Table 1.
Consensus Pathway Data Base Analysis: Thirty-Eight Enriched Acute Respiratory Distress Syndrome Pathways
| Pathway name | Candidates contained | p-Value | Q-Value | Pathway source | Genes contained |
|---|---|---|---|---|---|
| Immunological pathways | |||||
| Immune system | 74 (4.1%) | 7.69e-17 | 1.29e-15 | Reactome | ACTG1, AGER, ARG1, ARPC4, B2M, C3, C9, CAP1, CAT, CCT8, CEACAM1, CEACAM8, CHIT1, COTL1, CRISP3, CSF2, CSF2RB, CYBA, DEFA4, DNAJC5, FABP5, FGA, FTH1, FTL, GBP2, GHR, GPI, GSTP1, HBB, HMGB1, HSP90AB1, HSPA1A, HSPA8, IL13, IL1B, IL1R2, IL1RN, IL4, IL6, ISG15, JUN, KEAP1, LCN2, LGALS3, MAP3K1, MIF, MMP8, MMP9, MUC5AC, NCF1, NOS3, OLFM4, OSM, PDIA3, PGAM1, PI3, PLAUR, PPIA, PRDX6, RNASE3, S100A12, S100A8, S100A9, SAA1, SERPINA1, TCN1, TLR1, TNF, TNFAIP3, TNFRSF11A, TTR, TXN, VASP, YWHAZ |
| Innate immune system | 58 (5.4%) | 1.05e-18 | 5.29e-17 | Reactome | ACTG1, AGER, ARG1, ARPC4, B2M, C3, C9, CAP1, CAT, CCT8, CEACAM1, CEACAM8, CHIT1, COTL1, CRISP3, CYBA, DEFA4, DNAJC5, FABP5, FGA, FTH1, FTL, GPI, GSTP1, HBB, HMGB1, HSP90AB1, HSPA1A, HSPA8, IL1B, ISG15, JUN, LCN2, LGALS3, MAP3K1, MIF, MMP8, MMP9, MUC5AC, NCF1, NOS3, OLFM4, PGAM1, PI3, PLAUR, PPIA, PRDX6, RNASE3, S100A12, S100A8, S100A9, SAA1, SERPINA1, TCN1, TLR1, TNFAIP3, TTR, TXN |
| Neutrophil degranulation | 41 (8.5%) | 7.87e-20 | 7.94e-18 | Reactome | ARG1, B2M, C3, CAP1, CAT, CCT8, CEACAM1, CEACAM8, CHIT1, COTL1, CRISP3, CYBA, DEFA4, DNAJC5, FABP5, FTH1, FTL, GPI, GSTP1, HBB, HMGB1, HSP90AB1, HSPA1A, HSPA8, LCN2, LGALS3, MIF, MMP8, MMP9, OLFM4, PGAM1, PLAUR, PPIA, PRDX6, RNASE3, S100A12, S100A8, S100A9, SERPINA1, TCN1, TTR |
| Cytokine signaling in the immune system | 21 (4.6%) | 5.64e-06 | 1.73e-05 | Reactome | AGER, B2M, CSF2, CSF2RB, GBP2, GHR, HMGB1, IL13, IL1B, IL1R2, IL1RN, IL4, IL6, ISG15, JUN, OSM, S100A12, SAA1, TNF, TNFRSF11A, YWHAZ |
| Signaling by interleukins | 15 (5.9%) | 6.95e-06 | 2.06e-05 | Reactome | AGER, CSF2, CSF2RB, HMGB1, IL13, IL1B, IL1R2, IL1RN, IL4, IL6, JUN, OSM, S100A12, SAA1, YWHAZ |
| Interleukin-4 and 13 signaling | 15 (15.3%) | 1.67e-11 | 1.3e-10 | Wikipathways | ANXA1, CCL2, CDKN1A, CEBPD, CXCL8, HSPA8, IL1B, IL6, LCN2, MMP9, OSM, PTGS2, S1PR1, SAA1, TNF |
| Interleukin 10 signaling | 10 (26.3%) | 1.57e-10 | 1.06e-09 | Wikipathways | CCL2, CSF2, CXCL2, CXCL8, IL1B, IL1R2, IL1RN, IL6, PTGS2, TNF |
| Interleukin 1 signaling | 7 (11.7%) | 3.12e-05 | 7.32e-05 | Reactome | AGER, HMGB1, IL1B, IL1R2, IL1RN, S100A12, SAA1 |
| Development and heterogeneity of the ILC family | 7 (21.9%) | 4.02e-07 | 2.51e-06 | Wikipathways | AHR, AREG, IL13, IL1B, IL4, IL6, TNF |
| Reactive oxygen species (ROS)-related pathways | |||||
| Cellular response to external stimuli | 26 (6.3%) | 6.14e-10 | 3.65e-09 | Reactome | CAT, CDKN1A, CEBPB, CXCL8, CYBA, CYCS, DNAJA1, DNAJB6, EPAS1, GSR, GSTP1, HSP90AB1, HSPA1A, HSPA8, IL6, JUN, NCF1, NOX4, PRDX2, PRDX3, PRDX5, PRDX6, PRKAG2, SOD2, SOD3, TXN |
| Cellular responses to stress | 25 (7.3%) | 6.59e-11 | 4.75e-10 | Reactome | CAT, CDKN1A, CEBPB, CXCL8, CYBA, CYCS, DNAJA1, DNAJB6, EPAS1, GSR, GSTP1, HSP90AB1, HSPA1A, HSPA8, IL6, JUN, NCF1, NOX4, PRDX2, PRDX3, PRDX5, PRDX6, SOD2, SOD3, TXN |
| Detoxification of reactive oxygen species | 14 (38.9%) | 5.52e-17 | 1.29e-15 | Reactome | CAT, CYBA, CYCS, GSR, GSTP1, NCF1, NOX4, PRDX2, PRDX3, PRDX5, PRDX6, SOD2, SOD3, TXN |
| Focal adhesion | 13 (6.3%) | 1.51e-05 | 4.01e-05 | Wikipathways | ACTG1, COL1A1, COL3A1, COL5A1, EGF, EGFR, FLNA, FLT1, ITGA1, JUN, MYLK, VASP, VWF |
| Toll-like receptor cascades | 10 (6.5%) | 0.000112 | 0.000242 | Reactome | AGER, FGA, HMGB1, JUN, MAP3K1, S100A12, S100A8, S100A9, SAA1, TLR1 |
| Oxidative stress | 9 (30.0%) | 3.63e-10 | 2.29e-09 | Wikipathways | CAT, CYBA, CYP1A1, GCLC, GSR, NFE2L2, NOX4, SOD2, SOD3 |
| Cardiovascular and signaling pathways | |||||
| Hemostasis | 27 (4.0%) | 2.58e-06 | 9.29e-06 | Reactome | ANXA5, APOA1, CAP1, CEACAM1, CEACAM8, EGF, F3, FGA, FLNA, GYPA, GYPB, HRG, ITGA1, JMJD1C, MIF, NOS3, PFN1, PLAUR, PPIA, PRKAR2A, SELPLG, SERPINA1, SERPINE1, TGFB2, TMSB4X, VWF, YWHAZ |
| VEGFA-VEGFR2 signaling pathway | 23 (9.7%) | 1.01e-12 | 9.31e-12 | Wikipathways | ANXA1, CCL2, CXCL8, DNAJB9, EZR, F3, FGA, GJA1, HBEGF, HSPA1A, JUN, MYH9, NCF1, NOS3, NR4A1, NR4A2, NR4A3, PFN1, PLAUR, PTGS2, SOD2, TXN |
| MAPK signaling pathway | 15 (6.1%) | 4.71e-06 | 1.59e-05 | Wikipathways | EGF, EGFR, FLNA, GADD45A, HSPA1A, HSPA8, IL1B, IL1R2, JUN, MAP3K1, MAP3K6, NR4A1, STMN1, TGFB2, TNF |
| Platelet activation, signaling, and aggregation | 15 (5.8%) | 9.2e-06 | 2.58e-05 | Reactome | ANXA5, APOA1, CAP1, EGF, FGA, FLNA, HRG, PFN1, PPIA, SERPINA1, SERPINE1, TGFB2, TMSB4X, VWF, YWHAZ |
| Platelet degranulation | 14 (10.9%) | 8.35e-09 | 4.68e-08 | Reactome | ANXA5, APOA1, CAP1, EGF, FGA, FLNA, HRG, PFN1, PPIA, SERPINA1, SERPINE1, TGFB2, TMSB4X, VWF |
| Response to elevated platelet cytosolic Ca2+ | 14 (10.4%) | 1.37e-08 | 7.28e-08 | Reactome | ANXA5, APOA1, CAP1, EGF, FGA, FLNA, HRG, PFN1, PPIA, SERPINA1, SERPINE1, TGFB2, TMSB4X, VWF |
| Adipogenesis | 13 (9.9%) | 8.49e-08 | 4.08e-07 | Wikipathways | ADIPOQ, AGT, AHR, CDKN1A, CEBPB, CEBPD, EPAS1, GADD45A, IL6, MIF, NAMPT, OSM, SERPINE1, TNF |
| Focal adhesion-PI3K-Akt-mTOR-signaling pathway | 13 (4.3%) | 0.000645 | 0.00113 | Wikipathways | CDKN1A, COL1A1, COL3A1, COL5A1, EGF, EGFR, EPAS1, FLT1, GHR, HSP90AB1, NOS3, OSM, VWF |
| PI3K-Akt signaling pathway | 13 (3.8%) | 0.0019 | 0.00309 | Wikipathways | CDKN1A, COL1A1, EGF, EGFR, FLT1, GHR, HSP90AB1, IL4, IL6, ITGA1, NOS3, OSM, VWF |
| AGE-RAGE | 9 (13.6%) | 5.88e-07 | 3.5e-06 | Wikipathways | AGER, CYCS, EGFR, EZR, JUN, LGALS3, MMP9, NCF1, NOS3 |
| Complement and coagulation cascades | 7 (11.9%) | 2.79e-05 | 7.04e-05 | Wikipathways | C3, C9, F3, PLAUR, SERPINA1, SERPINE1, VWF |
| Transcription factor and signaling pathways | |||||
| Nuclear receptors meta-pathway | 31 (9.8%) | 6.42e-17 | 1.29e-15 | Wikipathways | ABCB1, AGER, AHR, APOA1, CCL2, CYP1A1, EGFR, FTH1, FTL, GCLC, GCLM, GSR, GSTP1, HBEGF, HSP90AB1, HSPA1A, IL1B, JUN, KEAP1, NFE2L2, PDE4B, PLK2, PRDX6, PTGS2, SERPINA1, SOD3, TGFB2, TNF, TNFAIP3, TXN, UGT2B7 |
| NFR2 pathway | 18 (12.7%) | 3.98e-12 | 3.35e-11 | Wikipathways | AGER,FTH1, FTL, GCLC, GCLM, GSR, GSTP1, HBEGF, HSP90AB1, HSPA1A, KEAP1, NFE2L2, PRDX6, SERPINA1, SOD3, TGFB2, TXN, UGT2B7 |
| Vesicle-mediated transport | 18 (2.9%) | 0.00588 | 0.00843 | Reactome | AGTR1, APOA1, AREG, ARPC4, COL1A1, COL3A1, EGF, EGFR, FTH1, FTL, GJA1, HBB, HPX, HSPA8, PRKAG2, SAA1, SERPINA1, YWHAZ |
| G alpha (i) signaling events | 16 (4.0%) | 0.000347 | 0.000674 | Reactome | AGT, ANXA1, APOA1, C3, CXCL2, CXCL8, CXCR4, GRM3, HSPG2, PDE4B, PRKAR2A, RBP4, S1PR1, S1PR3, SAA1, TTR |
| Transcriptional regulation by TP53 | 13 (3.5%) | 0.00403 | 0.00598 | Reactome | BTG2, CDKN1A, CYCS, GADD45A, GPI, GSR, JUN, PLK2, PRDX2, PRDX5, PRKAG2, TXN, YWHAZ |
| Photodynamic therapy-induced NF-kB survival signaling | 8 (22.9%) | 3.83e-08 | 1.93e-07 | Wikipathways | CSF2, CXCL2, CXCL8, IL1B, IL6, MMP9, PTGS2, TNF |
| Other pathways | |||||
| Selenium micronutrient network | 19 (22.9%) | 1.1e-17 | 3.69e-16 | Wikipathways | APOA1, CAT, CBS, CCL2, GSR, HBB, IL1B, IL6, MTHFR, PRDX2, PRDX3, PRDX5, PTGS2, SAA1, SERPINE1, SOD2, SOD3, TNF, TXN |
| Spinal cord injury | 20 (17.1%) | 6.47e-16 | 9.33e-15 | Wikipathways | ANXA1, AQP1, ARG1, BTG2, CCL2, CXCL2, CXCL8, EGFR, GADD45A, GJA1, IL1B, IL4, IL6, LGALS3, MIF, MMP9, NOX4, NR4A1, PTGS2, TNF |
| Lung fibrosis | 14 (21.9%) | 4.82e-13 | 5.41e-12 | Wikipathways | CCL2, CEBPB, CSF2, CXCL2, CXCL8, EGF, IL13, IL1B, IL4, IL6, MMP9, NFE2L2, SERPINA1, TNF |
| Folate metabolism | 14 (21.2%) | 7.59e-13 | 7.67e-12 | Wikipathways | APOA1, CAT, CBS, CCL2, HBB, IL1B, IL4, IL6, MTHFR, SAA1, SERPINE1, SOD2, SOD3, TNF |
| Vitamin B12 metabolism | 13 (25.5%) | 3.99e-13 | 5.04e-12 | Wikipathways | APOA1, CBS, CCL2, HBB, IL1B, IL6, MTHFR, SAA1, SERPINE1, SOD2, SOD3, TCN1, TNF |
| Sudden infant death syndrome (SIDS) susceptibility pathways | 12 (7.5%) | 5.04e-06 | 1.63e-05 | Wikipathways | CEBPB, CXCL8, GJA1, HTR2A, IL13, IL1B, IL1RN, IL6, JUN, PRKAR2A, TNF, YWHAZ |
HMGB1, high mobility group box 1; KEAP1, Kelch-like ECH associated protein 1; MIF, macrophage migration inhibitory factor; MYLK, myosin light chain kinase; NAMPT, nicotinamide phosphoribosyl transferase; PRDXs, peroxiredoxin gene family; S1Ps, sphingosine 1-phosphate receptors.