 C6orf192 2.89 0.000 3620 IDO1 2.88 0.022 84941 HSH2D 2.85 0.000 25939 SAMHD1 2.84 0.020 5150 PDE7A 2.83 0.000 57169 ZNFX1 2.82 0.000 26228 STAP1 2.82 0.003 23380 SRGAP2 2.80 0.000 3600 IL15 2.80 0.000 2131 EXT1 2.77 0.000 221002 RASGEF1A 2.76 0.000 3075 CFH 2.73 0.008 3112 HLA-DOB 2.73 0.000 3586 IL10 2.71 0.046 3479 IGF1 2.71 0.000 7706 TRIM25 2.70 0.000 51251 NT5C3 2.68 0.000 5420 PODXL 2.67 0.000 55601 DDX60 2.67 0.000 57593 EBF4 2.65 0.003 684 BST2 2.62 0.000 6772 STAT1 2.61 0.000 30844 EHD4 2.61 0.010 51284 TLR7 2.61 0.000 4343 MOV10 2.60 0.000 634 CEACAM1 2.60 0.003 355 FAS 2.59 0.000 26509 MYOF 2.59 0.000 84930 MASTL 2.59 0.013 10379 IRF9 2.59 0.000 9576 SPAG6 2.59 0.020 4502 MT2A 2.58 0.007 873 CBR1 2.57 0.003 6890 TAP1 2.56 0.000 137075 CLDN23 2.55 0.000 199223 TTC21A 2.55 0.000 9830 TRIM14 2.55 0.000 5371 PML 2.53 0.000 1230 CCR1 2.52 0.000 6737 TRIM21 2.52 0.000 55501 CHST12 2.51 0.000 5610 EIF2AK2 2.50 0.000 10859 LILRB1 2.49 0.022 8775 NAPA 2.48 0.000 9910 RABGAP1L 2.45 0.000 24138 IFIT5 2.45 0.009 10643 IGF2BP3 2.44 0.000 142686 ASB14 2.40 0.049 93082 NEURL3 2.39 0.045

10616 RBCK1 2.38 0.000 11277 TREX1 2.35 0.000 151556 GPR155 2.35 0.005 10561 IFI44 2.35 0.021 5698 PSMB9 2.34 0.000 2175 FANCA 2.34 0.024 55106 SLFN12 2.33 0.004 152007 GLIPR2 2.32 0.007 59345 GNB4 2.32 0.012 8548 BLZF1 2.31 0.030 57168 ASPHD2 2.31 0.020 91351 DDX60L 2.30 0.012 9683 N4BP1 2.30 0.000 4012 LNPEP 2.30 0.014 55020 TTC38 2.30 0.042 197259 MLKL 2.29 0.000 23086 EXPH5 2.29 0.042 25865 PRKD2 2.26 0.000 64762 FAM59A 2.25 0.039 64135 IFIH1 2.25 0.003 7424 VEGFC 2.25 0.011 467 ATF3 2.25 0.012 91056 DKFZp761E198 2.24 0.000 55337 C19orf66 2.24 0.000 10906 TRAFD1 2.23 0.000 9881 LBA1 2.23 0.000 159013 CXorf38 2.22 0.024 219537 SMTNL1 2.20 0.031 3965 LGALS9 2.20 0.000 23034 SAMD4A 2.19 0.020 10855 HPSE 2.19 0.014 375035 SFT2D2 2.19 0.000 159091 FAM122C 2.17 0.000 65979 PHACTR4 2.17 0.005 55281 TMEM140 2.17 0.000 160897 GPR180 2.17 0.005 51056 LAP3 2.15 0.000 729839 LOC729839 2.14 0.000 440836 ODF3B 2.14 0.000 57823 SLAMF7 2.14 0.003 9997 SCO2 2.13 0.000 23780 APOL2 2.12 0.000 10673 TNFSF13B 2.11 0.000 23070 FTSJD2 2.11 0.000 158219 TTC39B 2.10 0.027 51479 ANKFY1 2.10 0.000 7280 TUBB2A 2.09 0.000 54877 ZCCHC2 2.09 0.000 219988 PATL1 2.09 0.003 391020 LOC391020 2.09 0.000 253639 ZNF620 2.09 0.018 55300 PI4K2B 2.09 0.000

256236 NAPSB 2.08 0.006 64761 PARP12 2.08 0.000 4582 MUC1 2.07 0.003 114991 ZNF618 2.06 0.029 84875 PARP10 2.06 0.000 57097 PARP11 2.06 0.000 55509 BATF3 2.06 0.033 253018 HCG27 2.06 0.005 286334 LOC286334 2.04 0.005 5359 PLSCR1 2.03 0.000 4493 MT1E 2.03 0.013 83401 ELOVL3 2.03 0.029 10589 DRAP1 2.03 0.000 1847 DUSP5 2.02 0.034 4499 MT1M 2.01 0.003 55026 FAM70A 2.00 0.011 25825 BACE2 2.00 0.000 132321 C4orf33 1.99 0.000 152926 PPM1K 1.99 0.007 10391 CORO2B 1.99 0.005 54847 SIDT1 1.98 0.000 81894 SLC25A28 1.98 0.000 132320 SCLT1 1.97 0.000 59 ACTA2 1.97 0.000 53826 FXYD6 1.96 0.009 57674 RNF213 1.96 0.000 11006 LILRB4 1.94 0.014 85477 SCIN 1.94 0.032 84102 SLC41A2 1.94 0.013 6993 DYNLT1 1.93 0.003 81844 TRIM56 1.93 0.000 93343 FAM125A 1.92 0.003 9674 KIAA0040 1.92 0.011 246329 STAC3 1.92 0.012 8464 SUPT3H 1.91 0.000 148932 MOBKL2C 1.90 0.000 9246 UBE2L6 1.89 0.000 5800 PTPRO 1.89 0.003 10875 FGL2 1.89 0.000 54625 PARP14 1.87 0.012 259307 IL4I1 1.86 0.008 6773 STAT2 1.86 0.000 10581 IFITM2 1.86 0.000 84868 HAVCR2 1.86 0.029 719 C3AR1 1.86 0.039 51422 PRKAG2 1.85 0.000 83854 ANGPTL6 1.84 0.000 7006 TEC 1.84 0.045 7290 HIRA 1.84 0.000 9567 GTPBP1 1.84 0.027 23179 RGL1 1.84 0.008 130589 GALM 1.83 0.021

957 ENTPD5 1.83 0.027 112849 C14orf149 1.83 0.003 1267 CNP 1.82 0.000 29761 USP25 1.82 0.000 23347 SMCHD1 1.82 0.000 22809 ATF5 1.81 0.005 5899 RALB 1.80 0.034 79730 NSUN7 1.80 0.032 257019 FRMD3 1.80 0.011 5920 RARRES3 1.80 0.000 1890 TYMP 1.79 0.013 578 BAK1 1.78 0.042 5883 RAD9A 1.78 0.003 54467 ANKIB1 1.78 0.000 3717 JAK2 1.78 0.010 3728 JUP 1.78 0.008 8450 CUL4B 1.77 0.013 144165 PRICKLE1 1.77 0.021 10970 CKAP4 1.77 0.012 23273 KIAA0367 1.77 0.000 84706 GPT2 1.76 0.045 64853 AIDA 1.76 0.000 573 BAG1 1.76 0.003 659 BMPR2 1.76 0.010 147645 LOC147645 1.75 0.003 317649 EIF4E3 1.75 0.003 5696 PSMB8 1.75 0.000 79595 SAP130 1.74 0.034 116028 C16orf75 1.74 0.042 3428 IFI16 1.74 0.000 23001 WDFY3 1.74 0.000 55014 STX17 1.74 0.006 10133 OPTN 1.74 0.027 84560 MT4 1.73 0.003 10475 TRIM38 1.73 0.000 200316 APOBEC3F 1.73 0.022 79651 RHBDF2 1.73 0.000 4615 MYD88 1.72 0.000 55577 NAGK 1.72 0.000 2635 GBP3 1.72 0.000 79370 BCL2L14 1.72 0.033 10392 NOD1 1.72 0.045 7726 TRIM26 1.71 0.003 9961 MVP 1.71 0.005 84333 PCGF5 1.71 0.000 140691 TRIM69 1.71 0.013 57669 EPB41L5 1.71 0.020 144423 GLT1D1 1.70 0.035 AFFX- #N/A 1.70 0.013 HUMISGF3A/M97935_3 2533 FYB 1.70 0.000 54149 C21orf91 1.69 0.003

54936 ADPRHL2 1.69 0.011 9473 C1orf38 1.69 0.034 389289 C5orf39 1.69 0.005 3957 LGALS2 1.69 0.030 57130 ATP13A1 1.69 0.010 3290 HSD11B1 1.69 0.035 950 SCARB2 1.69 0.004 201625 DNAH12 1.68 0.005 285761 DCBLD1 1.68 0.034 10537 UBD 1.68 0.024 644 BLVRA 1.68 0.003 728769 LOC728769 1.68 0.000 2180 ACSL1 1.68 0.003 255231 MCOLN2 1.67 0.013 10396 ATP8A1 1.67 0.010 834 CASP1 1.66 0.005 11054 OGFR 1.66 0.027 51299 NRN1 1.65 0.041 132864 CPEB2 1.65 0.015 5366 PMAIP1 1.65 0.006 375790 AGRN 1.65 0.000 9749 PHACTR2 1.65 0.007 84955 NUDCD1 1.64 0.034 8496 PPFIBP1 1.64 0.046 141 ADPRH 1.64 0.003 85363 TRIM5 1.64 0.000 942 CD86 1.63 0.000 1318 SLC31A2 1.63 0.033 60489 APOBEC3G 1.63 0.003 10791 VAMP5 1.63 0.000 253782 LASS6 1.63 0.011 1234 CCR5 1.62 0.038 79993 ELOVL7 1.62 0.019 27348 TOR1B 1.62 0.003 3045 HBD 1.62 0.045 11025 LILRB3 1.62 0.027 56829 ZC3HAV1 1.61 0.000 51131 PHF11 1.61 0.000 80021 TMEM62 1.61 0.000 54507 ADAMTSL4 1.60 0.031 83857 TMTC1 1.59 0.045 5129 PCTK3 1.59 0.011 4210 MEFV 1.59 0.021 201456 FBXO15 1.59 0.007 160428 ALDH1L2 1.59 0.049 79668 PARP8 1.59 0.020 840 CASP7 1.58 0.012 2650 GCNT1 1.58 0.022 6091 ROBO1 1.57 0.003 165631 PARP15 1.57 0.022 80216 ALPK1 1.57 0.005 84441 MAML2 1.57 0.000

9711 KIAA0226 1.57 0.000 11011 TLK2 1.56 0.014 9111 NMI 1.56 0.000 85465 SELI 1.56 0.034 92370 ACPL2 1.56 0.021 64343 AZI2 1.55 0.013 8082 SSPN 1.55 0.015 4067 LYN 1.55 0.003 51237 MGC29506 1.55 0.044 51427 ZNF107 1.55 0.012 79792 GSDMD 1.55 0.009 8869 ST3GAL5 1.54 0.035 2235 FECH 1.53 0.003 2634 GBP2 1.53 0.019 3304 HSPA1B 1.53 0.003 23503 ZFYVE26 1.53 0.000 4704 NDUFA9 1.53 0.035 113829 SLC35A4 1.53 0.010 64167 ERAP2 1.53 0.000 59342 SCPEP1 1.53 0.034 3140 MR1 1.53 0.020 284004 HEXDC 1.53 0.004 27071 DAPP1 1.53 0.034 558 AXL 1.53 0.003 54464 XRN1 1.53 0.003 4683 NBN 1.53 0.000 10346 TRIM22 1.53 0.011 8528 DDO 1.53 0.046 51303 FKBP11 1.52 0.011 84236 RHBDD1 1.52 0.046 4205 MEF2A 1.52 0.011 9963 SLC23A1 1.52 0.024 80231 CXorf21 1.52 0.000 54676 GTPBP2 1.51 0.000 80017 C14orf159 1.51 0.013 6641 SNTB1 1.51 0.044 6453 ITSN1 1.51 0.032 64091 POPDC2 1.50 0.000 8737 RIPK1 1.50 0.020 353376 TICAM2 1.50 0.005 23414 ZFPM2 1.50 0.027 26784 SNORA64 1.50 0.015 51493 C22orf28 1.49 0.005 1506 CTRL 1.49 0.042 646871 RP11-251J8.3 1.49 0.019 283991 FAM100B 1.49 0.003 88523 LOC88523 1.49 0.018 5699 PSMB10 1.48 0.000 7402 UTRN 1.48 0.024 54536 EXOC6 1.48 0.013 441168 FAM26F 1.48 0.034 23216 TBC1D1 1.48 0.038

55669 MFN1 1.48 0.010 896 CCND3 1.48 0.000 23165 NUP205 1.48 0.004 117854 TRIM6 1.47 0.011 80833 APOL3 1.47 0.049 143888 KDELC2 1.47 0.042 63916 ELMO2 1.47 0.035 23604 DAPK2 1.47 0.046 54897 CASZ1 1.46 0.034 253260 RICTOR 1.46 0.005 3779 KCNMB1 1.46 0.003 22849 CPEB3 1.45 0.030 5393 EXOSC9 1.45 0.005 6483 ST3GAL2 1.45 0.011 4192 MDK 1.45 0.024 11080 DNAJB4 1.45 0.003 54823 C1orf26 1.45 0.000 3660 IRF2 1.44 0.033 962 CD48 1.44 0.003 54453 RIN2 1.44 0.007 1540 CYLD 1.44 0.013 55603 FAM46A 1.44 0.003 9725 TMEM63A 1.44 0.000 11133 KPTN 1.43 0.020 1240 CMKLR1 1.43 0.019 7072 TIA1 1.43 0.014 23649 POLA2 1.43 0.046 64976 MRPL40 1.43 0.010 7318 UBA7 1.42 0.029 11044 POLS 1.42 0.005 55072 RNF31 1.42 0.003 7405 UVRAG 1.42 0.000 51510 CHMP5 1.42 0.044 23095 KIF1B 1.42 0.003 9411 ARHGAP29 1.42 0.045 6343 SCT 1.42 0.042 151195 CCNYL1 1.41 0.003 201176 ARHGAP27 1.41 0.005 3569 IL6 1.41 0.046 10518 CIB2 1.41 0.019 51100 SH3GLB1 1.41 0.027 1140 CHRNB1 1.41 0.045 80821 DDHD1 1.40 0.045 24145 PANX1 1.40 0.020 375346 TMEM110 1.40 0.010 5747 PTK2 1.40 0.029 714 C1QC 1.39 0.033 7403 KDM6A 1.39 0.020 55748 CNDP2 1.38 0.030 2213 FCGR2B 1.38 0.019 2710 GK 1.38 0.024 9896 FIG4 1.38 0.034

2820 GPD2 1.38 0.022 222161 DKFZP586I1420 1.38 0.020 3133 HLA-E 1.38 0.019 79627 OGFRL1 1.37 0.041 9759 HDAC4 1.37 0.035 93349 SP140L 1.37 0.021 8837 CFLAR 1.37 0.020 961 CD47 1.37 0.013 3214 HOXB4 1.36 0.045 8792 TNFRSF11A 1.36 0.000 23214 XPO6 1.36 0.005 5686 PSMA5 1.36 0.006 54530 C1orf218 1.36 0.030 84248 FYTTD1 1.36 0.012 10384 BTN3A3 1.36 0.020 26099 C1orf144 1.36 0.041 473 RERE 1.36 0.014 286122 C8orf31 1.36 0.005 2595 GANC 1.36 0.038 5683 PSMA2 1.36 0.000 124446 TMEM219 1.36 0.012 6741 SSB 1.35 0.011 10403 NDC80 1.35 0.003 56894 AGPAT3 1.35 0.021 11105 PRDM7 1.35 0.033 26750 RPS6KC1 1.35 0.000 3162 HMOX1 1.35 0.011 55689 YEATS2 1.35 0.038 55803 ADAP2 1.34 0.042 55234 SMU1 1.34 0.039 3301 DNAJA1 1.34 0.013 79577 CDC73 1.34 0.013 8717 TRADD 1.34 0.003 5533 PPP3CC 1.34 0.005 1519 CTSO 1.34 0.011 6715 SRD5A1 1.34 0.039 51246 SHISA5 1.33 0.000 23549 DNPEP 1.33 0.019 6303 SAT1 1.33 0.020 971 CD72 1.32 0.014 94120 SYTL3 1.32 0.014 645745 MT1P2 1.32 0.021 55183 RIF1 1.32 0.010 9587 MAD2L1BP 1.31 0.020 121260 SLC15A4 1.31 0.024 5732 PTGER2 1.31 0.014 406 ARNTL 1.31 0.033 8850 KAT2B 1.30 0.042 285237 C3orf38 1.30 0.006 2787 GNG5 1.30 0.013 8504 PEX3 1.30 0.031 7097 TLR2 1.30 0.042

221472 FGD2 1.30 0.010 831 CAST 1.29 0.000 7456 WIPF1 1.29 0.033 22797 TFEC 1.29 0.003 64121 RRAGC 1.29 0.010 103 ADAR 1.29 0.000 58533 SNX6 1.28 0.045 1657 DMXL1 1.28 0.020 8573 CASK 1.28 0.005 256586 LYSMD2 1.28 0.020 23597 ACOT9 1.28 0.021 5794 PTPRH 1.28 0.013 5580 PRKCD 1.28 0.021 1649 DDIT3 1.28 0.033 57609 DIP2B 1.27 0.044 23167 EFR3A 1.27 0.000 5875 RABGGTA 1.27 0.012 80025 PANK2 1.27 0.000 55331 ACER3 1.27 0.021 138065 RNF183 1.27 0.035 10307 APBB3 1.26 0.003 6892 TAPBP 1.26 0.039 23077 MYCBP2 1.26 0.022 11177 BAZ1A 1.25 0.038 55770 EXOC2 1.25 0.046 22879 MON1B 1.25 0.045 195827 C9orf21 1.25 0.035 51667 NUB1 1.25 0.003 2332 FMR1 1.25 0.013 5930 RBBP6 1.25 0.016 165324 UBXN2A 1.25 0.022 5685 PSMA4 1.24 0.020 2040 STOM 1.24 0.008 4170 MCL1 1.23 0.014 9465 AKAP7 1.23 0.015 113277 TMEM106A 1.23 0.007 9541 CIR1 1.23 0.000 10179 RBM7 1.23 0.049 57613 KIAA1467 1.22 0.021 3134 HLA-F 1.22 0.012 54187 NANS 1.22 0.024 9592 IER2 1.22 0.039 23071 ERP44 1.22 0.030 27163 NAAA 1.22 0.044 441459 ANKRD18B 1.22 0.046 30 ACAA1 1.21 0.003 6402 SELL 1.21 0.042 5527 PPP2R5C 1.21 0.010 401494 PTPLAD2 1.21 0.011 1032 CDKN2D 1.20 0.033 25977 NECAP1 1.20 0.019 53917 RAB24 1.20 0.030

3998 LMAN1 1.20 0.014 5720 PSME1 1.19 0.042 23200 ATP11B 1.19 0.013 10229 COQ7 1.19 0.033 9938 ARHGAP25 1.19 0.015 3837 KPNB1 1.19 0.038 1472 CST4 1.18 0.038 23607 CD2AP 1.18 0.046 11119 BTN3A1 1.18 0.042 29097 CNIH4 1.17 0.042 25793 FBXO7 1.16 0.039 837 CASP4 1.16 0.010 1889 ECE1 1.16 0.045 9488 PIGB 1.15 0.042 162515 SLC16A11 1.15 0.030 23258 DENND5A 1.14 0.027 2128 EVX1 1.14 0.039 3099 HK2 1.13 0.038 56945 MRPS22 1.13 0.038 5687 PSMA6 1.13 0.045 554175 DNM1P33 1.12 0.045 23588 KLHDC2 0.88 0.045 157869 C8orf84 0.88 0.049 10949 HNRNPA0 0.87 0.049 8842 PROM1 0.87 0.049 23531 MMD 0.86 0.049 3068 HDGF 0.86 0.049 9675 KIAA0406 0.85 0.049 7389 UROD 0.85 0.045 51611 DPH5 0.85 0.046 79622 SNRNP25 0.84 0.045 152217 LOC152217 0.84 0.049 241 ALOX5AP 0.83 0.049 55256 ADI1 0.83 0.045 7075 TIE1 0.83 0.045 10295 BCKDK 0.83 0.049 11339 OIP5 0.82 0.012 10801 SEPT9 0.82 0.045 4311 MME 0.82 0.049 65999 LRRC61 0.82 0.049 11282 MGAT4B 0.81 0.039 79626 TNFAIP8L2 0.81 0.049 65990 FAM173A 0.80 0.049 84861 KLHL22 0.80 0.049 64285 RHBDF1 0.80 0.012 401548 SNX30 0.80 0.049 613 BCR 0.79 0.046 57215 THAP11 0.79 0.045 126259 TMIGD2 0.79 0.045 6477 SIAH1 0.79 0.045 10560 SLC19A2 0.78 0.045 403 ARL3 0.78 0.039

129138 ANKRD54 0.78 0.021 2030 SLC29A1 0.78 0.035 409 ARRB2 0.78 0.033 257236 CCDC96 0.78 0.022 54834 GDAP2 0.77 0.049 79968 WDR76 0.77 0.049 5778 PTPN7 0.77 0.049 11010 GLIPR1 0.76 0.021 8645 KCNK5 0.76 0.012 79956 ERMP1 0.76 0.045 5583 PRKCH 0.76 0.046 22838 RNF44 0.76 0.049 9333 TGM5 0.75 0.049 11163 NUDT4 0.75 0.045 58475 MS4A7 0.75 0.020 10129 FRY 0.75 0.049 51706 CYB5R1 0.74 0.046 10422 UBAC1 0.74 0.045 728926 LOC728926 0.74 0.039 3925 STMN1 0.74 0.015 27433 TOR2A 0.74 0.049 6461 SHB 0.74 0.049 285362 SUMF1 0.73 0.049 5264 PHYH 0.73 0.045 90693 CCDC126 0.73 0.045 5569 PKIA 0.73 0.045 83591 THAP2 0.73 0.011 55357 TBC1D2 0.73 0.049 84947 SERAC1 0.73 0.045 92521 CYTSB 0.73 0.039 1063 CENPF 0.73 0.011 7106 TSPAN4 0.73 0.049 148327 CREB3L4 0.73 0.049 6039 RNASE6 0.72 0.033 283571 PROX2 0.72 0.045 64411 ARAP3 0.71 0.049 27040 LAT 0.71 0.039 27347 STK39 0.71 0.045 10638 SPHAR 0.71 0.045 51533 PHF7 0.71 0.045 23158 TBC1D9 0.70 0.045 54997 TESC 0.70 0.045 127281 C1orf93 0.70 0.045 78996 C7orf49 0.70 0.010 124402 FAM100A 0.70 0.045 9832 JAKMIP2 0.70 0.022 10966 RAB40B 0.70 0.045 255027 MPV17L 0.70 0.011 80823 BHLHB9 0.70 0.045 29904 EEF2K 0.70 0.049 9071 CLDN10 0.69 0.030 5863 RGL2 0.69 0.029

643749 LOC643749 0.69 0.022 24149 ZNF318 0.69 0.012 51744 CD244 0.68 0.045 23625 FAM89B 0.68 0.045 10809 STARD10 0.68 0.046 79901 CYBRD1 0.68 0.049 94031 HTRA3 0.67 0.000 93589 CACNA2D4 0.67 0.045 116159 CYYR1 0.67 0.049 92840 REEP6 0.67 0.010 60468 BACH2 0.67 0.045 118812 MORN4 0.66 0.049 56034 PDGFC 0.66 0.020 284759 SIRPB2 0.65 0.021 79080 CCDC86 0.65 0.049 55534 MAML3 0.65 0.045 6954 TCP11 0.65 0.021 27036 SIGLEC7 0.65 0.010 166012 CHST13 0.64 0.011 4628 MYH10 0.64 0.049 5287 PIK3C2B 0.63 0.049 23129 PLXND1 0.63 0.011 64943 NT5DC2 0.63 0.045 408 ARRB1 0.61 0.021 81848 SPRY4 0.61 0.027 1602 DACH1 0.60 0.049 4815 NINJ2 0.59 0.021 9051 PSTPIP1 0.59 0.049 57523 KIAA1305 0.59 0.011 11098 PRSS23 0.58 0.049 80210 ARMC9 0.58 0.011 728997 LOC728997 0.58 0.021 84660 CCDC62 0.57 0.049 79623 GALNT14 0.57 0.010 30850 CDR2L 0.57 0.022 5738 PTGFRN 0.55 0.049 340895 C10orf112 0.54 0.039 2268 FGR 0.54 0.022 9901 SRGAP3 0.54 0.045 57460 PPM1H 0.54 0.021 10512 SEMA3C 0.52 0.045 64798 DEPDC6 0.51 0.011 83648 FAM167A 0.48 0.045 151473 SLC16A14 0.43 0.045 9705 ST18 0.42 0.049 60437 CDH26 0.42 0.011 284756 C20orf197 0.32 0.045 4283 CXCL9 35.51 0.000 6373 CXCL11 23.28 0.000 6614 SIGLEC1 22.59 0.000 6357 CCL13 20.79 0.042 3429 IFI27 19.85 0.000

8638 OASL 16.17 0.000 200315 APOBEC3A 15.13 0.003 3437 IFIT3 14.27 0.000 5157 PDGFRL 12.03 0.003 116071 BATF2 11.50 0.000 3434 IFIT1 9.84 0.000 2537 IFI6 9.81 0.000 145864 HAPLN3 9.60 0.000 9636 ISG15 9.06 0.000 AFFX- #N/A 8.58 0.000 HUMISGF3A/M97935_MA 2633 GBP1 8.44 0.000 6355 CCL8 8.40 0.021 4938 OAS1 8.09 0.000 3627 CXCL10 7.97 0.010 81030 ZBP1 7.92 0.000 8519 IFITM1 7.89 0.000