Table 2.
List of pathways resulting from enrichment analysis of the network (Figure 4A) constructed upon the genes associated with the differentially methylated hypo- and hypermethylated promoters using the KEGG pathway database.
| KEGG Pathways | Tota | Expb | Hitsc | Pvald | FDRe | Seed genesf | Other genesg |
|---|---|---|---|---|---|---|---|
| Apoptosis | 136 | 7.91 | 31 | 2.56E-11 | 6.8E-10 | CASP7, TUBA8, CTSZ | DDIT3, BIRC2, TNFRSF1A, TRADD, IKBKG, RELA, NFKBIA, ACTB, XIAP, TP53, RAF1, CTSB, BIRC3, PIK3R1, FOS, NFKB1, FAS, AKT1, MAPK1, IKBKB, CTSD, TUBA1A, BCL2L11, TRAF2, ITPR3, JUN, FASLG, ACTG1 |
| NF-κB signaling pathway | 100 | 5.82 | 23 | 8.40E-09 | 1.03E-07 | ZAP70, TAB1 | TRAF6, UBE2I, BIRC2, TNFRSF1A, TRADD, IKBKG, NFKB2, RELA, NFKBIA, XIAP, BTK, IRAK1, MYD88, BIRC3, NFKB1, IKBKB, PLCG1, LCK, TRAF2, CSNK2B, LYN |
| Fluid shear stress and atherosclerosis | 139 | 8.08 | 26 | 8.57E-08 | 8.01E-07 | NQO1, GSTO2 | SUMO3, TNFRSF1A, IKBKG, RELA, CAV1, ACTB, TP53, HSP90AA1, SQSTM1, PIK3R1, CTNNB1, FOS, NFKB1, AKT1, SRC, PLAT, IKBKB, RAC1, SUMO1, SUMO2, HSP90AB1, VEGFA, JUN, ACTG1 |
| TNF signaling pathway | 110 | 6.4 | 22 | 2.55E-07 | 2.19E-06 | CASP7, TAB1, BCL3, DNM1L | BIRC2, TNFRSF1A, TRADD, IKBKG, RELA, NFKBIA, BIRC3, PIK3R1, FOS, NFKB1, FAS, AKT1, MAPK1, IKBKB, CREB1, TRAF2, CEBPB, JUN |
| Osteoclast differentiation | 128 | 7.44 | 23 | 1.01E-06 | 7.32E-06 | TAB1, LCP2, FHL2 | TRAF6, TNFRSF1A, IKBKG, NFKB2, RELA, NFKBIA, BTK, SQSTM1, PIK3R1, FOS, NFKB1, AKT1, GRB2, MAPK1, IKBKB, RAC1, CREB1, LCK, TRAF2, JUN |
| IL-17 signaling pathway | 93 | 5.41 | 19 | 1.20E-06 | 8.31E-06 | CSF3 | TRAF6, TRADD, IKBKG, RELA, NFKBIA, HSP90AA1, FOS, NFKB1, MAPK1, IKBKB, MAPK6, GSK3B, ELAVL1, S100A9, HSP90AB1, TRAF2, CEBPB, JUN |
| HIF-1 signaling pathway | 100 | 5.82 | 19 | 3.78E-06 | 2.36E-05 | LDHA | GAPDH, VHL, CREBBP, RELA, STAT3, ERBB2, EGFR, PIK3R1, NFKB1, HIF1A, AKT1, MAPK1, CDKN1A, EP300, CUL2, PLCG1, ENO3, VEGFA |
| Regulation of actin cytoskeleton | 214 | 12.4 | 29 | 1.56E-05 | 8.69E-05 | MYL2, PAK6, LIMK1, F2R, FGD1, FGD3 | MYL12A, ACTB, WAS, PPP1CA, RAF1, CRK, EGFR, PIK3R1, SRC, MAPK1, IQGAP1, SOS1, RAC1, CDC42, FN1, WASL, CRKL, PPP1CC, PAK2, GIT1, VAV2, ACTG1, ARHGEF7 |
| VEGF signaling pathway | 59 | 3.43 | 10 | 0.00192 | 0.00671 | NA | RAF1, PIK3R1, AKT1, SRC, MAPK1, RAC1, CDC42, PLCG1, PLA2G4A, VEGFA |
| TGFB signaling pathway | 92 | 5.35 | 13 | 0.00241 | 0.00817 | RGMA, RBL1, SMAD3, E2F4, HAMP | CREBBP, MYC, SMAD2, SMAD7, MAPK1, SP1, EP300, CUL1 |
“Tot” refers to the total number of genes that belong to the particular KEGG pathway as per the chosen reference list of genes, which is hg19 in our case,
“Exp” denotes the number of genes to be expected in our gene list for the particular KEGG pathway,
“Hits” describes the number of genes in our list that map to the particular KEGG pathway,
“Pval” is equivalent to the enrichment p-value computed using the hypergeometric test (see Methods),
“FDR” stands for false discovery rate, which is the method used to correct the corresponding p-value for multiple testing,
“Seed genes” represent genes associated with significantly differentially hyper- and hypomethylated promoters and
“Other genes” denote genes that are part of the minimum non-seed genes that are necessarily required to connect the seed genes to construct the network. The methylation direction of the seed genes can be found in Supplementary Table 1.