Supplementary Table S7.
(a) (i)
Canonical Pathways p-value Genes Mismatch Repair in Eukaryotes 1.349E-07 PCNA, MSH2, RFC4, MSH6, RFC2, SLC19A1, FEN1, RPA1, RFC5, POLD1, EXO1, RFC3 Role of CHK Proteins in Cell Cycle Checkpoint Control 6.310E-06 PPP2R3B, MDC1, RPA1, PLK1, RFC5, CDK1, RAD1, CHEK1, E2F6, PPP2R1A, PCNA, RFC4, CDKN1A, ATMIN, RFC2, SLC19A1, PPP2R2C, BRCA1, E2F2, RFC3, ATM, CDC25A Cell Cycle: G2/M DNA Damage Checkpoint Regulation 2.089E-05 PRKDC, YWHAG, CKS2, CCNB2, PLK1, CDK1, PRKCZ, SKP2, CHEK1, CCNB1, MDM4, TOP2B, CDKN1A, CKS1B, TOP2A, PKMYT1, BRCA1, ATM tRNA Charging 5.495E-05 RARS2, MARS2, GARS, LARS2, DARS2, QARS, MARS, NARS2, EPRS, EARS2, LARS, YARS, AARS2, AARS, VARS, IARS Mitotic Roles of Polo-Like Kinase 5.754E-05 ESPL1, CDC20, ANAPC1/ANAPC1P1, PTTG1, PRC1, CDC7, PPP2R3B, CCNB2, PLK1, CDK1, CCNB1, PPP2R1A, HSP90AB1, PLK2, CAPN1, ANAPC5, PKMYT1, HSP90AA1, FBXO5, PPP2R2C, KIF11, CDC25A Tetrahydrofolate Salvage from 5,10-methenyltetrahydrofolate 7.762E-05 MTHFD2, MTHFD1, MTHFD2L, MTHFD1L, GART Role of BRCA1 in DNA Damage Response 1.047E-04 RBL2, MDC1, RPA1, PLK1, RBL1, RFC5, FANCL, CHEK1, E2F6, FANCB, RFC4, MSH2, CDKN1A, MSH6, RFC2, SLC19A1, BLM, BRCA1, E2F2, RFC3, ATM Germ Cell-Sertoli Cell Junction Signaling 1.413E-04 EPN3, MAP3K11, TUBA3E, PIK3R1, ACTA2, HRAS, MAP3K4, TUBB, TGFBR2, PAK1, WASL, RHOB, TGFB2, PIK3R2, JUP, ACTG2, ATM, PXN, PAK2, NRAS, RHOC, TJP1, RRAS, TUBB4B, MAP3K1, ITGA2, TUBB2A, TUBG1, TUBA4A, RAC1, ITGA3, TUBA1B, RHOQ, TUBA1A, RND3, TGFB3, ZYX, MAP2K3, TUBA3C/TUBA3D, FNBP1, PVRL2 Cell Cycle Control of Chromosomal Replication 2.570E-04 MCM5, MCM3, RPA3, MCM2, CDK4, CDC6, ORC5, CDC7, CDK6, ORC6, RPA1, MCM7 Mechanisms of Viral Exit from Host Cells 4.266E-04 VPS28, SH3GL3, ACTA2, CHMP4B, VPS37C, TSG101, PRKCZ, CHMP6, CHMP2A, VPS36, LMNB2, PRKCH, ACTG2, PDCD6IP, CHMP3 Cell Cycle: G1/S Checkpoint Regulation 7.413E-04 RBL2, PA2G4, HDAC2, SUV39H1, PAK1IP1, SMAD3, CDK6, RBL1, CDKN2B, SKP2, E2F6, CDK4, CDKN1A, TGFB3, TGFB2, CDKN1B, E2F2, ATM, CDC25A GADD45 Signaling 8.710E-04 PCNA, GADD45B, CDK4, CDKN1A, MAP3K4, BRCA1, CDK1, CCNB1, ATM Hereditary Breast Cancer Signaling 9.333E-04 POLR2D, GADD45B, PIK3R1, HRAS, CHEK1, FANCB, XPC, RFC2, SLC19A1, PIK3R2, BLM, BRCA1, ATM, NRAS, HDAC2, RRAS, TUBG1, CDK6, RPA1, RFC5, CDK1, FANCL, CCNB1, MSH2, RFC4, CDK4, CDKN1A, MSH6, POLR2I, RFC3 Epithelial Adherens Junction Signaling 1.230E-03 EPN3, RAPGEF1, MYL6, TUBA3E, ACTA2, MYL5, BMPR2, HRAS, TUBB, TGFBR2, WASL, ARPC4, TGFB2, VCL, JUP, ACTG2, DLL1, NRAS, RRAS, TUBB4B, TUBG1, TUBB2A, ACVR1, RAC1, TUBA4A, TCF7L1, TUBA1B, TUBA1A, WAS, SNAI2, MYH9, SSX2IP, ZYX, LEF1, TUBA3C/TUBA3D, PVRL2 Estrogen-mediated S-phase Entry 1.549E-03 CCNA2, E2F6, CDK4, CDKN1A, CDKN1B, RBL1, CDK1, E2F2, SKP2, CDC25A Cyclins and Cell Cycle Regulation 1.778E-03 PA2G4, HDAC2, SUV39H1, CDK6, PPP2R3B, CCNB2, CDKN2B, CDK1, SKP2, CCNB1, E2F6, CCNA2, PPP2R1A, CDK4, CDKN1A, TGFB3, TGFB2, PPP2R2C, CDKN1B, E2F2, ATM, CDC25A Chronic Myeloid Leukemia Signaling 1.950E-03 PA2G4, BAD, SUV39H1, SMAD3, PIK3R1, HRAS, RBL1, TGFBR2, E2F6, TGFB2, CHUK, PIK3R2, E2F2, ATM, STAT5A, RBL2, NRAS, HDAC2, RRAS, CDK6, BCL2L1, CDK4, CDKN1A, TGFB3, CDKN1B Breast Cancer Regulation by Stathmin1 2.042E-03 CAMK1D, TUBA3E, PIK3R1, PPP1R3C, HRAS, PPP2R3B, GNG13, TUBB, PRKCZ, ROCK2, E2F6, GNB4, PAK1, STMN1, RB1CC1, PLCB1, PPP2R2C, PIK3R2, E2F2, ATM, ADCY9, CALML5, NRAS, RRAS, TUBB4B, TUBB2A, ADCY3, TUBG1, ADCY6, TUBA4A, RAC1, PPP1R11, TSG101, TUBA1B, CDK1, PPP2R1A, TUBA1A, ARHGEF16, ARHGEF6, CDKN1A, PRKCH, TUBA3C/TUBA3D, CDKN1B, CAMK2G Regulation of Cellular Mechanics by Calpain Protease 2.291E-03 CAPN5, PXN, NRAS, RRAS, ITGA2, CDK6, HRAS, ITGA3, CDK1, CCNA2, CAPN1, EZR, CDK4, CAPN9, CAST, VCL, CDKN1B D-glucuronate Degradation I 3.467E-03 AKR1A1, CRYL1, DCXR Protein Ubiquitination Pathway 4.898E-03 UBE2H, HSPA1A/HSPA1B, UBE2V2, DNAJC15, HSPA4, BAG1, UBE2D4, USP10, UCHL5, NEDD4L, PSMC2, BRCA1, PSMB5, DNAJC9, HSPA9, DNAJC25, PSMD3, SKP2, HSPA8, PSMB2, PSMD12, PSMB1, ANAPC5, HSP90AA1, PSMD1, TAP2, USP51, UBE2C, ANAPC1/ANAPC1P1, CDC20, DNAJC12, HSPA6, HSPB8, DNAJC10, DNAJA1, HSP90AB1, PSMD14, DNAJB1, AMFR, HSPA4L, HSPH1, USP30, PSMA1, HSPD1, USP1, DNAJB9, HSPA2, UBE2L6, PSMC1, DNAJC24, USP4, DNAJB11, PSMD2, USP37 Prostate Cancer Signaling 6.607E-03 NRAS, PA2G4, BAD, RRAS, SRD5A1, SUV39H1, NFKBIE, PIK3R1, HRAS, CREB3L4, NFKBIA, CASP9, HSP90AB1, CDKN1A, ATF4, HSP90AA1, LEF1, PIK3R2, CHUK, CDKN1B, ATM Actin Nucleation by ARP-WASP Complex 7.079E-03 NRAS, RHOC, RRAS, ITGA2, RAC1, HRAS, ITGA3, ROCK2, NCK2, WASL, RHOQ, RHOB, RND3, WAS, ARPC4, FNBP1 FAK Signaling 7.586E-03 CAPN5, PXN, NRAS, PAK2, ASAP1, RRAS, PIK3R1, HMMR, ACTA2, ITGA2, RAC1, HRAS, ITGA3, PAK1, WAS, CAPN1, ARHGEF6, CAPN9, PIK3R2, VCL, ACTG2, ATM NRF2-mediated Oxidative Stress Response 8.511E-03 PIK3R1, NQO2, ACTA2, DNAJA4, HSPB8, HRAS, DNAJC10, DNAJC15, DNAJA1, PRKCZ, GSTT1, AKR1A1, GSTM4, DNAJA3, ATF4, GCLM, DNAJB1, PIK3R2, ACTG2, FKBP5, GSTK1, ATM, GSTM1, NRAS, DNAJC9, RRAS, GSTM3, MAP3K1, NQO1, DNAJB9, TXNRD1, FOS, DNAJB11, CCT7, MAP2K3, PRKCH, ABCC4, ENC1, FTH1 Integrin Signaling 8.710E-03 RAPGEF1, MAP3K11, PIK3R1, ACTA2, MYL5, HRAS, NCK2, PAK1, WASL, RHOB, ARF4, GRB7, ARPC4, ACTG2, VCL, PIK3R2, TSPAN4, ATM, CAPN5, PXN, PARVA, TSPAN5, PAK2, NRAS, ASAP1, RRAS, RHOC, ITGA2, RALB, RAC1, BCAR3, ITGA3, MYL12A, RHOQ, RND3, WAS, MYL12B, CAPN1, ZYX, CAPN9, CTTN, FNBP1 Agrin Interactions at Neuromuscular Junction 8.913E-03 GABPB1, PXN, PAK2, NRAS, RRAS, ACTA2, ITGA2, RAC1, HRAS, ERBB3, ITGA3, PAK1, ARHGEF6, LAMB1, DAG1, ACTG2, AGRN, CTTN Aldosterone Signaling in Epithelial Cells 9.550E-03 ICMT, HSPA1A/HSPA1B, SGK1, PIK3R1, DNAJC12, HSPB8, HSPA6, DNAJC10, DNAJC15, DNAJA1, SLC9A1, PRKCZ, HSPA4, HSP90AB1, PLCB1, DNAJB1, PIK3R2, ATM, HSPA4L, DNAJC9, HSPH1, SLC12A2, HSPA9, DNAJC25, HSPD1, DNAJB9, HSPA2, HSPA8, DNAJC24, PIP5K1C, DUSP1, DNAJB11, HSP90AA1, PRKCH
(a) (ii)
Network Score Molecules in Network Focus Molecules Top Functions
28 ATP6V0E1, BRWD1, C11orf82, C12orf76, CDCA2, CDCA7, CDK4, CENPK, CENPN, CNOT7, DONSON, E2F7, ENDOD1, FAM54A, FAM83D, GPC6, HIST2H2BE 35 Cellular Assembly and Organization, DNA Replication, Recombination, and Repair, Developmental Disorder (includes others), HJURP, HSPD1, KIF20A, KIF2C, MBLAC2, MED30, PDLIM3, PPCS, RNF170, RPS27L, SERF2, SGOL2, SLC29A1, TM7SF2, TMEM219, TMSB15A, TP53INP1, TRIP13 28 CALU, CBX1, CBX6, CCPG1, CREBRF, CRISPLD2, DNMT1, EMC9, ERGIC1, EZH2, FAM46B, GPR68, HIST1H2BJ/HIST1H2BK, HSD17B11, KHSRP, KIFC2, KRT17, 35 Small Molecule Biochemistry, Endocrine System Development and Function, Cellular Development KRT81, LYPD6B, NUDT2, PLK2, RAB35, RALB, RBMS1, RUVBL1, SFR1, SLC25A25, SRD5A1, STX6, SUV39H1, SUZ12, TIPARP, TNS3, TRIM52, VAMP3 25 ACTL6A, AEBP2, Cbp/p300, CDCA3, CDIPT, CENPE, CENPF, CSNK2A2, DNAL4, EED, EIF5B, FJX1, HDAC2, KDM1A, KDM5B, LRCH4, MAPK8IP3, MT1F, NDC80, 34 Cell Cycle, Cellular Assembly and Organization, DNA Replication, Recombination, and Repair NEK2, NEK11, NUF2, OGG1, OIP5, PIR, POLD3, PPOX, RNASET2, SAP30, SMARCC1, SMARCE1, SPC25, TOP2A, TOP2B, UBE2C 23 ADARB1, AK4, AMD1, DKK1, DNAJA1, EDN1, EIF1AX, EPHA1, FKBP4, FKBP5, GJA1, GOT1, Hsp90, IP6K2, Jnk, KCNK1, KLF2, LAMB2, MAD2L2, MAP3K11, 33 Drug Metabolism, Endocrine System Development and Function, Lipid Metabolism MSH2, MSH6, NCOA3, PCNA, PGR, PRMT5, RAB9A, S100P, SERPINB8, SLC31A2, SNTB2, TMED10, UCK2, URI1, ZC3H12A 23 26s Proteasome, ADRM1, BRCA1, CDC6, CDCA4, CEP55, CHEK1, CKS1B, DYNLL1, FBXO5, GMNN, HAUS8, KIF11, LMNB2, MCM3, MCM5, MCM7, MCMBP, 33 DNA Replication, Recombination, and Repair, Cell Cycle, Cellular Assembly and Organization NABP1, NEDD1, NFKBIA, ORC5, ORC6, PABPC1, PLK1, PRMT2, PSMA1, PSMB1, PSMB5, RECQL4, SLC39A4, TAF4B, Ubiquitin, UBQLN1, UBQLN2 23 ADD3, AKAP8, AURKA, AURKB, BAZ1A, CDCA8, CHFR, CRIP2, DHRS12, DIO1, DMAP1, ERMAP, H2AFZ, Histone h3, Histone h4, KIF22, KIF4A, LARP1B, NCAPD2, 33 DNA Replication, Recombination, and Repair, Cellular Assembly and Organization, Cell Cycle NCAPD3, NCAPG, PNO1, POLD4, POLE2, POLE3, RPS9, SF3B3, SMC2, SPATS2L, STOM, TACC3, VRK1, WDR1, ZDHHC11, ZNF239 23 20s proteasome, BAG1, CALB2, CD24, CLDN3, CLDN23, COL9A2, DEPDC1, estrogen receptor, F12, FGF13, FXR1, HSPA4, LPXN, LYN, MMP15, N4BP3, NAGK, 33 Neurological Disease, Cell Morphology, Hematological System Development and Function NCAM2, NR2C1, PAAF1, PCDH19, POMP, PPP1R15A, PSMC1, PSMC2, PSMD1, PSMD2, SAT1, TFAP2C, TGFB3, TMEM135, TPP2, TRAFD1, TUFT1 23 APBB3, CA12, DDX39A, DNAJB11, DNAJC10, ELK4, ENO1, GREB1, HCST, HMGB2, HSF1, HSPA8, HSPA1A/HSPA1B, NBPF15 (includes others), NCOA1, NCOA4, 33 Post-Translational Modification, Protein Folding, Drug Metabolism PDZK1, PKMYT1, POLR2D, POLR2I, RAD51AP1, RNA polymerase II, RPA1, SCAF8, SET, SLC27A2, SLC9A8, SLIRP, SMYD3, SPAG7, TBPL1, TFF1, TFIIA, THOC1, THRA 23 ABCC3, ACTA2, APLP2, CCNDBP1, CEP164, Collagen(s), CRTAP, CTPS1, DAG1, DCP1A, DOCK11, GAPVD1, ITGA3, KIF2A, NPR3, PLEC, PLXDC2, PNPLA2, 33 Cancer, Cell-To-Cell Signaling and Interaction, Cell Morphology PODXL, POMGNT1, PTRF, RAB27B, RAI14, SCARA3, SDC1, SDC2, Secretase gamma, SLC35C2, SLC43A2, SVIL, SYVN1, TFAP2A, TRERF1, USP37, YWHAG 22 ACVR1, AHSA1, AIMP2, AKAP1, BAD, BMPR2, CDC42EP5, CHP1, CLIC4, CTGF, DNAJB1, EEF1E1, EPRS, ERK1/2, FAIM3, GPER, GRB7, GRK6, IARS, ID1, IDE, 32 Metabolic Disease, Cellular Development, Cellular Growth and Proliferation LARS, MARS, NEU1, PARVA, Pka, PPAP2C, QARS, RPL8, SLC9A1, SMAD1/5, SRPK1, STAM, SULF2, VEGFB
(b) (i)
Canonical Pathways p-value Genes Mismatch Repair in Eukaryotes 3.162E-10 MSH3, RFC5, POLD1, PCNA, MSH2, RFC4, MSH6, RFC2, PMS2, SLC19A1, FEN1, EXO1, RFC3 Mitotic Roles of Polo-Like Kinase 4.786E-08 KIF23, SMC3, CDC25C, ESPL1, CDC20, ANAPC1/ANAPC1P1, WEE1, PTTG1, PRC1, CDC7, CCNB2, PLK1, CDK1, CCNB1, PLK4, HSP90AB1, PPM1J, HSP90AA1, PKMYT1, FBXO5, PPP2R5C, PPP2R2C, KIF11, CDC25A Role of CHK Proteins in Cell Cycle Checkpoint Control 8.511E-06 CDC25C, MDC1, PLK1, RFC5, CDK1, CHEK1, PCNA, RFC4, PPM1J, RFC2, SLC19A1, TLK1, PPP2R2C, PPP2R5C, BRCA1, E2F2, CDK2, RFC3, CDC25A Cell Cycle: G2/M DNA Damage Checkpoint Regulation 1.479E-05 PRKDC, CDC25C, CKS2, CDK7, WEE1, CCNB2, PLK1, CDK1, PRKCZ, SKP2, CHEK1, CCNB1, CKS1B, TOP2A, PKMYT1, BRCA1 Cyclins and Cell Cycle Regulation 5.129E-05 HDAC2, TFDP1, SUV39H1, CDK7, WEE1, CDKN2D, CCNB2, CCND1, CDK1, SKP2, CCNB1, CCNA2, MYT1, HDAC11, PPM1J, CDK4, TGFB3, PPP2R5C, PPP2R2C, E2F2, CDK2, CDC25A Hereditary Breast Cancer Signaling 7.586E-05 POLR2D, CCND1, SMARCA4, PTEN, CHEK1, HDAC11, RFC2, POLR2H, PMS2, SLC19A1, BRCA1, BLM, POLR2J2/POLR2J3, CDC25C, NRAS, HDAC2, WEE1, TUBG1, RFC5, CDK1, FANCL, CCNB1, MSH2, RFC4, SMARCA2, CDK4, MSH6, RFC3 RAN Signaling 1.950E-04 KPNB1, RCC1, CSE1L, KPNA2, RANGAP1, RAN, XPO1, RANBP1 Estrogen-mediated S-phase Entry 2.042E-04 CCNA2, TFDP1, CDK4, CCND1, ESR1, CDK1, E2F2, CDK2, SKP2, CDC25A Aryl Hydrocarbon Receptor Signaling 3.090E-04 TRIP11, ALDH4A1, NFIX, GSTM5, HSPB2, CCND1, SMARCA4, CHEK1, NR2F1, CCNA2, GSTM2, ALDH1A1, HSP90AB1, TFF1, RARA, GSTM4, TFDP1, GSTM3, NCOA3, CDK4, TGFB3, HSP90AA1, NFIB, NRIP1, GSTO2, ESR1, CDK2, GSTP1, MCM7, HSPB1 Cell Cycle Control of Chromosomal Replication 6.310E-04 MCM3, RPA3, MCM2, CDT1, CDK4, CDK7, CDC7, ORC6, CDK2, MCM7 GADD45 Signaling 8.318E-04 PCNA, CDK4, MAP3K4, BRCA1, CCND1, CDK1, CDK2, CCNB1 ATM Signaling 1.000E-03 SMC3, CDC25C, MDC1, CCNB2, CDK1, CHEK1, CCNB1, SMC2, CREB1, MAPK10, ATF4, TLK1, BLM, BRCA1, CDK2, CDC25A Role of BRCA1 in DNA Damage Response 1.202E-03 MDC1, PLK1, RFC5, SMARCA4, FANCL, CHEK1, MSH2, RFC4, SMARCA2, MSH6, RFC2, SLC19A1, BRCA1, BLM, E2F2, RFC3 Calcium-induced T Lymphocyte Apoptosis 2.344E-03 HLA-DMA, HLA-DOA, HDAC2, CD4, PLCG1, ATP2A3, HLA-DMB, HLA-DQB1, ITPR1, ATP2A2, PRKCZ, CABIN1, CALM1 (includes others), ITPR3, PRKCH Pyrimidine Deoxyribonucleotides De Novo Biosynthesis I 3.388E-03 TYMS, DUT, NME1, RRM2, DTYMK, RRM1 Purine Nucleotides De Novo Biosynthesis II 5.623E-03 IMPDH2, PAICS, PPAT, ATIC, GART LPS/IL-1 Mediated Inhibition of RXR Function 7.762E-03 APOE, ALDH4A1, GSTM5, SLC27A2, ABCG1, APOC2, CES2, SOD3, CHST15, ABCA1, CETP, IL1R2, SLC27A5, ALDH1A1, GSTM2, CYP3A5, RARA, GSTM4, XPO1, CHST10, FMO1, TNFRSF1B, ACOX2, GSTM3, CYP2A7, IL1R1, APOC1, TLR4, HS3ST2, NCOA1, CPT2, SLC27A1, PLTP, ACOX3, GSTO2, GSTP1, CYP2C8 Aldosterone Signaling in Epithelial Cells 9.772E-03 HSPA14, HSPB2, DNAJC12, HSPB8, DNAJA1, SLC9A1, PRKCZ, SCNN1A, HSPA4, HSPA12B, HSP90AB1, DNAJC22, PLCD4, HSPB6, AHCY, DNAJC9, HSPH1, HSPA9, PLCG1, PLCL2, ITPR1, DNAJB11, ITPR3, HSP90AA1, NR3C2, PRKCH, PIP4K2C, HSPB1
(b) (ii)
Network Score Molecules in Network Focus Molecules Top Functions
32 C11orf82, CALCOCO1, CCND1, CDCA2, CDCA7, CDCA8, CDK4, CENPF, CENPK, CENPN, CEP55, CPED1, DONSON, E2F7, ENDOD1, FAM54A, FAM83D, H2AFJ, HIST2H2BE 35 Cell Cycle, Cellular Assembly and Organization, DNA Replication, Recombination, and Repair (includes others), HJURP, KDELR2, KIAA0101, KIF11, KIF20A, KIF20B, KIF2C, KIF4A, MELK, MTMR1, MYT1, RFC5, STOM, SUGP2, TMSB15A, TRIP13 29 ARHGAP28, BOP1, CALM1 (includes others), CAMK2D, CARD10, CLEC11A, CXCL16, FASTKD5, FBL, FUCA1, GNL2, GNL3, GTPBP4, IL10RA, LDB2, LSP1, METTL1, NFkB 34 RNA Post-Transcriptional Modification, Post-Translational Modification, Protein Folding (complex), NHP2L1, NME1, NOP56, NOP58, NUP62, PPP1R16B, PPP4R4, RLN2, RUSC2, TFG, TNFRSF18, TNIP3, UBA7, UBE2E2, UHMK1, WDR12, WDR34 29 CABIN1, CDC7, CDCA4, CDT1, CENPE, EGR2, FBXW5, GMNN, HSD17B8, IARS2, KDM5B, LRWD1, MAP2K3, MAPKAPK2, MCM2, MCM3, MCM7, NDC80, NDRG2, NEDD4L, 34 Cellular Assembly and Organization, Cell Cycle, DNA Replication, Recombination, and Repair NFYC, NR3C2, NUF2, P38 MAPK, PBK, PHF15, RANBP1, RBP1, RRAD, SAP30, SCNN1A, SPC25, TACC3, TOP2A, TSC22D3 27 ABCC5, C1QTNF6, CD74, CELSR2, CITED1, collagen, COMT, CRABP2, CTSS, DNAJA3, ENO1, ESR1, FAM100A, GPS2, GREB1, HSPA9, ICOSLG, KCNK6, MAP2K1/2, MKI67, 33 Cancer, Organismal Injury and Abnormalities, Cellular Assembly and Organization MKI67IP, PDCD4, PDZK1, PLCD4, RARA, RHOG, SLC26A3, SLC7A5, STC2, TBL1X, TFAP2C, TM4SF1, TMEM97, VAV3, ZNF703 27 AMD1, CAPG, CD68, CDH5, CNNM4, COL3A1, COL6A1, COL6A2, COL6A3, COL9A2, Collagen Alpha1, DCHS1, DSP, estrogen receptor, FBN1, FGFR3, FLNC, FMOD, LTBP3, 33 Hereditary Disorder, Skeletal and Muscular Disorders, Cancer LY6E, MPHOSPH9, MSX2, NFIB, PAQR7, PDPN, PGR, PLEK2, SAT1, SPARC, TGFB3, TGFBR2, TJP3, TWIST1, UCK2, WISP2 25 AMBRA1, AR, CDK2, Cdk, CDKN1C, CHTF18, Cyclin A, Cyclin E, DCTPP1, DSCC1, ELP5, EXO1, FEN1, HIVEP2, HSPH1, LIG1, MSH3, MYO1B, PARPBP, PCNA, PMS2, 32 DNA Replication, Recombination, and Repair, Cancer, Hematological Disease POLD1, PRKDC, PROS1, PSMD5, RFC2, RFC3, RFC4, RFX1, SKP2, SMARCC1, TMPRSS2, TUBB3, WEE1, XPO1 24 ACTL6A, ASF1B, AURKB, BTG3, CBX3, CCRN4L, CDK7, CHAF1A, CHAF1B, DHRS12, DPT, H2AFZ, HDAC2, Hdac, Histone h3, Histone h4, HOXA9, HOXA10, NCAPD2, 31 DNA Replication, Recombination, and Repair, Cellular Assembly and Organization, Cell Cycle NCAPD3, NCAPG, NCOA1, PREX1, RUNX1T1, SEC31A, SLIRP, SMARCA2, SMC2, TAF4, TFF1, THRAP3, thymidine kinase, VRK1, WDHD1, ZNF239 24 ANLN, BLM, BRCA1, CCNB2, CSDE1, CYP11A1, CYP27B1, DEPDC1, E2f, FANCL, FOXO1, GABPB1, GEMIN6, I kappa b kinase, MTHFD1, NUSAP1, OIP5, PGRMC1, PLAGL1, 31 Cell Cycle, DNA Replication, Recombination, and Repair, Nucleic Acid Metabolism PRR11, RAD51C, RMI1, RPA3, RPA, SFPQ, SHMT1, STRA13, STRAP, TFCP2L1, TFDP1, TFIIH, TTK, TYMS, UBE2I, XRCC3 24 ADCY9, ALPL, ARL6IP5, ARPC1A, ATP2A2, BAG1, CASP4, CYFIP2, DAB2, DHRS3, FKBP4, FSH, GNRH1, GOT1, H6PD, HCLS1, Hsp70, Hsp90, HSPA4, ING2, INHBB, Lh, 31 Organ Morphology, Cancer, Gastrointestinal Disease LOC81691, LYPD3, MSMB, PPIH, PPP2R5C, RAB2A, RAB5C, SH3BP4, STS, TERF2IP, TINF2, TK1, TLK1 22 APC (complex), ARHGEF4, ASCL1, AURKA, C8orf44-SGK3/SGK3, Cbp/p300, CCNA2, CCNB1, CDC20, CDC25C, CDK1, CDK5R1, CKAP2, Cyclin B, ESPL1, FBXO5, FOXM1, 30 Cell Cycle, DNA Replication, Recombination, and Repair, Cancer IMPDH2, ITPR1, KIF14, KIF23, LMO3, MAD2L1, MSH2, MSH6, PFKFB3, PI3K (complex), PLK1, PRC1, PTTG1, Ras homolog, SIRPA, TFRC, TNS1, UBE2C
Supplementary Table S8.
(a) (i)
Canonical Pathways p-value Genes Mismatch Repair in Eukaryotes 1.413E-07 RPA1, RFC5, POLD1, MLH1, PCNA, MSH2, RFC4, MSH6, RFC2, SLC19A1, PMS2, FEN1, EXO1, RFC3 Protein Ubiquitination Pathway 3.162E-06 UBE2H, HSPA14, HSPA1A/HSPA1B, USP5, UBE2L3, UBE3B, UBE2D2, UBE2V2, DNAJC15, PSMC5, HSPA4, DNAJC28, PAN2, BAG1, PSMD10, USP10, UCHL5, DNAJC22, PSMC2, BRCA1, NEDD4L, UBE2J1, PSMA6, PSMB5, DNAJC9, UBE4B, USP36, HSPA9, PSME2, PSMC4, DNAJC25, THOP1, PSMD3, SKP2, HSPA8, UBE2G2, PSMD11, PSMB2, RBX1, PSMD12, ANAPC5, PSMA4, PSMB1, HSP90AA1, PSMD1, DNAJB6, TAP2, VHL, USP51, UBE2C, PSMB3, USP14, ANAPC1/ANAPC1P1, PSMD7, CDC20, DNAJC12, USP11, HSPB8, DNAJC10, DNAJA1, TAP1, USP39, USO1, USP3, USP13, HSP90AB1, PSMC6, HSPE1, PSMD14, AMFR, HSPA4L, UCHL3, USP15, PSMD13, HSPH1, PSMA1, HSPD1, USP1, HSPA2, UBE3A, UBE2L6, DNAJC11, DNAJC24, PSME1, PSMC1, USP4, PSMD2, DNAJB11, UBE2E2, USP37, CDC34, PSMC3, USP49 tRNA Charging 7.244E-06 RARS2, IARS2, GARS, CARS2, MARS2, LARS2, DARS2, MARS, QARS, NARS2, EPRS, EARS2, LARS, WARS, TARS2, YARS, FARS2, KARS, AARS2, AARS, VARS, IARS Cell Cycle: G2/M DNA Damage Checkpoint Regulation 2.692E-05 PRKDC, CDC25C, YWHAG, YWHAH, YWHAE, CKS2, CDK7, WEE1, CCNB2, PLK1, CDK1, PRKCZ, CCNB1, CHEK1, SKP2, YWHAQ, MDM4, TOP2B, CDKN1A, CKS1B, TOP2A, PKMYT1, BRCA1 Mitotic Roles of Polo-Like Kinase 6.761E-05 KIF23, CDC20, ANAPC1/ANAPC1P1, PTTG1, CDC7, PPP2R3B, CCNB2, PLK4, HSP90AB1, PLK2, PPP2R2C, RAD21, CDC25A, SMC3, CDC25C, ESPL1, WEE1, PRC1, PLK1, CDK1, CCNB1, PPP2R1A, CAPN1, ANAPC5, FBXO5, PKMYT1, HSP90AA1, PPP2R1B, KIF11 Cell Cycle Control of Chromosomal Replication 8.913E-05 MCM5, CDT1, CDK7, CDC6, CDC7, CDK6, ORC6, RPA1, MCM3, RPA3, MCM2, CDK4, ORC3, ORC5, CDK2, MCM7 Hereditary Breast Cancer Signaling 9.120E-05 POLR2D, GADD45G, PIK3R1, HRAS, MRE11A, MLH1, CHEK1, FANCB, RB1, POLR2C, PIK3C3, HDAC11, XPC, HDAC7, RFC2, SLC19A1, PMS2, PIK3R2, BRCA1, BLM, CDC25C, HDAC4, C17orf70, NRAS, HDAC2, RRAS, WEE1, CREBBP, TUBG1, CDK6, RPA1, RFC5, FANCL, CDK1, CCNB1, POLR2G, PIK3R3, MSH2, RFC4, CDK4, CDKN1A, MSH6, PIK3CB, POLR2I, RFC3 Role of BRCA1 in DNA Damage Response 2.692E-04 ATRIP, MRE11A, RBL1, MLH1, CHEK1, E2F6, RB1, FANCB, RFC2, SLC19A1, BRCA1, BLM, STAT1, E2F2, RBL2, C17orf70, MDC1, PLK1, RPA1, RFC5, FANCL, POU2F1, MSH2, RFC4, CDKN1A, MSH6, RFC3 Dolichyl-diphosphooligosaccharide Biosynthesis 2.951E-04 ALG3, ALG5, DPM1, ALG6, DPAGT1, ALG8, ALG1, DPM2 Role of CHK Proteins in Cell Cycle Checkpoint Control 3.715E-04 PPP2R3B, MRE11A, CHEK1, E2F6, RFC2, SLC19A1, PPP2R2C, BRCA1, E2F2, CDC25A, CDC25C, MDC1, PLK1, RPA1, RFC5, CDK1, RAD1, PCNA, PPP2R1A, RFC4, CDKN1A, ATMIN, PPP2R1B, CDK2, RFC3 Molecular Mechanisms of Cancer 4.365E-04 RAPGEF1, BMP4, APH1B, SUV39H1, PIK3R1, SOS2, HRAS, NCSTN, MAPK13, RBL1, RB1, ZBTB17, NFKBIB, HIPK2, PRKD1, STK36, TFDP1, RRAS, CREBBP, RALB, ARHGEF17, NFKB2, GAB1, IRS1, APH1A, ARHGEF6, MAP2K3, ARHGEF18, CAMK2G, RAP2A, RALA, ARHGEF7, RHOT2, BMPR2, PSEN2, PRKCZ, CHEK1, PIK3C3, BID, PIK3R2, BMP1, CAMK2B, PRKDC, PAK2, RHOC, ADCY6, NAIP, FOS, ARHGEF5, RASGRP1, CDKN1A, GAB2, JAK1, SMAD3, TGFBR2, E2F6, RHOG, CASP9, RHOB, BRCA1, RASA1, FZD2, RALGDS, E2F2, CDC25A, ADCY9, RAC1, CDK6, FZD9, AURKA, RALBP1, PIK3R3, BCL2L1, BMPR1B, RHOQ, RABIF, RND3, ARHGEF16, PRKCD, CDK4, TGFB3, PRKCH, LEF1, FNBP1, CDK2, PA2G4, CDKN2B, MAPK11, BCL2, LAMTOR3, NFKBIA, PRKAR1B, TGFB2, ARHGEF2, SRC, CDC25C, NRAS, ARHGEF12, HAT1, ADCY3, PRKAR2A, APAF1, SMAD6, GNAI2, FOXO1, PIK3CB, ELK1 Tetrahydrofolate Salvage from 5,10-methenyltetrahydrofolate 7.762E-04 MTHFD2, MTHFD1, MTHFD2L, MTHFD1L, GART Interferon Signaling 8.318E-04 IFIT3, OAS1, JAK1, PIAS1, IFNGR2, IRF9, MX1, IFNGR1, IFI35, IFNAR2, TAP1, IRF1, BCL2, IFIT1, IFITM1, STAT2, STAT1 Superpathway of Cholesterol Biosynthesis 1.514E-03 MVD, SQLE, ACAT2, IDI1, HSD17B7, MSMO1, TM7SF2, SC5DL, FDPS, FDFT1, MVK, HMGCR, HMGCS1, CYP51A1 Cleavage and Polyadenylation of Pre-mRNA 2.042E-03 CPSF2, PAPOLA, CPSF6, NUDT21, PABPN1, CPSF1, CSTF2, CSTF3 Cyclins and Cell Cycle Regulation 2.291E-03 PA2G4, SUV39H1, PPP2R3B, CCNB2, CDKN2B, E2F6, RB1, CCNA2, HDAC11, HDAC7, TGFB2, PPP2R2C, E2F2, CDC25A, CCNH, HDAC4, TFDP1, HDAC2, WEE1, CDK7, CDK6, CDK1, CCNB1, SKP2, PPP2R1A, CDK4, CDKN1A, TGFB3, PPP2R1B, CDK2 3-phosphoinositide Biosynthesis 2.951E-03 SOCS3, DUSP8, PPP1R12C, NUDT3, EPHX2, PIK3R1, PPFIBP2, PIP4K2B, NUDT14, IGBP1, NUDT2, SET, DUSP2, SACM1L, PIK3C3, PPP1R13B, PTPN1, PIK3R2, RASA1, RNGTT, PI4KB, CDC25A, PPFIA1, PTPN7, PTPN6, CDC25C, PPP1R8, FIG4, PAWR, PGAM4, NUDT15, PPAPDC2, PIK3R3, NUDT5, TNS3, MTMR4, PDXP, DUSP1, PIP5K1C, CDIPT, ACP1, PPM1H, SSH3, DUSP23, DUSP18, PIK3CB, PIP4K2A, DUSP16 Cell Cycle: G1/S Checkpoint Regulation 3.090E-03 RBL2, HDAC4, PA2G4, TFDP1, HDAC2, SUV39H1, SMAD3, PAK1IP1, CDK6, RBL1, CDKN2B, SKP2, RB1, E2F6, HDAC11, CDK4, CDKN1A, HDAC7, TGFB3, TGFB2, GNL3, E2F2, CDK2, CDC25A Chronic Myeloid Leukemia Signaling 3.388E-03 GAB2, PA2G4, SMAD3, PIK3R1, SUV39H1, SOS2, HRAS, RBL1, TGFBR2, E2F6, RB1, PIK3C3, HDAC11, HDAC7, TGFB2, PIK3R2, CHUK, E2F2, STAT5A, RBL2, HDAC4, NRAS, TFDP1, HDAC2, RRAS, CDK6, NFKB2, MECOM, PIK3R3, BCL2L1, CDK4, CDKN1A, TGFB3, PIK3CB Glucocorticoid Receptor Signaling 3.388E-03 TAF4B, POLR2D, JAK1, YWHAH, HSPA14, PRKAB2, PRKAB1, SGK1, HSPA1A/HSPA1B, SMAD3, PIK3R1, SOS2, HRAS, GTF2E2, TAF10, MAPK13, TSC22D3, PGR, TGFBR2, HSPA4, BAG1, PRKAA1, SERPINE1, NFKBIB, STAT5A, RRAS, MED1, CDK7, CREBBP, HSPA9, RAC1, GTF2F1, STAT3, NCOA3, HSPA8, PIK3R3, BCL2L1, POU2F1, TAF5, DUSP1, ERCC3, TGFB3, NCOA1, HSP90AA1, POLR2I, CCL5, TAF7, MAPK11, BCL2, NFAT5, POLR2C, NFKBIA, PCK2, HSP90AB1, PIK3C3, CREB1, FOXO3, CEBPA, TGFB2, PIK3R2, CHUK, STAT1, FKBP5, TAF2, GTF2H3, CCNH, NRAS, MAP3K1, CHP1, HSPA2, TSG101, POLR2G, FOS, GTF2E1, CDKN1A, FKBP4, PIK3CB, PLAU, NCOR2, NRIP1, ELK1 Breast Cancer Regulation by Stathmin1 3.715E-03 CAMK1D, PIK3R1, SOS2, GNG13, PPP2R3B, HRAS, TUBB, GNB1, GNB4, E2F6, STMN1, E2F2, PRKD1, ADCY9, TUBB3, RRAS, RAC1, ARHGEF17, PPP1R11, TUBA1B, GNG10, PIK3R3, PPP2R1A, PRKCD, ARHGEF16, ARHGEF6, PRKCH, ARHGEF18, TUBA3C/TUBA3D, CDK2, CAMK2G, TUBA3E, PPP1R3C, ARHGEF7, PRKCZ, GNG7, PIK3C3, RB1CC1, PRKAR1B, PPP2R2C, ARHGEF2, PIK3R2, CAMK2B, CALML5, ARHGEF12, NRAS, TUBB4B, TUBG1, ADCY3, ADCY6, PRKAR2A, TSG101, CDK1, GNAI2, ARHGEF5, CALM1 (includes others), PPP1R3D, TUBA1A, TUBB6, CDKN1A, PIK3CB, PPP2R1B p53 Signaling 4.074E-03 JMY, GADD45G, PIK3R1, C12orf5, BCL2, CHEK1, RB1, STAG1, PIK3C3, PPP1R13B, PIK3R2, HIPK2, BRCA1, TNFRSF10A, PRKDC, TP53INP1, TOPBP1, MED1, THBS1, TNFRSF10B, APAF1, CSNK1D, SERPINE2, PIK3R3, BCL2L1, PCNA, MDM4, SNAI2, CDK4, CDKN1A, PIK3CB, GNL3, CDK2, DRAM1 Prostate Cancer Signaling 4.467E-03 PA2G4, SRD5A1, PIK3R1, SUV39H1, SOS2, HRAS, BCL2, RB1, CASP9, NFKBIA, HSP90AB1, PIK3C3, CREB1, PIK3R2, CHUK, NFKBIB, NRAS, TFDP1, RRAS, CREBBP, CREB3L4, NFKB2, PIK3R3, FOXO1, CDKN1A, NKX3-1, HSP90AA1, PIK3CB, LEF1, CDK2 IGF-1 Signaling 4.677E-03 IGFBP4, SOCS3, CTGF, JAK1, YWHAH, PIK3R1, SOS2, SOCS2, HRAS, PRKCZ, YWHAQ, CASP9, PIK3C3, FOXO3, CSNK2A1, PRKAR1B, PIK3R2, RASA1, PXN, YWHAG, NRAS, YWHAE, RRAS, PRKAR2A, IGFBP5, STAT3, PIK3R3, CSNK2A2, FOS, NOV, FOXO1, IRS1, IGFBP3, PIK3CB, ELK1 Estrogen-mediated S-phase Entry 4.898E-03 CCNA2, RB1, E2F6, TFDP1, CDK4, CDKN1A, RBL1, CDK1, E2F2, CDK2, SKP2, CDC25A mTOR Signaling 5.370E-03 PLD2, PRKAB2, PRKAB1, PIK3R1, PPP2R3B, HRAS, EIF4A2, RPS23, RPS7, RHOG, RHOB, EIF4G2, EIF3D, TSC2, PRKAA1, PRKD1, RHEB, PLD3, DDIT4, RRAS, RAC1, VEGFC, PIK3R3, PPP2R1A, RHOQ, RND3, EIF4A3, PRKCD, IRS1, PRKCH, FNBP1, RPS27A, TSC1, ULK1, RHOT2, RPS6KA3, VEGFB, FKBP1A, RPS21, PRKCZ, EIF4EBP1, RPS27, PIK3C3, RPS9, EIF3A, RPTOR, PPP2R2C, PIK3R2, RPS6KA2, NRAS, EIF3H, EIF3F, RHOC, RPS27L, EIF3G, RPS26, PIK3CB, PPP2R1B, EIF3L Small Cell Lung Cancer Signaling 5.370E-03 PA2G4, PIK3R1, SUV39H1, CDKN2B, BCL2, RB1, NFKBIA, CASP9, PIK3C3, BID, CHUK, PIK3R2, RXRB, NFKBIB, TRAF1, TFDP1, APAF1, CDK6, NFKB2, SKP2, PIK3R3, BCL2L1, CDK4, CKS1B, PIK3CB, RXRA, CDK2 Aryl Hydrocarbon Receptor Signaling 5.888E-03 ALDH4A1, NFIX, NQO2, CHEK1, CCNA2, GSTT1, RB1, TFF1, HSP90AB1, ALDH1A3, ALDH3A2, RARA, TGFB2, GSTM4, RXRB, AHR, GSTK1, SRC, ALDH1B1, GSTM1, MGST1, NFIC, TFDP1, MED1, GSTM3, NQO1, APAF1, CDK6, NFKB2, NCOA3, GSTO1, CYP1B1, FOS, ALDH1L2, NFIA, CDK4, CDKN1A, TGFB3, HSP90AA1, NCOR2, NRIP1, ALDH3B2, RXRA, CDK2, MCM7 ATM Signaling 6.918E-03 SMC3, CDC25C, GADD45G, CREBBP, MDC1, CCNB2, MRE11A, CREB3L4, MAPK13, MAPK11, CDK1, CHEK1, CCNB1, MDM4, NFKBIA, SMC2, CREB1, CDKN1A, BID, BLM, BRCA1, CDK2, CDC25A Pyrimidine Deoxyribonucleotides De Novo Biosynthesis I 7.762E-03 TYMS, NME3, DUT, NME1, RRM2, DTYMK, RRM1, NME6 Remodeling of Epithelial Adherens Junctions 7.762E-03 NME1, RALA, TUBA3E, ACTA2, RAB5B, IQGAP1, TUBB, ARPC4, VCL, ACTG2, HGS, DNM2, SRC, TUBB3, TUBB4B, MAPRE1, TUBG1, RAB7A, TUBA1B, TUBA1A, TUBB6, ZYX, TUBA3C/TUBA3D, DNM1L, MAPRE3 ERK5 Signaling 8.318E-03 SRC, YWHAG, NRAS, YWHAH, YWHAE, SGK1, RRAS, CREBBP, RPS6KA3, HRAS, CREB3L4, PRKCZ, CTF1, YWHAQ, FOS, GAB1, MEF2D, CREB1, FOXO3, MAP3K8, RPS6KA2, MAP2K5, ELK4, MAP3K2 3-phosphoinositide Degradation 9.333E-03 SOCS3, DUSP8, PPP1R12C, NUDT3, EPHX2, PPFIBP2, NUDT14, INPPL1, IGBP1, NUDT2, SET, DUSP2, SACM1L, PPP1R13B, PTPN1, RASA1, RNGTT, MTMR3, CDC25A, PPFIA1, PTPN6, CDC25C, PTPN7, INPP5E, PPP1R8, MTMR14, FIG4, PAWR, PGAM4, NUDT15, PPAPDC2, NUDT5, TNS3, MTMR4, INPP5J, PDXP, DUSP1, ACP1, PPM1H, SSH3, DUSP23, DUSP18, DUSP16 JAK/Stat Signaling 9.550E-03 SOCS3, JAK1, PIAS2, PIK3R1, SOCS2, SOS2, PIAS1, HRAS, PIK3C3, PTPN1, PIK3R2, STAT1, STAT6, STAT5A, PTPN6, NRAS, RRAS, STAT3, STAT4, PIK3R3, BCL2L1, FOS, CDKN1A, STAT2, PIK3CB
(a) (ii)
Network Score Molecules in Network Focus Molecules Top Functions 21 ATF6, ATP2A2, ATP5I, BCL9, CREB1, DIO2, EMC9, ERGIC1, FGFR4, FOS, GPER, HIST1H2BH/HIST1H2BO, HIST2H2AC, HYOU1, KIFC2, KPNB1, MARCH6, MECOM, NAE1, 35 Small Molecule Biochemistry, DNA Replication, Recombination, and Repair, Tissue Morphology NBPF15 (includes others), NHP2, NHP2L1, NOP58, NUCKS1, NUDCD2, NUFIP1, PMS2, RPAP3, RPS6KA3, RUVBL1, SFTPD, SLC35G1, SNORD13, SRD5A1, TRAM2 21 ARHGDIB, ARHGEF6, ARHGEF7, BAIAP2, DOCK11, DYRK1B, EFNB3, FIP1L1, GAPVD1, INPP5E, KIF2A, MAP7, MAP2K3, N4BP3, NOXA1, NOXO1, NREP, PARVA, PARVB, 35 Cell Morphology, Cellular Assembly and Organization, Cellular Function and Maintenance PHLDB2, PPFIA1, RAC1, RHOG, SHROOM2, SLC25A3, TBC1D7, TNFRSF10A, TNFRSF10B, TSC1, TSC2, USP37, YWHAE, YWHAG, YWHAH, YWHAQ 21 ATP6V0E1, BRWD1, C11orf82, C12orf76, CDCA2, CDCA7, CDK4, CENPK, CENPN, CNOT7, DONSON, E2F7, EIF5A2, ENDOD1, FAM54A, FAM83D, H2AFJ, HJURP, KIF20B, LIN7B, 35 Developmental Disorder, Reproductive System Disease, Cell Cycle MBLAC2, MED30, MFSD6, PDLIM3, PPCS, RNF170, SERF2, SERINC3, THNSL1, TM7SF2, TMEM219, TOB2, TOR3A, TRAPPC2, TRIP13 19 C4orf27, CIRH1A, CXCL16, DDA1, EGLN3, FASTKD1, FBL, FUCA1, GNL2, GNL3L, GTPBP4, IPO11, LITAF, LUC7L3, MLKL, MUC1, NFkB (complex), NOP14, NQO2, NUP62, 34 Gastrointestinal Disease, Hepatic System Disease, Liver Cirrhosis PDLIM1, RFTN1, RIOK1, RIOK3, RIPK4, ST3GAL1, TAX1BP1, TBC1D4, TFAM, TFG, TRIM8, TRIM69, UBE2E2, UCHL5, WDR34 19 AGK, AP1G2, CDC42EP5, CEP55, CHMP1B, CHMP2A, CHMP4B, CMTM8, ERK1/2, F2RL1, FAIM3, FAM125B, HGS, IDE, LRSAM1, MC1R, MGRN1, NEDD4L, NEU1, P2RY6, 34 Cell Morphology, Infectious Disease, Cellular Assembly and Organization PDCD6, PDCD6IP, PPAP2C, SCRIB, SGSM3, STAM, STAMBP, TNRC6A, TRIM3, TSG101, VPS28, VPS37A, VPS37C, VPS37D, VRK2 19 ADRM1, CD3EAP, CDC34, CKS1B, DNAJA3, DNAJB11, DYNLL1, G3BP2, HIST1H2AC, HSF1, HSPA8, HSPA1A/HSPA1B, LYPLA1, MCM3, MCM5, MCMBP, NFKBIA, NFKBIB, 34 Post-Translational Modification, Protein Folding, Cell Death and Survival PDCD2, POLR1E, PRMT2, PSMA6, RAD1, RPA1, RPA3, RPN1, Scf Trcp beta, SUPT16H, TAF4B, TCERG1, TXNDC17, UBE2D2, UBE3A, UBQLN1, UBQLN2 19 AEBP2, ANXA8L2 (includes others), BPTF, C15orf48, CALU, CCPG1, CRISPLD2, CXCR7, EED, EML4, EZH2, FKBP4, GJA1, HCFC1, HCFC1R1, HSD17B11, Hsp90, IP6K2, 34 Cellular Development, Cellular Growth and Proliferation, Cellular Movement IVNS1ABP, KLF2, MAP3K11, MTA2, NUDT2, PHF19, POLD3, PRICKLE1, RBBP7, RBMS1, SAP30, SFR1, SUZ12, TOP2B, TRIM52, UCHL3, ZBTB33 19 ACTA2, ASNS, CCDC99, CD24, CEBPD, Creb, CYP51A1, GOLGA2, GORASP1, HDAC4, HES1, HSPB8, IRAK1BP1, KLHL22, KNTC1, LAMP2, LGALS1, LPP, LPPR2, MBNL1, 34 Cell Cycle, Digestive System Development and Function, Organismal Development NAGK, NDUFA8, OASL, OGG1, RELB, SPG11, TFPI, THBS1, TMEM135, TPP2, TRAFD1, TRAIP, TUFT1, UROD, USO1 17 ACIN1, ADD3, ASF1B, CBX3, CCRN4L, CHAF1A, CHAF1B, CHMP1A, CRIP2, DHRS12, EFCAB7, ENO3, ERMAP, HIST1H3A (includes others), Histone h3, LARP1B, MAGED2, 33 Cellular Assembly and Organization, DNA Replication, Recombination, and Repair, Gene Expression PALLD, PCBD2, PNO1, POLD4, PRMT6, RPS9, SAP18, Sin3, SPATS2L, STOM, TPM3, USP3, VKORC1, VRK1, WDR1, ZBTB44, ZDHHC11, ZNF239 17 CA12, CDKN3, CSDA, DCTN4, DEPDC1, DHPS, E2F6, ELK4, ERCC8, EXOSC8, FOXM1, GTSE1, HCST, KDM3A, KIF20A, NEK2, NEK11, P-TEFb, PDZK1, PIN1, PKMYT1, PLK4, 33 Cell Cycle, Cellular Development, Cellular Growth and Proliferation PRR15L, RAD51AP1, RNA polymerase II, S100A6, SCAF8, SETD2, SLC27A2, SPAG7, SRSF1, THOC1, TMPO, TPM4, WDR36
(b) (i)
Canonical Pathways p-value Genes Mitotic Roles of Polo-Like Kinase 1.349E-07 KIF23, CDC25C, ESPL1, CDC20, PTTG1, PRC1, PPP2R3B, CCNB2, CDC23, PLK1, CDK1, CCNB1, PLK4, PPM1J, PKMYT1, FBXO5, PPP2R2C, KIF11, RAD21, CDC25A Cyclins and Cell Cycle Regulation 6.166E-06 PA2G4, SUV39H1, PPP2R3B, CCNB2, CCND1, CDK1, SKP2, CCNB1, CCNA2, MYT1, E2F6, CCND2, HDAC11, PPM1J, TGFB3, PPP2R2C, GSK3B, E2F2, CDK2, CDC25A Role of CHK Proteins in Cell Cycle Checkpoint Control 1.096E-05 CDC25C, PPP2R3B, PLK1, RFC5, CDK1, CHEK1, E2F6, PCNA, RFC4, PPM1J, PPP2R2C, BRCA1, E2F2, CDK2, RFC3, CDC25A Mismatch Repair in Eukaryotes 2.138E-05 PCNA, RFC4, MSH3, MSH6, RFC5, POLD1, EXO1, RFC3 Cell Cycle: G2/M DNA Damage Checkpoint Regulation 4.571E-05 PRKDC, CDC25C, CKS2, CCNB2, PLK1, CDK1, SKP2, CHEK1, CCNB1, EP300, TOP2A, PKMYT1, BRCA1 Role of BRCA1 in DNA Damage Response 5.012E-04 ATRIP, PLK1, RFC5, SMARCA4, CHEK1, FANCB, E2F6, FANCD2, RFC4, MSH6, BLM, BRCA1, E2F2, RFC3 Hereditary Breast Cancer Signaling 5.754E-04 CDC25C, UBB, TUBG1, HRAS, RFC5, CCND1, SMARCA4, CDK1, EP300, CHEK1, CCNB1, FANCB, FANCD2, RFC4, HDAC11, MSH6, POLR2H, PIK3R2, BLM, BRCA1, RFC3 Estrogen-mediated S-phase Entry 6.607E-04 CCNA2, E2F6, CCND1, CDK1, E2F2, CDK2, SKP2, CDC25A GADD45 Signaling 7.244E-04 PCNA, CCND2, BRCA1, CCND1, CDK1, CDK2, CCNB1 ATM Signaling 1.380E-03 CDC25C, CCNB2, MAPK11, CDK1, CHEK1, CCNB1, EP300, FANCD2, BRAT1, BLM, BRCA1, CDK2, CDC25A Cell Cycle: G1/S Checkpoint Regulation 1.380E-03 PA2G4, PAK1IP1, SUV39H1, CCND1, SKP2, E2F6, CCND2, HDAC11, TGFB3, GSK3B, E2F2, CDK2, CDC25A Cell Cycle Regulation by BTG Family Proteins 2.399E-03 E2F6, CNOT7, PPM1J, PPP2R3B, PPP2R2C, CCND1, CCRN4L, E2F2, CDK2 Pyrimidine Deoxyribonucleotides De Novo Biosynthesis I 5.012E-03 TYMS, DUT, NME1, DTYMK, RRM1 Tetrahydrofolate Salvage from 5,10-methenyltetrahydrofolate 5.754E-03 MTHFD2, MTHFD2L, GART Pyridoxal 5'-phosphate Salvage Pathway 6.457E-03 DAPK1, FAM20B, NEK2, PDXK, CSNK1D, PRKAA1, PLK1, PRKCH, TTK, CDK1, ACVR2A, CDK2 Regulation of IL-2 Expression in Activated and Anergic T Lymphocytes 6.761E-03 CD247, FYN, NFATC3, HRAS, PPP3CC, NFATC4, MALT1, TGFBR2, CD3G, PLCG2, ZAP70, TGFB3, CHUK, ELK1 Spliceosomal Cycle 7.586E-03 U2AF2, U2AF1 GDP-L-fucose Biosynthesis I (from GDP-D-mannose) 7.586E-03 TSTA3, GMDS Role of NFAT in Regulation of the Immune Response 9.772E-03 CD247, FYN, GNAS, ITPR2, NFATC3, GNA12, GNB2L1, HLA-DQA1, CSNK1D, HRAS, ITPR1, PPP3CC, NFATC4, CD3G, GNG11, PLCG2, GNAO1, ZAP70, PIK3R2, CHUK, GNG2, GSK3B, GNB1L, ITK
(b) (ii)
Network Score Molecules in Network Focus Molecules Top Functions
35 ATP6V0E1, BBX, C11orf82, CCND1, CDCA2, CDCA7, CDCA8, CENPF, CENPK, CENPN, DDX24, DONSON, E2F7, ENPP2, FAM54A, FAM83D, FANCD2, FANCI, FOXM1, H2AFJ, 35 Cell Cycle, Tissue Morphology, Cellular Development HJURP, KIF11, KIF20A, KIF20B, KIF4A, MELK, NCAPD3, NR2C2, PITX2, PRC1, SUGP2, TIGD1, TRIP13, ZBED5, ZFP106 29 AKAP13, ARHGAP28, BAG4, CHUK, CIRH1A, CLEC11A, DDA1, ERAP2, FAF1, FUCA1, GNL2, GNL3L, GTPBP4, HRAS, Ikb, KSR2, LITAF, MLKL, NFkB (complex), NGFRAP1, 32 Cellular Movement, Hematological System Development and Function, Immune Cell Trafficking NOP14, PELI1, PIAS4, Pkc(s), RNMTL1, SLAMF1, ST3GAL1, STAP2, TFAM, TK1, TMEM14C, TRAF3IP2, UBE2E2, WDR34, ZFAND6 29 AFAP1L2, ALDH1A1, Alpha catenin, AXIN1, CTNNB1, CTPS1, DIXDC1, DPAGT1, ECM1, ESPL1, GSK3B, ID3, IQSEC1, KIF23, LBH, MME, MSX1, MYB, NAA10, POSTN, PTTG1, 32 Cancer, Cellular Development, Cell Cycle QPCT, RAB25, RAD23A, SERPINA3, SERPINA5, SLC1A5, SNAI2, SPARC, TCF, TSC22D1, TWIST2, VIM, WISP2, Wnt 29 ADD3, ASF1B, ATAD5, AURKB, BLM, CBX3, CCRN4L, CDC25C, CHAF1A, CHAF1B, CHMP1A, DHRS12, DNMT1, DSN1, H2AFZ, Histone h3, Histone h4, HOXA9, MSH6, MUTYH, 32 Cellular Assembly and Organization, DNA Replication, Recombination, and Repair, Gene Expression MYT1, NFATC2IP, PARPBP, PCNA, RAD21, SEC31A, SF3B3, SPATS2L, SUV39H1, SUV39H2, THRAP3, thymidine kinase, TM4SF18, TPM3, UBB 29 AGR2, ATP2A2, CCPG1, CDC14B, CDC25A, CEP55, CEP70, CHEK1, DAZAP2, E2F2, E2F6, Gamma tubulin, HAUS8, HSD17B11, IL18R1, Interferon alpha, IQCD, KIF2C, LGMN, 32 Cell Cycle, DNA Replication, Recombination, and Repair, Cellular Assembly and Organization PA2G4, PHF19, PLK1, PRKDC, RAD51AP1, Rb, RBMS1, RPL15, SGOL2, SLC7A5, SRP9, SRSF1, SUZ12, TNS3, TRAM2, TYMS 27 Caspase 3/7, CDK1, CDT1, CENPE, CNKSR1, CNOT7, CSRP2, Cyclin B, DCLRE1A, DLGAP5, GSTP1, ITPR1, Jnk, KRT8, LMNB2, LRWD1, MAD2L1, MCM2, MCM3, MCM5, MCM7, 31 Cell Cycle, Cellular Assembly and Organization, DNA Replication, Recombination, and Repair NDC80, NEK2, NUF2, PIAS1, PYHIN1, Ras homolog, RECQL4, RGCC, SIAH2, SPC25, TACC3, TMPRSS2, TNFSF10, TUBG1 27 Actin, ASNS, CAP1, EMP3, ENPP1, GAPDH, GAS8, HEXA, HEXB, KHSRP, KIR2DL3 (includes others), LARS, MN1, MRC2, MREG, MTHFD2, MTORC1, PLD1, PREX1, PVR, Rac, 31 Lipid Metabolism, Small Molecule Biochemistry, Developmental Disorder Rnr, ROR1, RPS6, RPS12, RPS16, RPS19, RPS27, RPS29, RPS4X, SEPP1, SMARCA4, STC2, TRIB3, UBE2L6 25 ABCB1, ABCC4, C8orf44-SGK3/SGK3, CCNT1, CCT3, CCT5, CDK2, Cyclin A, Cyclin E, EHMT2, EMC9, EP300, EWSR1, GCN1L1, GREB1, HIF1AN, Histone H1, KDM4B, KIFC2, 30 Cancer, Drug Metabolism, Lipid Metabolism mediator, NCAPD2, NCAPG, NOP58, NUCKS1, PELP1, PI3K (complex), PLAC8, PPP2R2C, QKI, RUVBL1, SKP2, SMPD1, TGOLN2, TNPO1, UGCG 25 26s Proteasome, Alpha tubulin, ATP13A2, BCAR3, C1QTNF5, CDCA5, COL15A1, Collagen type II, CTSB, CTSK, CTSS, DAPK1, ELK1, ENO3, ERK, FNTA, FUBP1, GPNMB, HBP1, 30 Neurological Disease, Cancer, Cardiovascular System Development and Function IER3, KIAA1524, KIF22, Lfa-1, LRP4, LUM, PAK4, PAXIP1, PLCG2, PPME1, PUF60, SAT1, SNCA, STMN1, TUBA1B, TUBB4B 25 ATRIP, BRAT1, BRCA1, CCNB2, CHTOP, DDX39A, DHX9, FANCB, HLA-E, HOXA5, I kappa b kinase, KAT2A, KLF13, LMO4, MBIP, NCBP1, NCOA1, PARN, PARP, PGR, PRRX1, 30 Cell Cycle, Cellular Assembly and Organization, Cellular Function and Maintenance RAD51C, RMI1, RNA polymerase II, RPA, SAFB, SARNP, SNRPB, SNTB2, Tap, TAPBP, TFF1, TGFB3, UCK2, XRCC3