Supplement 4

Supplementary Table S4.1. The number of genes and the top molecular and cellular functions associated with genes differentially methylated in response to GGH modulation in HCT116 and MDA-MB-435 cells

Cell Line / GGH Modulation / No. of Genes / Top Function
Hypermethylation
HCT116 / Overexpression / 546 / Cell morphology, cellular development, antigen presentation, cell-to-cell signaling and interaction, cell death
Inhibition / 998 / Cell-to-cell signaling and interaction, amino acid metabolism, drug metabolism, molecular transport, small molecule biochemistry
MDA-MB-435 / Overexpression / 1058 / Cell-to-cell signaling and interaction, cellular movement, lipid metabolism, molecular transport, small molecule biochemistry
Inhibition / 1122 / Cellular movement, cell-to-cell signaling and interaction, cell morphology, cell death, lipid metabolism
Hypomethylation
HCT116 / Overexpression / 359 / Molecular transport, cellular assembly and organization, cell-to-cell signaling and interaction, cellular growth and proliferation, antigen presentation
Inhibition / 871 / Lipid metabolism, molecular transport, small molecule biochemistry, cellular movement, carbohydrate metabolism
MDA-MB-435 / Overexpression / 1336 / Cell-to-cell signaling and interaction, cellular growth and proliferation, cellular movement, cell signaling, molecular transport
Inhibition / 1544 / Cell signaling, molecular transport, vitamin and mineral metabolism, nucleic acid metabolism, small molecule biochemistry

Supplementary Table S4.2. The top networks matched by the genes differentially methylated in both the GGH-modulated HCT116 and MDA-MB-435 cells

GGH Overexpression / GGH Inhibition
No / Top Functions / Score / Focus Genes / Top Functions / Score / Focus Genes
Hypermethylated
1 / Cell Cycle, Cellular Movement, Hematological System Development and Function / 23 / Akt, ALDH1A3, APOC2, CCL13, CCL3L1/CCL3L3, CCND1, CD44 (includes EG:100330801), COL4A2 (includes EG:12827), EGFR, FUCA1, HSPA1L, IL1B, JKAMP, KCNA5, LILRA5, LIN7B, LITAF, MMP9, NFkB (complex), PLA2G3, PLAC1, PLCL1, POPDC2, PPP1R1B, PPT1, PRKAR2B, PTPRS, SCP2, SEMA3C, SERPINB5, TFAM, TNF, TP53 (includes EG:22059), TUB, UBE2V1 / Cell-To-Cell Signaling and Interaction, Hematopoiesis, Cellular Function and Maintenance / 46 / Akt, CALCA, CD4, CHFR, DLX5, DUSP2, ERK1/2, FGF7, FSH, FXN, GNPDA1, H19, Histone h3, IGFBP3, MED21, MGMT, NFkB (complex), NLRP2, NLRP3, NOS3, P38 MAPK, PLAC1, PTGS1, RNA polymerase II, SDC4, SHC3, SLC27A2, SPTA1, SULF2, SYK, TCR, TWIST1, USPL1, VAV1, WT1
2 / Cellular Movement, Immune Cell Trafficking, Inflammatory Response / 7 / AKAP13, BGN, BMX, CCL21, CEACAM8, CYSLTR2, DEK,ERK1/2, HTR4, HTR7, IL8, IL20, IL1RL1, IRAK2, KCNQ1, MAP3K10, MGMT, NKRF, NOD1, OTUD7B, P2RY2, P2RY6, PGF, PTAFR, RELA, Rsk, SENP5, SENP6, SENP7, TMEM9B, TNFSF8, TRAF6, TRPM2, UNC119, VEGFB / Dermatological Diseases and Conditions, Connective Tissue Disorders, Infectious Disease / 14 / ALAS2, ALOX15B, ALOX5AP, BGN, CBS, CCL2, CEBPA, COL18A1, CYP51A1, CYP7B1, EPHB1, F11, HAS2-AS1, HLTF, HNF4A, HSD11B2, IL5RA, INSR, ITGAD, JAK2, KCNMB1, KRT16, KRT81, MAOB, MAT2B, PADI1, PAK7, SERPINB4, SLC19A1, SLC39A8, SP1, SP3, STAT1, TXNRD1, UGT1A9 (includes others)
3 / Cancer, Hematological Disease, Endocrine System Disorders / 2 / ATP10A, TMEM30A / Cell-mediated Immune Response, Cellular Movement, Hematological System Development and Function / 12 / ALDH1A3, BCL6, BPI, CCRL2, CD40, CEACAM3, CXCL16, CYP27A1, FCGR1B, FDCSP, FOXL2, HSP, HSPB3, HSPG2, ICAM1, IFNG (includes EG:15978), IgG, IL17RB, KCNQ1, KLK1 (includes EG:24523), KRT15, MAFF, MAGEA3/MAGEA6, MARCKSL1, PLA2G5, PTGDR, Sod, STAB1, TCEB3B, TNF, TRAF6, TSHR, TYMP, U1 snRNP, VIPR1
4 / Carbohydrate Metabolism, Cell Death, Cellular Assembly and Organization / 2 / MSRB2, PARP1 / Connective Tissue Disorders, Developmental Disorder, Hereditary Disorder / 2 / CCNA2, OFD1
5 / Cell Death, Cellular Development, Connective Tissue Disorders / 2 / ITGBL1, TFAP2A / Cancer, Hematological Disease, Endocrine System Disorders / 2 / ATP10A, TMEM30A
Hypomethylated
1 / Cell Death, Inflammatory Response, Respiratory Disease / 21 / ATG5 (includes EG:11793), CARD8, CARD9, CASP1, EDARADD, ERAP2, GPX4, GRAP2, IGBP1, KCNQ1, KLK10, MGMT, MX2, NFkB (complex), NLRC4, NLRP3, PASK, PVR, RELA, RNF11, SENP6, SHC3, SLC2A5, SLC52A1, SRC, TCR, TLR10, TNFRSF4, TPMT, TRAF6, TRIM38, UBA7, USP20, VHL, WDR3411 / Cellular Movement, Hematological System Development and Function, Immune Cell Trafficking / 39 / ABLIM, AHSP, AKT3, Akt, CCL2, CD1D, CDKN1C, CHFR, CSF3, CXCR4, ERK, ERK1/2, FSH, HAVCR2, Histone h3, Histone h4, HPSE, IGF2, IL12 (complex), ITGB4, ITK, Lh, LOC81691, MAPK6, MYEF2, NFkB (complex), P38 MAPK, RELB, SCARB1, SRD5A2, SULF1, TAB3, TCR, TNFSF12, TRIM69
2 / Lipid Metabolism, Small Molecule Biochemistry, Reproductive System Disease / 21 / ABCG5, AQP3, CDKN1C, Cg, CITED1, CREBL2, CYP11A1, DDC, FSH, G6PC, GATA4, GCG, GCKR, GNRHR, GOT1, GPR101, GPRC5A, HBP1, HNF1A, HSD3B1, INS, ITM2A, JDP2, MT1X, NR0B1, PCK1 (includes EG:18534), PGR (includes EG:18667), PTGS2, PTP4A1, RAB33B, RASSF2, SLC31A2, TM4SF4, WT1, ZNF217 / Cell Morphology, Cancer, Hematological Disease / 15 / ACSL3, AIP, AK1, AMOTL2, BIK, BIN1, BIRC5, CHGA, COL18A1, CSNK1D, CYCS, DCTN1, DCTN2, DDIT4, DUOXA1, EPHB1, KCNQ1, LDHA, mir-320, miR-19b-3p (and other miRNAs w/seed GUGCAAA), miR-215 (and other miRNAs w/seed UGACCUA), miR-22-3p (and other miRNAs w/seed AGCUGCC), MLH1, MTHFD2, Pka, PNPLA2, PRKAA, PRODH, SLC16A1, SLC5A8, SYVN1, TNS4, TP53 (includes EG:22059), TP53AIP1, TXN2
3 / Cellular Movement, Infectious Disease, Cellular Development / 2 / EZH2, GPR68 / Metabolic Disease, Cardiovascular Disease, Tissue Morphology / 15 / ABCG5, ABCG8, ACO2 (includes EG:11429), AGR2, CCR1, CYP8B1, CYSLTR2, EVX1, GATA4, GJA5, Hla-Drb, HNF4A, IFNG (includes EG:15978), IL1B, JUN, KIR2DL3 (includes others), MC3R, MEFV, MMP11, MXD1, MYC, MYCBP2, MYOCD, MZF1, NMNAT2, NPC1L1 (includes EG:100329429), PCSK1, PCSK2, PERP, PLA2G5, PRKCA, PVR, SMARCA4, Sod,ZNF217
4 / Cell-To-Cell Signaling and Interaction, Cellular Assembly and Organization, Cellular Function and Maintenance / 2 / AGTR1, BSN / Developmental Disorder, Cell Death, Cell Morphology / 13 / ABCG2, ACAN, ADAMTS4, AFF4, ATF2, CRABP2, CYP24A1, DAB2IP, DCLK1, DUSP10, EFNA1, Erm, ESR1, GNA12, GNAO1, HDAC1, HEXIM1, Hsp70, MMD, MNAT1, Mta, MTNR1A, NID1, PP1-C, PTGFRN, RETN, RXRA, SNAI1, Sod, TH, TM4SF1, TNF, TNPO1, TNPO2, TSHZ3
5 / Cell Cycle, Cancer, Hematological Disease / 2 / MYOM2 (includes EG:17930), PRDM5

The Score indicates the likelihood of the Focus Genes in a network being found together due to random chance; Bold indicates the Focus Genes, the uploaded genes of interest for which information is available in the Ingenuity Knowledge Base.