Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome

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1 Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome Raphaële Castagné 1,2,3, Michelle Kelly-Irving 2,3, Gianluca Campanella 1, Florence Guida 1, Vittorio Krogh 4, Domenico Palli 5, Salvatore Panico 6, Carlotta Sacerdote 7, Rosario Tumino 8, Jos Kleinjans 9, Theo de Kok 9, Soterios Kyrtopoulos 10, Thierry Lang 2,3, Silvia Stringhini 11, Roel Vermeulen 1,12, Paolo Vineis 1,13,14, Cyrille Delpierre 2,3, a, and Marc Chadeau-Hyam1,14, a, * 1 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, W2 1PG London, UK 2 INSERM, UMR1027, Toulouse F-31000, France 3 Université Toulouse III Paul-Sabatier, UMR1027, Toulouse F-31000, France 4 Epidemiology and Prevention Unit, Fondazione IRCCS- Istituto Nazionale dei Tumori, Via Venezian 1, Milan, Italy 5 Molecular and Nutritional Epidemiology Unit, Istituto per lo Studio e la Prevenzione Oncologica (ISPO Toscana), Via delle Oblate 2, 50141, Florence, Italy 6 Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Naples, Italy 7 Piedmont Reference Centre for Epidemiology and Cancer Prevention (CPO Piemonte), Viale Settimio Severo nr. 65, Turin, Italy 8 Cancer registry and Histopathology Unit, Azienda Ospedaliera Civile M.P.Arezzo, Via Dante N 109, Ragusa, Italy 9 Department of Toxicogenomics, Maastricht University, 6211 LK Maastricht, The Netherlands 10 National Hellenic Research Foundation, Institute of Biology, Pharmaceutical Chemistry and Biotechnology, Vas. Constantinou 48, Athens, Greece 11 Institute of Social and Preventive Medicine, Lausanne University Hospital, Route de la Corniche 10, 1010 Lausanne, Switzerland 12 Institute for Risk Assessment Sciences (IRAS), Utrecht University, PO Box 80178, 3508 TD, Utrecht, The Netherlands. 13 HuGeF, Human Genetics Foundation, Via Nizza 52, Torino, Italy 14 MRC-PHE Centre for Environment and Health, Imperial College, Praed Street Wing, St Mary s Campus, W2 1PG London, UK a C.D. and M.C-H. contributed equally to this work. * To whom correspondence should be addressed. m.chadeau@imperial.ac.uk Supplementary Information

2 Fig. S 1. Inflammatory transcriptome profiling of father s occupational position (N=226). The -log10 p-value is signed by the direction of the effect size estimate and is plotted against each of the 845 genes by sub-pathway. The grey line indicates the per-test significance level controlling the FWER at a 5% level. Results are given for model 1 (see Methods). 2/20

3 Fig. S 2. Inflammatory transcriptome profiling of educational level (N=245). The -log10 p-value is signed by the direction of the effect size estimate and is plotted against each of the 845 genes by sub-pathway. The grey line indicates the per-test significance level controlling the FWER at a 5% level. Results are given for model 1 (see Methods). 3/20

4 Fig. S 3. Inflammatory transcriptome profiling of highest household occupational position (N=229). The -log10 p-value is signed by the direction of the effect size estimate and is plotted against each of the 845 genes by sub-pathway. The grey line indicates the per-test significance level controlling the FWER at a 5% level. Results are given for model 1 (see Methods). 4/20

5 Fig. S 4. Bar plot of the number of unique genes on the x-axis by sub-pathways in inflammation on the y-axis. Percentage of genes within each sub-pathways is also reported in bold. 5/20

6 Fig. S 5. Gene expression level correlation matrix of EPIC-Italy participants in EnviroGenoMarkers (N=246) with pairwise Spearman s rank correlation. 6/20

7 % of variance explained nth component Fig. S 6. Scree plot from the PCA of the 845 gene expression levels. Table S 1. Results for the inflammatory transcriptome profiling (N=845) and each of the three SEP factors. Fold-change (f) is derived from the regression coefficient estimate (β) by the mixed model: f = 2 β. Primary Subpathway Symbol AgilentID EntrezID Father s occ. pos. (N=226) Edu. (N=245) level High. hous. occ. (N=229) f P-value f P-value f P-value Cytokine signaling STAT5B A_23_P E E E-01 Cytokine signaling STAT3 A_24_P E E E-01 Cytokine signaling IL12RB1 A_23_P E E E-01 Cytokine signaling IL18 A_23_P E E E-01 Cytokine signaling IL5RA A_23_P E E E-01 Cytokine signaling CSF1R A_23_P E E E-02 Cytokine signaling EBI3 A_24_P E E E-01 Cytokine signaling CSF2RB A_23_P E E E-01 Cytokine signaling JAK2 A_23_P E E E-01 Cytokine signaling TGFBR1 A_23_P E E E-01 Cytokine signaling IRF2 A_23_P E E E-01 Cytokine signaling CSF3R A_23_P E E E-01 Cytokine signaling IL10 A_23_P E E E-01 Cytokine signaling IL2RA A_23_P E E E-01 Cytokine signaling SOCS2 A_24_P E E E-01 Cytokine signaling IL4R A_23_P E E E-01 Cytokine signaling PIAS2 A_24_P E E E-01 Cytokine signaling IL13RA1 A_24_P E E E-01 Cytokine signaling IL15RA A_23_P E E E-01 Cytokine signaling TBX21 A_23_P E E E-02 Cytokine signaling TYK2 A_23_P E E E-01 Cytokine signaling BMPR1A A_23_P E E E-01 Cytokine signaling ADAM17 A_23_P E E E-01 Cytokine signaling CEBPB A_23_P E E E-01 Cytokine signaling CISH A_23_P E E E-02 Cytokine signaling IL2RG A_23_P E E E-02 Cytokine signaling PIAS3 A_24_P E E E-01 Cytokine signaling IFNG A_23_P E E E-01 Cytokine signaling IL32 A_23_P E E E-01 Cytokine signaling SOCS4 A_23_P E E E-01 Cytokine signaling NMI A_23_P E E E-01 Cytokine signaling IRF4 A_23_P E E E-01 7/20

8 Cytokine signaling PIAS1 A_23_P E E E-01 Cytokine signaling OSM A_23_P E E E-01 Cytokine signaling IL17B A_23_P E E E-01 Cytokine signaling IL17F A_23_P E E E-01 Cytokine signaling IL1RAP A_23_P E E E-01 Cytokine signaling IFNAR1 A_23_P E E E-01 Cytokine signaling IL17RA A_32_P E E E-01 Cytokine signaling CASP1 A_23_P E E E-01 Cytokine signaling IL10RA A_23_P E E E-01 Cytokine signaling SOCS3 A_23_P E E E-01 Cytokine signaling STAT5A A_24_P E E E-01 Cytokine signaling PTPN2 A_23_P E E E-01 Cytokine signaling IL1RN A_23_P E E E-01 Cytokine signaling IFNAR2 A_23_P E E E-01 Cytokine signaling TGFBR2 A_23_P E E E-01 Cytokine signaling IL4 A_23_P E E E-01 Cytokine signaling S100A9 A_23_P E E E-01 Cytokine signaling IL3RA A_32_P E E E-01 Cytokine signaling ILF2 A_23_P E E E-01 Cytokine signaling IL27RA A_24_P E E E-02 Cytokine signaling IRF3 A_23_P E E E-01 Cytokine signaling IL18RAP A_23_P E E E-01 Cytokine signaling IFNGR2 A_23_P E E E-01 Cytokine signaling IL15 A_23_P E E E-01 Cytokine signaling STAT4 A_23_P E E E-01 Cytokine signaling NFIL3 A_23_P E E E-01 Cytokine signaling JAK3 A_24_P E E E-01 Cytokine signaling IRF8 A_23_P E E E-01 Cytokine signaling IL17A A_23_P E E E-01 Cytokine signaling IL7R A_23_P E E E-01 Cytokine signaling IL29 A_23_P E E E-01 Cytokine signaling PTPN1 A_23_P E E E-02 Cytokine signaling IL1F6 A_23_P E E E-01 Cytokine signaling IL19 A_23_P E E E-01 Cytokine signaling ACE A_24_P E E E-01 Cytokine signaling CSF1 A_23_P E E E-01 Cytokine signaling IL28A A_23_P E E E-01 Cytokine signaling IRF1 A_23_P E E E-01 Cytokine signaling SOCS1 A_23_P E E E-01 Cytokine signaling PDGFRB A_23_P E E E-01 Cytokine signaling IL31RA A_23_P E E E-01 Cytokine signaling IL23R A_23_P E E E-01 Cytokine signaling S100A8 A_23_P E E E-01 Cytokine signaling STAT6 A_23_P E E E-01 Cytokine signaling IRF5 A_24_P E E E-01 Cytokine signaling IL1F10 A_23_P E E E-02 Cytokine signaling IL6ST A_24_P E E E-01 Cytokine signaling TXLNA A_23_P E E E-01 Cytokine signaling IL24 A_23_P E E E-01 Cytokine signaling IL1F7 A_23_P E E E-01 Cytokine signaling IL1RL2 A_23_P E E E-01 Cytokine signaling STAT1 A_23_P E E E-01 Cytokine signaling SOCS5 A_23_P E E E-01 Cytokine signaling IL16 A_24_P E E E-01 Cytokine signaling IL1R1 A_24_P E E E-01 Cytokine signaling IL6 A_23_P E E E-01 Cytokine signaling IFNB1 A_23_P E E E-01 Cytokine signaling IL12RB2 A_23_P E E E-04 Cytokine signaling S100A12 A_23_P E E E-02 Cytokine signaling GATA3 A_23_P E E E-01 Cytokine signaling STAT2 A_23_P E E E-01 Cytokine signaling IL1R2 A_24_P E E E-01 Cytokine signaling IL1B A_23_P E E E-01 Cytokine signaling TGIF2 A_23_P E E E-01 Cytokine signaling IFNGR1 A_23_P E E E-01 Cytokine signaling ENG A_23_P E E E-01 Cytokine signaling TGFB3 A_23_P E E E-01 Cytokine signaling IL7 A_23_P E E E-01 Cytokine signaling PIAS4 A_23_P E E E-01 Cytokine signaling AGER A_23_P E E E-01 Cytokine signaling BMPR2 A_24_P E E E-01 Cytokine signaling JAK1 A_24_P E E E-01 Cytokine signaling HMGB1 A_24_P E E E-01 Cytokine signaling IRF7 A_24_P E E E-01 Cytokine signaling LIF A_24_P E E E-01 Cytokine signaling IL2RB A_24_P E E E-01 Cytokine signaling IL18R1 A_24_P E E E-01 Cytokine signaling IL21R A_24_P E E E-01 Cytokine signaling IL10RB A_24_P E E E-01 Cytokine signaling PDGFB A_24_P E E E-01 Cytokine signaling CRP A_24_P E E E-01 Cytokine signaling THPO A_24_P E E E-01 Cytokine signaling IL6R A_24_P E E E-01 8/20

9 Cytokine signaling IFNA4 A_24_P E E E-01 Cytokine signaling TGFB1 A_24_P E E E-02 Cytokine signaling SOCS6 A_24_P E E E-01 Cytokine signaling IL8 A_32_P E E E-01 MAPK signaling YWHAH A_23_P E E E-01 MAPK signaling PPP2R3A A_24_P E E E-01 MAPK signaling ATF1 A_23_P E E E-01 MAPK signaling FOS A_23_P E E E-01 MAPK signaling PPP2R1A A_23_P E E E-01 MAPK signaling DUSP2 A_24_P E E E-01 MAPK signaling DUSP1 A_23_P E E E-01 MAPK signaling RASGRP1 A_32_P E E E-01 MAPK signaling HDAC1 A_23_P E E E-01 MAPK signaling PLA2G4A A_23_P E E E-01 MAPK signaling SOS2 A_23_P E E E-01 MAPK signaling MAP2K3 A_24_P E E E-01 MAPK signaling YWHAB A_23_P E E E-02 MAPK signaling ATF4 A_23_P E E E-01 MAPK signaling PPP2CA A_23_P E E E-01 MAPK signaling HDAC2 A_23_P E E E-01 MAPK signaling YWHAG A_24_P E E E-01 MAPK signaling ETS1 A_23_P E E E-01 MAPK signaling YWHAQ A_24_P E E E-01 MAPK signaling MAP3K5 A_23_P E E E-02 MAPK signaling PPP2CB A_23_P E E E-01 MAPK signaling DUSP4 A_23_P E E E-01 MAPK signaling PRKCQ A_23_P E E E-01 MAPK signaling DUSP6 A_23_P E E E-01 MAPK signaling PRKCD A_23_P E E E-01 MAPK signaling MAPK13 A_24_P E E E-01 MAPK signaling LYN A_23_P E E E-01 MAPK signaling MAX A_23_P E E E-01 MAPK signaling PPM1A A_23_P E E E-01 MAPK signaling PPP1R7 A_23_P E E E-01 MAPK signaling EGF A_23_P E E E-01 MAPK signaling IFI16 A_23_P E E E-01 MAPK signaling FOSL1 A_23_P E E E-01 MAPK signaling MAPK9 A_23_P E E E-01 MAPK signaling KCNH8 A_23_P E E E-01 MAPK signaling ELK1 A_23_P E E E-01 MAPK signaling RASA1 A_23_P E E E-01 MAPK signaling INS A_23_P E E E-01 MAPK signaling MKNK1 A_23_P E E E-01 MAPK signaling SHC1 A_24_P E E E-01 MAPK signaling MAPKAPK2 A_23_P E E E-01 MAPK signaling JUN A_23_P E E E-01 MAPK signaling MAP2K1 A_23_P E E E-02 MAPK signaling MAPK8 A_23_P E E E-01 MAPK signaling MADD A_23_P E E E-01 MAPK signaling PPP1CC A_23_P E E E-01 MAPK signaling MAP2K6 A_23_P E E E-01 MAPK signaling KSR1 A_24_P E E E-01 MAPK signaling MAP2K2 A_23_P E E E-01 MAPK signaling ATF2 A_23_P E E E-01 MAPK signaling DDIT3 A_23_P E E E-01 MAPK signaling PPP2R2B A_23_P E E E-01 MAPK signaling RAC1 A_32_P E E E-02 MAPK signaling MYC A_24_P E E E-01 MAPK signaling RAC2 A_24_P E E E-01 MAPK signaling PTK2 A_23_P E E E-01 MAPK signaling PRKCE A_23_P E E E-01 MAPK signaling PLCG1 A_23_P E E E-01 MAPK signaling HSPB1 A_24_P E E E-01 MAPK signaling MAPK1 A_23_P E E E-01 MAPK signaling ETS2 A_24_P E E E-01 MAPK signaling PPP1CB A_24_P E E E-01 MAPK signaling MAPK12 A_23_P E E E-01 MAPK signaling MYCN A_24_P E E E-01 MAPK signaling RAPGEF1 A_23_P E E E-01 MAPK signaling KRAS A_23_P E E E-01 MAPK signaling SRC A_23_P E E E-01 MAPK signaling MAPKAPK3 A_23_P E E E-01 MAPK signaling MEF2C A_23_P E E E-01 MAPK signaling PPP1CA A_23_P E E E-02 MAPK signaling MEF2D A_23_P E E E-01 MAPK signaling SOS1 A_23_P E E E-01 MAPK signaling ATF3 A_23_P E E E-01 MAPK signaling MEF2A A_24_P E E E-01 MAPK signaling RPS6KA4 A_23_P E E E-02 MAPK signaling JUND A_23_P E E E-01 MAPK signaling RPS6KA5 A_24_P E E E-01 MAPK signaling MAPK3 A_23_P E E E-01 MAPK signaling EP300 A_23_P E E E-01 9/20

10 MAPK signaling RAF1 A_23_P E E E-01 MAPK signaling MAP3K1 A_23_P E E E-01 MAPK signaling MAPK14 A_24_P E E E-02 MAPK signaling BRAF A_23_P E E E-01 MAPK signaling RAP1GAP A_24_P E E E-01 MAPK signaling MAP4K1 A_23_P E E E-01 MAPK signaling MAP3K7 A_23_P E E E-01 MAPK signaling MAPK11 A_23_P E E E-01 MAPK signaling PRKCZ A_24_P E E E-01 MAPK signaling RAP1A A_23_P E E E-01 MAPK signaling DUSP10 A_23_P E E E-01 MAPK signaling PPP2R1B A_23_P E E E-01 MAPK signaling PRKCA A_24_P E E E-01 MAPK signaling NRAS A_23_P E E E-01 MAPK signaling BCAR1 A_23_P E E E-01 MAPK signaling ARAF A_23_P E E E-01 MAPK signaling PAK1 A_23_P E E E-01 MAPK signaling TLN1 A_24_P E E E-01 MAPK signaling HRAS A_23_P E E E-01 MAPK signaling MAPKAPK5 A_24_P E E E-01 MAPK signaling EEF2K A_24_P E E E-01 MAPK signaling MAP3K6 A_24_P E E E-01 MAPK signaling YWHAZ A_32_P E E E-01 MAPK signaling TLN2 A_24_P E E E-01 MAPK signaling ESR1 A_24_P E E E-01 MAPK signaling RPS6KA1 A_24_P E E E-01 MAPK signaling HMGN1 A_32_P E E E-01 MAPK signaling DUSP9 A_24_P E E E-01 MAPK signaling HINT1 A_32_P E E E-01 MAPK signaling RAPGEF3 A_32_P E E E-01 MAPK signaling MAP2K4 A_32_P E E E-01 MAPK signaling PTPRK A_32_P E E E-01 Adhesion Extravasation Migration SELL A_23_P E E E-01 Adhesion Extravasation Migration ITGB1 A_32_P E E E-01 Adhesion Extravasation Migration CXCR6 A_23_P E E E-01 Adhesion Extravasation Migration CXCL5 A_23_P E E E-01 Adhesion Extravasation Migration NT5E A_24_P E E E-01 Adhesion Extravasation Migration CD36 A_24_P E E E-01 Adhesion Extravasation Migration CCL21 A_23_P E E E-01 Adhesion Extravasation Migration DARC A_23_P E E E-01 Adhesion Extravasation Migration CKLF A_24_P E E E-02 Adhesion Extravasation Migration VASP A_23_P E E E-01 Adhesion Extravasation Migration ICAM5 A_24_P E E E-01 Adhesion Extravasation Migration JAM2 A_23_P E E E-01 Adhesion Extravasation Migration PPBP A_23_P E E E-01 Adhesion Extravasation Migration FYB A_24_P E E E-01 Adhesion Extravasation Migration CCL19 A_23_P E E E-01 Adhesion Extravasation Migration ITGAM A_23_P E E E-01 Adhesion Extravasation Migration SIPA1 A_23_P E E E-01 Adhesion Extravasation Migration FUT4 A_24_P E E E-01 Adhesion Extravasation Migration ITGAD A_23_P E E E-02 Adhesion Extravasation Migration CEACAM3 A_23_P E E E-01 Adhesion Extravasation Migration CCL27 A_23_P E E E-01 Adhesion Extravasation Migration SELP A_23_P E E E-02 Adhesion Extravasation Migration MUC1 A_23_P E E E-01 Adhesion Extravasation Migration CD58 A_23_P E E E-01 Adhesion Extravasation Migration PXN A_23_P E E E-01 Adhesion Extravasation Migration PTPRU A_23_P E E E-01 Adhesion Extravasation Migration ICAM2 A_23_P E E E-02 Adhesion Extravasation Migration CCL5 A_23_P E E E-03 Adhesion Extravasation Migration ICAM1 A_23_P E E E-01 Adhesion Extravasation Migration CD2 A_23_P E E E-01 Adhesion Extravasation Migration MYH10 A_23_P E E E-01 Adhesion Extravasation Migration PLAUR A_23_P E E E-01 Adhesion Extravasation Migration ICAM3 A_23_P E E E-01 Adhesion Extravasation Migration MMP1 A_23_P E E E-01 Adhesion Extravasation Migration SIGLEC1 A_23_P E E E-01 Adhesion Extravasation Migration XCR1 A_23_P E E E-01 Adhesion Extravasation Migration CXCL9 A_23_P E E E-01 Adhesion Extravasation Migration RASSF5 A_24_P E E E-01 Adhesion Extravasation Migration VCL A_24_P E E E-02 Adhesion Extravasation Migration CXCL12 A_23_P E E E-01 Adhesion Extravasation Migration CTTN A_23_P E E E-01 Adhesion Extravasation Migration MMP19 A_23_P E E E-01 Adhesion Extravasation Migration ITGAL A_23_P E E E-02 Adhesion Extravasation Migration CCL4 A_23_P E E E-01 Adhesion Extravasation Migration ALS2 A_23_P E E E-02 Adhesion Extravasation Migration ROCK2 A_24_P E E E-01 Adhesion Extravasation Migration ITGA6 A_23_P E E E-02 Adhesion Extravasation Migration CCR2 A_23_P E E E-02 Adhesion Extravasation Migration CCL24 A_23_P E E E-01 Adhesion Extravasation Migration CD99 A_24_P E E E-03 Adhesion Extravasation Migration JAM3 A_23_P E E E-02 10/20

11 Adhesion Extravasation Migration ITGAE A_23_P E E E-02 Adhesion Extravasation Migration CCR3 A_24_P E E E-01 Adhesion Extravasation Migration CTNND1 A_23_P E E E-01 Adhesion Extravasation Migration PECAM1 A_23_P E E E-01 Adhesion Extravasation Migration ITGA1 A_23_P E E E-01 Adhesion Extravasation Migration CCL17 A_23_P E E E-01 Adhesion Extravasation Migration ITGAX A_23_P E E E-01 Adhesion Extravasation Migration ARHGAP1 A_23_P E E E-01 Adhesion Extravasation Migration CXCL2 A_23_P E E E-01 Adhesion Extravasation Migration ITGB2 A_23_P E E E-01 Adhesion Extravasation Migration CD33 A_24_P E E E-02 Adhesion Extravasation Migration CCR7 A_23_P E E E-01 Adhesion Extravasation Migration MYL6 A_23_P E E E-01 Adhesion Extravasation Migration THY1 A_23_P E E E-01 Adhesion Extravasation Migration ITGA5 A_23_P E E E-01 Adhesion Extravasation Migration CEACAM8 A_23_P E E E-01 Adhesion Extravasation Migration CXCL16 A_23_P E E E-01 Adhesion Extravasation Migration ITGB3 A_24_P E E E-01 Adhesion Extravasation Migration MMP9 A_23_P E E E-01 Adhesion Extravasation Migration CX3CR1 A_23_P E E E-01 Adhesion Extravasation Migration ALCAM A_32_P E E E-01 Adhesion Extravasation Migration CCR5 A_23_P E E E-01 Adhesion Extravasation Migration SPN A_24_P E E E-02 Adhesion Extravasation Migration CEACAM1 A_23_P E E E-01 Adhesion Extravasation Migration CD96 A_23_P E E E-01 Adhesion Extravasation Migration CD97 A_23_P E E E-01 Adhesion Extravasation Migration CCL28 A_23_P E E E-01 Adhesion Extravasation Migration ITGAV A_23_P E E E-01 Adhesion Extravasation Migration ITGA4 A_23_P E E E-01 Adhesion Extravasation Migration MYH9 A_24_P E E E-01 Adhesion Extravasation Migration RHOH A_23_P E E E-01 Adhesion Extravasation Migration SELPLG A_23_P E E E-01 Adhesion Extravasation Migration ITGB4 A_23_P E E E-01 Adhesion Extravasation Migration CCR1 A_24_P E E E-01 Adhesion Extravasation Migration CCRL2 A_24_P E E E-01 Adhesion Extravasation Migration CD47 A_24_P E E E-01 Adhesion Extravasation Migration RHOA A_23_P E E E-01 Adhesion Extravasation Migration HMMR A_23_P E E E-01 Adhesion Extravasation Migration CXCL1 A_23_P E E E-01 Adhesion Extravasation Migration CCR4 A_23_P E E E-01 Adhesion Extravasation Migration CD48 A_23_P E E E-01 Adhesion Extravasation Migration CD9 A_23_P E E E-01 Adhesion Extravasation Migration ITGB7 A_23_P E E E-01 Adhesion Extravasation Migration ITGA2B A_23_P E E E-02 Adhesion Extravasation Migration CD226 A_23_P E E E-01 Adhesion Extravasation Migration CRK A_24_P E E E-01 Adhesion Extravasation Migration CCL2 A_23_P E E E-01 Adhesion Extravasation Migration MIF A_23_P E E E-02 Adhesion Extravasation Migration CCBP2 A_23_P E E E-01 Adhesion Extravasation Migration CXCL3 A_24_P E E E-01 Adhesion Extravasation Migration CCR6 A_24_P E E E-01 Adhesion Extravasation Migration ADAM8 A_24_P E E E-01 Adhesion Extravasation Migration CCL15 A_24_P E E E-01 Adhesion Extravasation Migration CCL23 A_24_P E E E-01 Adhesion Extravasation Migration F11R A_24_P E E E-02 Adhesion Extravasation Migration CX3CL1 A_24_P E E E-01 Adhesion Extravasation Migration XCL1 A_24_P E E E-01 Adhesion Extravasation Migration MMP14 A_24_P E E E-01 Adhesion Extravasation Migration ITGA2 A_32_P E E E-02 Leukocyte signaling MARCO A_23_P E E E-03 Leukocyte signaling CTLA4 A_23_P E E E-01 Leukocyte signaling LCK A_23_P E E E-01 Leukocyte signaling FCER1A A_23_P E E E-01 Leukocyte signaling PIK3AP1 A_23_P E E E-02 Leukocyte signaling CD79A A_23_P E E E-01 Leukocyte signaling LILRA5 A_24_P E E E-02 Leukocyte signaling CD86 A_24_P E E E-01 Leukocyte signaling SH3BP2 A_24_P E E E-01 Leukocyte signaling MS4A1 A_23_P E E E-01 Leukocyte signaling IGLL1 A_24_P E E E-01 Leukocyte signaling PTPRC A_23_P E E E-01 Leukocyte signaling IGHA1 A_23_P E E E-01 Leukocyte signaling SCARF2 A_24_P E E E-03 Leukocyte signaling BTK A_23_P E E E-01 Leukocyte signaling LILRA2 A_23_P E E E-02 Leukocyte signaling SLA2 A_23_P E E E-02 Leukocyte signaling GRAP2 A_24_P E E E-01 Leukocyte signaling PTPN22 A_23_P E E E-01 Leukocyte signaling SCGB1A1 A_23_P E E E-01 Leukocyte signaling CSK A_23_P E E E-01 Leukocyte signaling CD68 A_23_P E E E-02 Leukocyte signaling SCARF1 A_23_P E E E-01 Leukocyte signaling FOXP3 A_23_P E E E-01 11/20

12 Leukocyte signaling SIGLEC5 A_24_P E E E-01 Leukocyte signaling FCER1G A_23_P E E E-01 Leukocyte signaling FCER2 A_23_P E E E-01 Leukocyte signaling ICOSLG A_23_P E E E-01 Leukocyte signaling CD38 A_23_P E E E-01 Leukocyte signaling MAL A_23_P E E E-01 Leukocyte signaling SIRPB1 A_24_P E E E-01 Leukocyte signaling MS4A2 A_23_P E E E-01 Leukocyte signaling TREM1 A_23_P E E E-01 Leukocyte signaling PILRB A_23_P E E E-01 Leukocyte signaling PTPN7 A_23_P E E E-01 Leukocyte signaling CD79B A_23_P E E E-01 Leukocyte signaling SECTM1 A_24_P E E E-02 Leukocyte signaling SIGLEC10 A_23_P E E E-01 Leukocyte signaling LILRB2 A_23_P E E E-01 Leukocyte signaling FCAR A_24_P E E E-01 Leukocyte signaling CD22 A_24_P E E E-01 Leukocyte signaling TEC A_23_P E E E-01 Leukocyte signaling CD44 A_23_P E E E-02 Leukocyte signaling DAPP1 A_23_P E E E-01 Leukocyte signaling MST1R A_23_P E E E-01 Leukocyte signaling SHB A_24_P E E E-01 Leukocyte signaling LILRP2 A_23_P E E E-01 Leukocyte signaling SIRPG A_23_P E E E-01 Leukocyte signaling VPREB1 A_23_P E E E-02 Leukocyte signaling TXK A_24_P E E E-01 Leukocyte signaling SCGB3A1 A_23_P E E E-01 Leukocyte signaling LCP2 A_23_P E E E-01 Leukocyte signaling CBL A_23_P E E E-01 Leukocyte signaling FCGR2B A_23_P E E E-01 Leukocyte signaling PAG1 A_32_P E E E-01 Leukocyte signaling SH2D1B A_23_P E E E-01 Leukocyte signaling ITK A_23_P E E E-01 Leukocyte signaling LRRC23 A_23_P E E E-01 Leukocyte signaling LILRB3 A_32_P E E E-01 Leukocyte signaling TFEB A_23_P E E E-01 Leukocyte signaling ICOS A_23_P E E E-01 Leukocyte signaling SLC7A5 A_23_P E E E-01 Leukocyte signaling VAV1 A_23_P E E E-01 Leukocyte signaling ZAP70 A_23_P E E E-01 Leukocyte signaling PTPRJ A_23_P E E E-01 Leukocyte signaling CD3E A_24_P E E E-01 Leukocyte signaling LAT A_23_P E E E-01 Leukocyte signaling FYN A_23_P E E E-01 Leukocyte signaling PTAFR A_23_P E E E-01 Leukocyte signaling CD40 A_23_P E E E-01 Leukocyte signaling ABL1 A_24_P E E E-01 Leukocyte signaling CD40LG A_23_P E E E-01 Leukocyte signaling SLAMF1 A_23_P E E E-01 Leukocyte signaling CST7 A_23_P E E E-03 Leukocyte signaling CD53 A_23_P E E E-01 Leukocyte signaling TCIRG1 A_23_P E E E-01 Leukocyte signaling SLC3A2 A_23_P E E E-01 Leukocyte signaling TCF7 A_23_P E E E-01 Leukocyte signaling GRB2 A_24_P E E E-02 Leukocyte signaling FLT3LG A_23_P E E E-02 Leukocyte signaling LILRA3 A_23_P E E E-03 Leukocyte signaling FCGR2A A_23_P E E E-01 Leukocyte signaling CD52 A_23_P E E E-01 Leukocyte signaling LILRA4 A_23_P E E E-02 Leukocyte signaling CD28 A_23_P E E E-01 Leukocyte signaling SYK A_23_P E E E-01 Leukocyte signaling SLAMF9 A_23_P E E E-01 Leukocyte signaling FLT3 A_23_P E E E-01 Leukocyte signaling TACR1 A_24_P E E E-01 Leukocyte signaling EDNRA A_24_P E E E-01 Leukocyte signaling SEMA4D A_24_P E E E-01 Leukocyte signaling CD4 A_24_P E E E-01 Leukocyte signaling CD80 A_24_P E E E-01 Leukocyte signaling LILRA1 A_24_P E E E-01 Leukocyte signaling SLAMF7 A_24_P E E E-02 Leukocyte signaling CD5 A_24_P E E E-01 Leukocyte signaling SLAMF6 A_24_P E E E-01 Leukocyte signaling BLNK A_24_P E E E-01 Leukocyte signaling LILRB4 A_24_P E E E-01 Leukocyte signaling CD37 A_24_P E E E-01 Leukocyte signaling PAX5 A_24_P E E E-01 Leukocyte signaling DPP4 A_24_P E E E-01 Leukocyte signaling CD8A A_32_P E E E-01 Apoptosis Signaling BCL2L13 A_24_P E E E-01 Apoptosis Signaling PARP1 A_23_P E E E-01 Apoptosis Signaling TNFSF10 A_23_P E E E-01 Apoptosis Signaling DFFA A_23_P E E E-01 12/20

13 Apoptosis Signaling DAXX A_23_P E E E-01 Apoptosis Signaling CASP7 A_23_P E E E-02 Apoptosis Signaling BCL2L14 A_23_P E E E-01 Apoptosis Signaling ROCK1 A_24_P E E E-01 Apoptosis Signaling CAPN1 A_24_P E E E-01 Apoptosis Signaling ACIN1 A_23_P E E E-01 Apoptosis Signaling BAK1 A_23_P E E E-01 Apoptosis Signaling RIPK3 A_23_P E E E-01 Apoptosis Signaling BAD A_23_P E E E-01 Apoptosis Signaling BCL2A1 A_23_P E E E-01 Apoptosis Signaling TANK A_23_P E E E-01 Apoptosis Signaling BCL2L11 A_24_P E E E-02 Apoptosis Signaling BID A_24_P E E E-01 Apoptosis Signaling TNFRSF10B A_24_P E E E-02 Apoptosis Signaling PTPN13 A_23_P E E E-01 Apoptosis Signaling BCL2 A_23_P E E E-01 Apoptosis Signaling SPTAN1 A_23_P E E E-01 Apoptosis Signaling BAX A_23_P E E E-02 Apoptosis Signaling CASP8 A_24_P E E E-01 Apoptosis Signaling CFLAR A_24_P E E E-01 Apoptosis Signaling CASP10 A_24_P E E E-01 Apoptosis Signaling BCL2L1 A_24_P E E E-01 Apoptosis Signaling CAPN2 A_23_P E E E-01 Apoptosis Signaling RIPK2 A_23_P E E E-01 Apoptosis Signaling DAPK1 A_23_P E E E-02 Apoptosis Signaling FAIM A_23_P E E E-01 Apoptosis Signaling TNFRSF10A A_23_P E E E-01 Apoptosis Signaling TNFRSF10C A_23_P E E E-01 Apoptosis Signaling TP53 A_23_P E E E-01 Apoptosis Signaling TNFRSF21 A_23_P E E E-01 Apoptosis Signaling CAPN10 A_23_P E E E-02 Apoptosis Signaling LMNA A_23_P E E E-02 Apoptosis Signaling APAF1 A_23_P E E E-01 Apoptosis Signaling FASLG A_23_P E E E-01 Apoptosis Signaling BBC3 A_24_P E E E-01 Apoptosis Signaling CASP2 A_24_P E E E-01 Apoptosis Signaling BIK A_23_P E E E-01 Apoptosis Signaling BCL2L2 A_23_P E E E-02 Apoptosis Signaling DFFB A_23_P E E E-01 Apoptosis Signaling DIABLO A_23_P E E E-01 Apoptosis Signaling CASP6 A_23_P E E E-01 Apoptosis Signaling BCL2L12 A_23_P E E E-01 Apoptosis Signaling CASP8AP2 A_23_P E E E-01 Apoptosis Signaling DAP3 A_23_P E E E-01 Apoptosis Signaling FAS A_23_P E E E-01 Apoptosis Signaling CAPNS1 A_23_P E E E-02 Apoptosis Signaling ENDOG A_23_P E E E-01 Apoptosis Signaling FADD A_23_P E E E-01 Apoptosis Signaling CASP14 A_23_P E E E-01 Apoptosis Signaling CASP3 A_23_P E E E-01 Apoptosis Signaling DAP A_23_P E E E-03 Apoptosis Signaling TNFRSF10D A_23_P E E E-01 Apoptosis Signaling CASP9 A_24_P E E E-01 Apoptosis Signaling BIRC3 A_23_P E E E-01 Apoptosis Signaling BIRC2 A_24_P E E E-01 Apoptosis Signaling GAS2 A_24_P E E E-01 Apoptosis Signaling CYCS A_24_P E E E-01 Apoptosis Signaling MCL1 A_24_P E E E-01 Apoptosis Signaling HTRA2 A_24_P E E E-01 Apoptosis Signaling CRADD A_32_P E E E-01 Phagocytosis Ag presentation PSMB9 A_23_P E E E-01 Phagocytosis Ag presentation LAG3 A_23_P E E E-02 Phagocytosis Ag presentation XBP1 A_24_P E E E-02 Phagocytosis Ag presentation HLA-B A_23_P E E E-01 Phagocytosis Ag presentation RFX1 A_23_P E E E-01 Phagocytosis Ag presentation PSMA1 A_23_P E E E-01 Phagocytosis Ag presentation PSME1 A_23_P E E E-01 Phagocytosis Ag presentation IFI30 A_23_P E E E-01 Phagocytosis Ag presentation LILRB5 A_23_P E E E-01 Phagocytosis Ag presentation RFXANK A_23_P E E E-01 Phagocytosis Ag presentation HLA-DQB2 A_23_P E E E-01 Phagocytosis Ag presentation TAP2 A_23_P E E E-01 Phagocytosis Ag presentation HLA-DPB1 A_23_P E E E-01 Phagocytosis Ag presentation TAPBP A_23_P E E E-01 Phagocytosis Ag presentation NFX1 A_23_P E E E-01 Phagocytosis Ag presentation HLA-DPA1 A_23_P E E E-01 Phagocytosis Ag presentation HLA-DOA A_24_P E E E-01 Phagocytosis Ag presentation CIITA A_23_P E E E-01 Phagocytosis Ag presentation PRSS16 A_23_P E E E-01 Phagocytosis Ag presentation CD1B A_23_P E E E-01 Phagocytosis Ag presentation PSMB5 A_23_P E E E-01 Phagocytosis Ag presentation CD1A A_23_P E E E-01 Phagocytosis Ag presentation HLA-A A_24_P E E E-02 13/20

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