Supplementary Table S5: Canonical pathways activated or inhibited in responding vs non-responding patients Ingenuity Time canonical -log (p-value) Z-score Genesa pathways Baseline HLA-DQA2, ICOS, HLA-DQA1, PRKCQ, PIK3R5, HLA-DQB2, IL10RA, IFNGR1, HLA-DRB1, HLA-DMA, CD3D, HLA-DRB5, HLA-DPA1, HLA-DMB, FGFR4, HLA- Th1 Pathway 5.3 3.8 DPB1, IL2, TNFSF11, HLA-DOA, CD3G, HLA-DOB, KLRC1, HLA-DRA, KLRD1, CD40LG, CD247 HLA-DQA2, ICOS, HLA-DQA1, PRKCQ, PIK3R5, IL13, IKZF1, HLA-DQB2, CXCR6, HLA-DRB1, HLA-DMA, CD3D, HLA-DRB5, HLA-DPA1, HLA-DMB, Th2 Pathway 4.9 2.5 CCR4, IL17RB, FGFR4, HLA-DPB1, IL2, HLA-DOA, CD3G, HLA-DOB, HLA-DRA, TGFBR2, CCR3, CD247 CCR7, IL15, HLA-DQA1, PLCB2, PIK3R5, CD1C, FCGR2C, CD83, IRF8, HLA- Dendritic Cell DRB1, HLA-DMA, HLA-DRB5, HLA-DMB, IGHG1, CD1B, FGFR4, IGHG4, TLR2, 4.5 3.4 Maturation NOTUM, FSCN1, HLA-DOA, CD1A, MAPK12, HLA-DOB, LY75, HLA-DRA, FCGR2B, CD40LG, IGHG2, COL2A1, IGHG3 Calcium-induced T HLA-DOA, CD3G, HLA-DQA1, PRKCQ, NR4A1, HLA-DOB, HLA-DRA, HLA- Lymphocyte 3.6 2.7 DRB1, HLA-DMA, CD3D, HLA-DRB5, HLA-DMB, CD247, ZAP70 Apoptosis iCOS-iCOSL IL2, ICOS, HLA-DOA, CD3G, HLA-DQA1, PRKCQ, PIK3R5, HLA-DOB, HLA-DRA, Signalling in T 3.2 2.7 INPP5D, CD40LG, HLA-DRB1, HLA-DMA, CD3D, HLA-DRB5, HLA-DMB, Helper Cells PTPRC, FGFR4, CD247, ZAP70 PLA2G2D, CXCL12, TLR5, GJB1, GAD1, HLA-DQA1, PIK3R5, SLC6A13, BIRC3, IFNGR1, TLR8, SYK, MAPK4, HLA-DRB1, IL1R1, HLA-DMA, HLA-DRB5, HLA- Neuroinflammation 2.3 3.2 DMB, BIRC7, SLC1A3, FGFR4, TLR2, TLR7, CCL5, HLA-DOA, MAPK12, BIRC5, Signalling Pathway HLA-DOB, GABRA2, HLA-DRA, GDNF, TGFBR2, KCNJ5, PLA2G12B, TLR10, CYBB ADRB2, NPY1R, AGTR1, FFAR3, P2RY12, PDE7A, TBXA2R, P2RY13, PRKAR1B, cAMP-mediated 2.3 3.7 CCR4, LHCGR, AKAP11, GPR17, ADCY8, VIPR2, ADCY5, HTR1D, ADCY7, signalling VIPR1, PTGER4, CAMK1D, CNR2, CHRM2, MC1R, HTR6, ADORA3, GRM6, HTR4 Role of NFAT in HLA-DOA, CD3G, HLA-DQA1, PLCB2, PRKCQ, PIK3R5, HLA-DOB, FCER1A, Regulation of the 2.3 3.5 FCGR2C, HLA-DRA, SYK, FCGR2B, HLA-DRB1, HLA-DMA, CD3D, HLA-DRB5, Immune Response GNG4, HLA-DMB, BLNK, FGFR4, CD79A, CD247, HRAS, ZAP70 Week 4 JUN, IL1RL1, HLA-DQA2, PIK3R6, TGFB1, HLA-DQA1, SOCS3, CCR1, JAK3, Th2 Pathway 8.5 2.2 PIK3R5, IL2RB, ITGB2, IL2RG, HLA-DQB2, CXCR6, HLA-DRB1, HLA-DMA, Ingenuity Time canonical -log (p-value) Z-score Genesa pathways HLA-DRB5, IL24, BHLHE41, HLA-DMB, HLA-DPA1, CD4, FGFR4, S1PR1, HLA- DPB1, CD3E, HLA-DOA, HLA-DQB1, ICOSLG/LOC102723996, HLA-DOB, PIK3C2B, SPI1, JAG2, TYK2, VAV1, HLA-DRA, IL25, IL10, IL4R, CD247, TBX21, IL12RB1 IRF1, LGALS9, HLA-DQA2, PIK3R6, HLA-DQA1, SOCS3, JAK3, PIK3R5, ITGB2, IL27, DLL4, IL10RA, HLA-DQB2, CD8A, HLA-DRB1, HLA-DMA, HLA-DRB5, Th1 Pathway 7.3 3.4 HLA-DMB, HLA-DPA1, CD4, FGFR4, HLA-DPB1, CD3E, HLA-DOA, HLA-DQB1, ICOSLG/LOC102723996, HLA-DOB, PIK3C2B, TYK2, VAV1, HLA-DRA, HAVCR2, CXCR3, IL10, SOCS1, CD247, TBX21, IL12RB1 Complement ITGAM, CFI, C3, C1QB, ITGAX, ITGB2, C6, C1R, C3AR1, C1QA, C1QC, MASP1, 6.2 2.7 System C5AR1, C1S, CFD, SERPING1 IRF1, MYD88, GAD1, HLA-DQA1, SOCS3, TNFRSF1A, FCER1G, NFKBIA, Type I Diabetes NFKBID, HLA-DRB1, TNF, HLA-DMA, HLA-DRB5, HLA-DMB, CD3E, HLA-E, 6.0 2.2 Mellitus Signalling FASLG, HLA-DOA, IL1B, TNFRSF1B, HLA-DQB1, PTPRN, PRF1, MAP3K14, HLA-DOB, TRADD, HLA-DRA, NFKB2, GAD2, SOCS1, CD247 SIGIRR, IL1RL1, CCL3, TLR7, NLRP12, MYD88, IL1B, NOD2, NLRC5, ITGAX, TREM1 Signalling 6.0 4.5 NFKB2, CD83, LAT2, FCGR2B, TNF, NLRP3, TYROBP, IL10, DEFB4A/DEFB4B, CXCL3, NLRP6, ITGA5, CIITA, MAPK3 PIK3R6, MYD88, HLA-DQA1, PLCB2, TNFRSF1A, PIK3R5, COL1A1, FCER1G, NFKBIA, TREM2, IL36A, NFKBID, CD83, IRF8, HLA-DRB1, TNF, RELB, HLA- Dendritic Cell DMA, HLA-DRB5, TYROBP, HLA-DMB, IGHG1, FGFR4, NOTUM, IGHG4, 5.6 4.5 Maturation MAPK3, IL32, HLA-DOA, IL1B, TNFRSF1B, HLA-DQB1, MAP3K14, HLA-DOB, PIK3C2B, PLCH1, HLA-DRA, NFKB2, FCGR2B, IGHG2, COL2A1, IL10, LEP, IGHG3, COL11A2 Neuroprotective KLK6, MMP9, PRSS33, TMPRSS11B, TPSG1, TPSAB1/TPSB2, PRSS21, ST14, Role of THOP1 in ACE, C1R, GZMK, HTRA3, PRSS57, TPSD1, KLK4, TMPRSS9, GZMM, PRSS36, 4.9 4.3 Alzheimer's SST, HLA-E, CTRL, APP, PNOC, PRSS22, CTSG, CMA1, MASP1, CTRB2, CTRB1, Disease CFD CXCL12, ITGAM, ITGAL, PIK3R6, CLDN7, MMP9, MMP2, NCF1, PIK3R5, TIMP4, Leukocyte ITGB2, THY1, RAC2, RAPGEF3, WAS, CLDN14, ICAM3, CLDN5, ITGB3, Extravasation 4.9 3.1 CLDN20, FGFR4, NCF4, SPN, SRC, MMP11, VASP, CD99, PIK3C2B, VAV1, Signalling RASSF5, ABL1, MMP3, PRKCA, PTK2B, ARHGAP8/PRR5-ARHGAP8, CLDN23, Ingenuity Time canonical -log (p-value) Z-score Genesa pathways SELPLG, ARHGAP4, BCAR1, MMP10, ITGA5, CYBA, ARHGAP9, MMP23B, MMP16 JUN, OSM, FTL, MYD88, C3, SOCS3, SAA4, TNFRSF1A, KLKB1, LBP, RBP4, Acute Phase C1R, NFKBIA, IL36A, NFKBID, HP, TNF, SERPINF2, VWF, HAMP, MAPK3, Response 4.3 3.5 TCF3, IL1B, TNFRSF1B, MAP3K14, ITIH3, RBP1, TRADD, HMOX1, NFKB2, Signalling SOD2, CEBPB, SERPINA1, SOCS1, C1S, SERPING1, RRAS JUN, PIK3R6, HLA-DQA1, PIK3R5, MAP3K10, CACNA1B, FCER1G, RAC2, NFKBIA, NFKBID, CARD11, HLA-DRB1, HLA-DMA, HLA-DRB5, LCK, HLA- PKCθ Signalling in 3.9 4.9 DMB, CD4, FGFR4, ZAP70, MAPK3, CD3E, HLA-DOA, HLA-DQB1, MAP3K14, T Lymphocytes HLA-DOB, PIK3C2B, CACNA1A, VAV1, HLA-DRA, NFKB2, CACNG7, CD247, RRAS, CACNG4 Calcium-induced T CD3E, ATP2A3, HLA-DOA, HLA-DQA1, HLA-DQB1, HLA-DOB, FCER1G, HLA- Lymphocyte 3.6 3.6 DRA, HLA-DRB1, PRKCA, HLA-DMA, HLA-DRB5, LCK, HLA-DMB, CD4, Apoptosis MEF2D, CD247, ZAP70 JUN, PIK3R6, HLA-DQA1, PIK3R5, FCER1G, NFKBIA, NFKBID, CARD11, SYK, CD28 Signalling in WAS, HLA-DRB1, HLA-DMA, HLA-DRB5, LCK, ARPC4, HLA-DMB, CD4, 3.6 2.8 T Helper Cells PTPN6, FGFR4, ZAP70, CD3E, HLA-DOA, HLA-DQB1, HLA-DOB, PIK3C2B, VAV1, HLA-DRA, NFKB2, CD247 PIK3R6, HLA-DQA1, PIK3R5, IL2RB, FCER1G, NFKBIA, NFKBID, IL2RG, iCOS-iCOSL INPP5D, HLA-DRB1, HLA-DMA, HLA-DRB5, LCK, HLA-DMB, CD4, FGFR4, Signalling in T 3.4 3.8 ZAP70, CD3E, HLA-DOA, HLA-DQB1, ICOSLG/LOC102723996, HLA-DOB, Helper Cells PIK3C2B, VAV1, HLA-DRA, NFKB2, CD247 PIK3R6, TGFB1, HLA-DQA1, TNFRSF1A, TICAM1, JAK3, PIK3R5, KCNJ9, SLC6A12, SYK, HLA-DRB5, TYROBP, GRIN2D, FGFR4, TLR7, CCL5, IL1B, HLA- DQB1, CALB2, BIRC5, APP, HLA-DOB, PIK3C2B, HLA-DRA, NFKB2, SOD2, Neuroinflammation 3.2 4.7 GDNF, MMP3, KCNJ5, IL10, PLA2G2A, PLA2G2D, JUN, CXCL12, MMP9, Signalling Pathway MYD88, GAD1, TREM2, CSF1R, MAPK4, HLA-DRB1, TNF, HLA-DMA, HLA- DMB, MAPK7, MAPK3, CCL3, FASLG, HLA-DOA, TYK2, HMOX1, GRIN2B, NLRP3, GAD2 JUN, IL1RL1, PIK3R6, SOCS3, TNFRSF1A, PIK3R5, COL1A1, LBP, NFKBIA, IL-6 Signalling 3.1 3.0 IL36A, NFKBID, MAPKAPK2, HSPB2, TNF, HSPB7, FGFR4, MAPK3, MAP4K4, IL1B, TNFRSF1B, CD14, MAP3K14, PIK3C2B, NFKB2, CEBPB, SOCS1, RRAS Ingenuity Time canonical -log (p-value) Z-score Genesa pathways Role of Pattern EIF2S1, OSM, PIK3R6, MYD88, C3, TGFB1, TICAM1, PIK3R5, C3AR1, C1QA, Recognition SYK, TNF, C5AR1, FGFR4, MAPK3, TLR7, CCL5, IL1B, NOD2, C1QB, PIK3C2B, Receptors in NFKB2, C1QC, PRKCA, IL25, NLRP3, IL10, CLEC7A 3.0 3.4 Recognition of Bacteria and Viruses JUN, ITGAM, AZU1, PIK3R6, GPLD1, MMP9, MMP2, PLCB2, PLD3, LIMK1, PIK3R5, ITGB2, LASP1, ARRB2, RAC2, GNG4, ITGB3, ANGPT1, FGFR4, MAPK3, IL-8 Signalling 2.7 3.4 MAP4K4, SRC, CCND2, VASP, ITGAX, CSTB, PIK3C2B, PLD4, HMOX1, RHOG, EGF, PRKCA, PTK2B, PLD2, RHOF, RRAS Fcγ Receptor- HCK, SRC, GPLD1, VASP, PLD3, NCF1, FGR, PLD4, RAC2, HMOX1, VAV1, SYK, mediated WAS, INPP5D, PRKCA, PTK2B, ARPC4, PLD2, RAB11B, MAPK3 Phagocytosis in 2.5 3.6 Macrophages and Monocytes JUN, PIK3R6, PIK3R5, MAP3K10, CD22, RAC2, NFKBIA, NFKBID, SYK, INPP5D, B Cell Receptor APBB1IP, IGHG1, RAP2B, PTPN6, FGFR4, CD79A, IGHG4, MAPK3, TCF3, 2.4 3.5 Signalling MAP3K14, PIK3C2B, EGR1, IGHA1, VAV1, RASSF5, CFL2, NFKB2, ABL1, FCGR2B, IGHG2, PTK2B, IGHE, IGHG3, RRAS JUN, PIK3R6, HLA-DQA1, PLCB2, PIK3R5, CSNK1G2, FCER1G, NFKBIA, Role of NFAT in NFKBID, SYK, HLA-DRB1, HLA-DMA, HLA-DRB5, LCK, GNG4, HLA-DMB, Regulation of the 2.3 5.0 CD4, FGFR4, MEF2D, CD79A, ZAP70, MAPK3, CD3E, HLA-DOA, HLA-DQB1, Immune Response HLA-DOB, PIK3C2B, HLA-DRA, NFKB2, FCGR2B, CD247, RRAS, GNA15 Production of Nitric JUN, IRF1, PPP1R14A, PIK3R6, SAA4, TNFRSF1A, NCF1, JAK3, PIK3R5, Oxide and Reactive MAP3K10, RBP4, APOC1, NFKBIA, NFKBID, IRF8, PPP1R3C, TNF, PTPN6, 2.3 4.2 Oxygen Species in FGFR4, MAPK3, NCF4, TNFRSF1B, MAP3K14, PIK3C2B, SPI1, TYK2, RHOG, Macrophages NFKB2, LYZ, PRKCA, SERPINA1, APOE, RHOF, CYBA JUN, PIK3R6, MMP9, MMP2, TGFB1, TNFRSF1A, FZD2, JAK3, PIK3R5, WNT11, Colorectal Cancer WNT2, MSH6, TNF, GNG4, LRP1, FGFR4, MAPK3, ADCY4, TLR7, TCF3, SRC, Metastasis 2.2 4.4 MMP11, ADCY7, WNT5B, BIRC5, PIK3C2B, PTGER4, TYK2, DVL1, RALGDS, Signalling RHOG, NFKB2, GRK2, EGF, MMP3, MMP10, RHOF, RRAS, MMP23B, MMP16, WNT9A Ingenuity Time canonical -log (p-value) Z-score Genesa pathways NF-κB Activation ITGAL, TNFRSF14, PIK3R6, MAP3K14, PIK3R5, PIK3C2B, ITGB2, NFKBIA, 2.2 2.8 by Viruses NFKBID, NFKB2, PRKCA, LCK, CD4, ITGB3, FGFR4, ITGA5, RRAS, MAPK3 JUN, PIK3R6, JAK3, PIK3R5, IL2RB, PIK3C2B, IL2RG, SYK, PTK2B, LCK, SOCS1, IL-2 Signalling 2.0 2.5 FGFR4, RRAS, MAPK3 PLA2G2D, ARHGEF15, PPP1R14A, GPLD1, PLCB2, PLD3, FCER1G, RAPGEF3, SYK, LCK, GNG4, IGHG1, MEF2D, CD79A, IGHG4, ZAP70, MAPK3, ADCY4, Phospholipase C 2.0 4.5 CD3E, SRC, ADCY7, PLD4, HMOX1, MYL10, RALGDS, RHOG, NFKB2, FCGR2B, Signalling PRKCA, IGHG2, ARHGEF1, MYLPF, PLD2, IGHG3, RHOF, CD247, ITGA5, RRAS, PLA2G2A PIK3R6, SOCS3, TNFRSF1A, PIK3R5, CACNA1B, NFKBIA, ADIPOQ, NFKBID, Type II Diabetes GCK, TNF, FGFR4, MAPK3, IRS4, TNFRSF1B, MAP3K14, PIK3C2B, TRADD, 1.9 2.5 Mellitus Signalling CACNA1A, ENPP7, NFKB2, CACNG7, PRKCA, SLC2A4, CEBPB, ACSL3, SOCS1, CACNG4 PLA2G2D, IL1RL1, FASLG, TGFB1, IL1B, TNFRSF1B, TNFRSF1A, MAP4K1, p38 MAPK 1.9 2.9 HMGN1, TRADD, IL36A, RPS6KA6, MAPKAPK2, HSPB2, DUSP1, TNF, HSPB7, Signalling RPS6KA2, RPS6KA1, MEF2D, PLA2G2A, RPS6KA4 Toll-like Receptor JUN, SIGIRR, IL1RL1, MAP4K4, TLR7, MYD88, IL1B, CD14, TICAM1, MAP3K14, 1.7 2.3 Signalling LBP, NFKBIA, IL36A, NFKB2, TNF Glioma PIK3R6, MMP9, PLAU, MMP2, PLAUR, PIK3R5, TIMP4, PIK3C2B, RHOG, ITGB3, Invasiveness 1.7 2.1 FGFR4, RHOF, RRAS, MAPK3 Signalling iNOS Signalling 1.6 2.8 JUN, IRF1, NFKB2, MYD88, CD14, JAK3, LBP, TYK2, NFKBIA, NFKBID Pancreatic E2F5, PIK3R6, GPLD1, MMP9, TGFB1, PLD3, BIRC5, JAK3, PIK3R5, PIK3C2B, Adenocarcinoma 1.6 2.2 PLD4, TYK2, HMOX1, RALGDS, NFKB2, ABL1, EGF, E2F8, PLD2, FGFR4, Signalling MAPK3 JUN, PIK3R6, SRC, LPAR2, CDH12, CDH4, PIK3R5, PIK3C2B, NFKBIA, VAV1, Gα12/13 Signalling 1.6 3.3 MYL10, NFKBID, NFKB2, PTK2B, LPAR5, ARHGEF1, MYLPF, MAPK7, CDH23, FGFR4, MEF2D, RRAS, MAPK3 IL1RL1, MMP9, TGFB1, TNFRSF1A, FZD2, ITLN1, RBP4, RARRES2, ELF3, Osteoarthritis ADIPOQ, PTCH2, GLIS1, TNF, LRP1, SPP1, GLIS2, TCF3, IL1B, TNFRSF1B, H19, 1.5 3.4 Pathway ACVRL1, PRG4, NFKB2, ALPL, MMP3, CEBPB, MMP10, COL2A1, EPAS1, C1QTNF4, LEP, FRZB, ITGA5 Ingenuity Time canonical -log (p-value) Z-score Genesa pathways Oncostatin M MMP3, OSM, PLAU, JAK3, EPAS1, TYK2, RRAS, MAPK3 1.5 2.6 Signalling SH2D3C, ARHGEF15, CXCL12, LIMK1, PDGFB, RAC2, PAK3, WAS, ARPC4, Ephrin Receptor 1.5 3.1 GNG4, GRIN2D, ANGPT1, PTPN13, RAPGEF1, MAPK3, DOK1, MAP4K4, SRC, Signalling MAP3K14, EPHB2, CFL2, GRIN2B, ABL1, EGF, BCAR1, ITGA5, RRAS, GNA15 MIF-mediated PLA2G2D, NFKB2, CD74, CD14, NFKBIA, NFKBID, PLA2G2A, MAPK3 Glucocorticoid 1.5 2.8 Regulation JUN, PDGFRB, PIK3R6, SRC, JAK3, PIK3R5, PIK3C2B, PDGFB, TYK2, ABL1, PDGF Signalling 1.4 3.0 INPP5D, PRKCA, SPHK2, FGFR4, RRAS, MAPK3 TNFR2 Signalling 1.4 2.4 JUN, NFKB2, TNFRSF1B, TNF, MAP3K14, NFKBIA, NFKBID MIF Regulation of PLA2G2D, JUN, NFKB2, CD74, CD14, NFKBIA, NFKBID, PLA2G2A, MAPK3 1.4 3.0 Innate Immunity PIK3R6, MYD88, TNFRSF1A, PIK3R5, FCER1G, NFKBIA, IL36A, NFKBID, CARD11, TNF, RELB, LCK, NTRK3, FGFR4, ZAP70, SIGIRR, PDGFRB, MAP4K4, NF-κBSignalling 1.3 3.0 TLR7, IL1B, TNFRSF1B, MAP3K14, PIK3C2B, TRADD, IGF1R, NFKB2, EGF, RRAS PLA2G2D, GPLD1, PLCB2, CSF2RB, PLD3, SLC2A8, PLD4, NFKBIA, PLCH1, Antioxidant Action 1.8 -2.7 HMOX1, NFKBID, SLC2A5, NFKB2, SLC2A4, TNF, PLD2, NOTUM, PLA2G2A, of Vitamin C PLA2G2C, MAPK3 JUN, IL1RL1, PDGFRB, MAP4K4, IL1B, TNFRSF1B, TNFRSF1A, MAP3K14, PPAR Signalling 2.4 -2.7 PDGFB, NFKBIA, IL36A, NFKBID, CITED2, NFKB2, TNF, NR1H3, HSP90AB1, HSP90AA1, RRAS, MAPK3 Week IRF1, LGALS9, HLA-DQA2, PIK3R6, IFNG, SOCS3, HLA-DQA1, JAK3, PIK3R5, 12 ITGB2, IL6, CD40, GAB1, CD274, IL27, HLA-DQB2, IL10RA, CCR5, CD8A, HLA- DRB1, HLA-DMA, HLA-DRB5, HLA-DPA1, HLA-DMB, GRB2, CD80, CD4, Th1 Pathway 13.7 3.7 PIK3C3, HLA-DPB1, CD3E, HLA-DOA, HLA-DQB1, CD3G, ICOSLG/LOC102723996, VAV1, HLA-DRA, HAVCR2, KLRD1, CXCR3, IL10, SOCS1, HLA-B, CD247, TBX21, IL12RB1 IL3, HLA-DQA2, PIK3R6, IFNG, TGFB1, CCR1, SOCS3, HLA-DQA1, JAK3, Th2 Pathway 13.1 2.6 PIK3R5, IL2RB, ITGB2, CD40, GAB1, IL2RG, HLA-DQB2, IKZF1, CXCR6, CCR5, Ingenuity Time canonical -log (p-value) Z-score Genesa pathways CXCR4, HLA-DRB1, HLA-DMA, HLA-DRB5, HLA-DPA1, HLA-DMB, GRB2, CD80, CD4, CRLF2, PIK3C3, HLA-DPB1, CD3E, HLA-DOA, HLA-DQB1, CD3G, ICOSLG/LOC102723996, SPI1, MAF, VAV1, HLA-DRA, TNFSF4, IL4R, IL10, HLA-B, CD247, TBX21, IL12RB1 FCGR1B, PIK3R6, CSF2, HLA-DQA1, PLCB2, FCGR1A, TNFRSF1A, PIK3R5, FCER1G, NFKBIA, IRF8, RELB, TYROBP, HLA-DRB5, CD80, TLR2, PIK3C3, Dendritic Cell IL32, IL1B, HLA-DQB1, TNFRSF1B, PLCH1, HLA-DRA, NFKB2, CREB5, IL10, 11.0 4.6 Maturation HLA-C, HLA-B, IKBKE, IL15, AKT3, MYD88, IL6, CD40, GAB1, TREM2, CD83, HLA-DRB1, TNF, HLA-DMA, HLA-DMB, GRB2, IGHG1, CREB3L3, IGHG4, HLA- DOA, FCGR2B, MAPK13, COL2A1, IGHG3, DDR2 NLRP12, CSF2, AKT3, MYD88, NLRC5, IL6, CD40, CD83, TLR8, TNF, TYROBP, TREM1 Signalling 10.9 5.0 GRB2, TREM1, TLR2, CIITA, CCL3, CCL7, TLR7, IL1B, NOD2, ITGAX, NFKB2, LAT2, FCGR2B, CCL2, IL10, DEFB4A/DEFB4B, CXCL3, NLRP6 PIK3R6, TGFB1, HLA-DQA1, TNFRSF1A, JAK3, TICAM1, PIK3R5, NCF2, FOS, TLR8, SLC6A12, SYK, TYROBP, HLA-DRB5, GRIN2D, CD80, BIRC7, GRIN3A, TLR2, PLA2G4A, PIK3C3, TLR7, CCL5, IL1B, HLA-DQB1, APP, WNT1, HLA- Neuroinflammation DRA, NFKB2, SOD2, GDNF, MMP3, CREB5, KCNJ5, IL10, HLA-C, HLA-B, CYBB, 10.3 5.5 Signalling Pathway IKBKE, PLA2G2D, AKT3, IFNG, MMP9, MYD88, GAD1, IL6, CD40, GAB1, TREM2, CSF1R, MAPK4, HLA-DRB1, TNF, HLA-DMA, HLA-DMB, GRB2, CREB3L3, CCL3, FASLG, HLA-DOA, GABRG2, HMOX1, GABRG1, PYCARD, GRIN2B, CCL2, MAPK13, GAD2 Role of Pattern MBL2, EIF2S1, IL3, OSM, PIK3R6, CSF2, IFNG, TGFB1, MYD88, TICAM1, Recognition PIK3R5, IL6, GAB1, C3AR1, C1QA, TLR8, SYK, TNF, C5AR1, GRB2, IL17C, TLR2, Receptors in PIK3C3, PTX3, TLR7, CCL5, IL1B, NOD2, PRKD3, C1QB, NFKB2, C1QC, PRKCA, 7.9 2.2 Recognition of IL10, PRKD1, CLEC7A Bacteria and Viruses PIK3R6, AKT3, HLA-DQA1, PIK3R5, IL2RB, FCER1G, CD40, GAB1, NFKBIA, iCOS-iCOSL IL2RG, INPP5D, HLA-DRB1, HLA-DMA, LCK, HLA-DRB5, HLA-DMB, GRB2, Signalling in T 6.5 3.5 CD80, CD4, PIK3C3, CD3E, HLA-DOA, HLA-DQB1, CD3G, Helper Cells ICOSLG/LOC102723996, VAV1, HLA-DRA, NFKB2, HLA-B, CD247, IKBKE Ingenuity Time canonical -log (p-value) Z-score Genesa pathways Production of Nitric IRF1, PIK3R6, AKT3, IFNG, TNFRSF1A, JAK3, NCF1, PIK3R5, APOC1, GAB1, Oxide and Reactive NFKBIA, NCF2, FOS, IRF8, TNF, MAP3K8, GRB2, PTPN6, TLR2, PIK3C3, NCF4, 5.6 3.2 Oxygen Species in TNFRSF1B, PRKD3, ORM2, SPI1, RHOJ, NFKB2, RHOG, LYZ, PRKCA, ORM1, Macrophages MAPK13, SERPINA1, PRKD1, CYBB, RHOF, RHOU, CYBA, IKBKE, RND2 Calcium-induced T CD3E, HLA-DOA, HLA-DQB1, CD3G, HLA-DQA1, PRKD3, FCER1G, HLA-DRA, Lymphocyte 5.1 2.8 HLA-DRB1, PRKCA, HLA-DMA, LCK, HLA-DRB5, HLA-DMB, CD4, PRKD1, Apoptosis HLA-B, MEF2D, CD247 ITGAM, ITGAL, PIK3R6, MMP9, MMP12, NCF1, PIK3R5, ITGB2, WIPF1, GAB1, Leukocyte RAC2, CLDN2, NCF2, WAS, CXCR4, DLC1, GRB2, ITGB3, PIK3C3, NCF4, SPN, Extravasation 4.7 2.3 PRKD3, ARHGAP5, VASP, PTK2, VAV1, RASSF5, CTNNA2, MMP3, PRKCA, Signalling PTK2B, MAPK13, SELPLG, ARHGAP4, MMP10, PRKD1, CYBB, CYBA, MMP1, ARHGAP9 FCGR1B, PIK3R6, AKT3, HLA-DQA1, PLCB2, FCGR1A, PIK3R5, FCER1G, GAB1, Role of NFAT in NFKBIA, FOS, SYK, HLA-DRB1, HLA-DMA, LCK, HLA-DRB5, HLA-DMB, Regulation of the 4.5 4.5 GRB2, CD80, CD4, MEF2D, PIK3C3, CD3E, HLA-DOA, HLA-DQB1, CD3G, Immune Response RCAN1, HLA-DRA, NFKB2, FCGR2B, HLA-B, GNG2, CD247, IKBKE, GNA15, LYN Role of IL-17F in CCL7, CSF2, IL1B, IL6, NFKB2, IL17RA, CREB5, RPS6KA2, CCL2, CXCL1, Allergic RPS6KA1, CREB3L3, CXCL5, CCL4 4.3 3.1 Inflammatory Airway Diseases MBL2, CFB, OSM, FTL, TF, AKT3, MYD88, SOCS3, TNFRSF1A, KLKB1, IL6, Acute Phase NFKBIA, FOS, C4A/C4B, FN1, C2, TNF, GRB2, IL1RAP, HAMP, IL1B, TNFRSF1B, Response 4.2 2.9 ORM2, HMOX1, NFKB2, SOD2, ORM1, CEBPB, MAPK13, SERPINA1, SOCS1, Signalling SERPING1, IKBKE PIK3R6, AKT3, IFNG, TGFB1, MMP9, TNFRSF1A, MMP12, JAK3, PIK3R5, IL6, Colorectal Cancer GAB1, FOS, TLR8, WNT8B, ADCY3, WNT2, TNF, GRB2, LRP1, LRP6, TLR2, Metastasis 4.1 2.9 PIK3C3, TLR7, ADCY7, PTGER4, WNT1, RHOJ, PTGER2, RALGDS, MSH3, Signalling NFKB2, RHOG, GRK2, EGF, MMP3, MYC, MMP10, GNG2, RHOF, RHOU, MMP1, MSH2, RND2 B Cell Receptor PIK3R6, AKT3, PIK3R5, CD22, GAB1, RAC2, NFKBIA, SYK, INPP5D, PIK3AP1, 3.9 2.6 Signalling MAP3K8, GRB2, IGHM, IGHG1, APBB1IP, CREB3L3, PTPN6, RAP2B, IGHG4, Ingenuity Time canonical -log (p-value) Z-score Genesa pathways PIK3C3, INPP5F, IGHA1, PTK2, VAV1, RASSF5, NFKB2, FCGR2B, CREB5, PTK2B, MAPK13, IGHE, IGHG3, POU2F2, IKBKE, LYN Fcγ Receptor- HCK, CSF2, AKT3, FCGR1A, PRKD3, VASP, PLD3, NCF1, FGR, RAC2, HMOX1, mediated VAV1, WAS, SYK, MYO5A, INPP5D, PRKCA, PTK2B, ARPC4, PRKD1, LYN Phagocytosis in 3.8 2.4 Macrophages and Monocytes IL3, OSM, PIK3R6, CSF2, AKT3, IFNG, TGFB1, TNFRSF1A, PIK3R5, IL6, GAB1, HMGB1 Signalling 3.5 2.7 FOS, TNF, GRB2, IL17C, PIK3C3, IL1B, TNFRSF1B, RHOJ, NFKB2, RHOG, CCL2, MAPK13, RHOF, RHOU, RND2 PIK3R6, HLA-DQA1, PIK3R5, FCER1G, GAB1, RAC2, NFKBIA, CARD11, FOS, PKCθ Signalling in HLA-DRB1, HLA-DMA, LCK, MAP3K8, HLA-DRB5, HLA-DMB, GRB2, CD80, 3.31 3.9 T Lymphocytes CD4, PIK3C3, CD3E, HLA-DOA, HLA-DQB1, CD3G, VAV1, HLA-DRA, NFKB2, HLA-B, CD247, IKBKE Chemokine CCL7, CCL5, PLCB2, CCL24, LIMK1, PTK2, FOS, CCR5, CXCR4, PRKCA, PTK2B, 2.6 2.3 Signalling CCL2, MAPK13, CAMK1G, CCL4 iNOS Signalling 2.1 2.3 NFKB2, IRF1, FOS, IFNG, MYD88, CD14, JAK3, MAPK13, NFKBIA, IKBKE Inflammasome NFKB2, IL1B, MYD88, NOD2, CTSB, PYCARD 2.1 2.4 pathway PLA2G2D, FASLG, TGFB1, IL1B, TNFRSF1B, TNFRSF1A, MAP4K1, MAPKAPK2, p38 MAPK 1.7 2.2 MYC, CREB5, RPS6KA2, TNF, MAPK13, MKNK1, RPS6KA1, IL1RAP, CREB3L3, Signalling MEF2D, PLA2G4A AKAP3, PDE4A, PDE3B, PDE6G, FPR1, AGTR2, AKAP12, ADCY3, GRM4, cAMP-mediated PDE11A, P2RY13, GRM7, CREB3L3, PDE6B, AKAP6, DRD3, ADCY7, HTR1D, 1.6 2.7 Signalling AKAP2, FPR2, PDE1B, PTGER4, SSTR3, PTGER2, GRK2, CREB5, RGS14, RPS6KA1, ADORA3, CAMK1G, AKAP9 Death Receptor PARP12, CASP10, FASLG, TNFRSF1B, TNFSF15, TNFRSF1A, TNFSF12, PARP15, 1.5 2.8 Signalling LIMK1, NFKBIA, NFKB2, TNF, GAS2, ART1, IKBKE VDR/RXR CSF2, IFNG, CCL5, CD14, PRKD3, MED1, CAMP, CEBPA, PRKCA, CEBPB, 1.5 2.4 Activation PRKD1, NCOR1, CYP24A1 Ingenuity Time canonical -log (p-value) Z-score Genesa pathways Oncostatin M CHI3L1, MMP3, OSM, PLAU, JAK3, GRB2, MMP1 1.4 2.6 Signalling aMolecules in the uploaded dataset included in the predefined IPA canonical pathways.