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