Table 3.

Classes of L-methionine-responsive gene signatures and their top functions

ID	Molecules in network	Score	Focus	Top functions
1	↓AURKA, ↓AURKB, ↓BIRC5, ↓BUB1, ↓CCNA2, ↓CCNB1, ↓CCNB2, ↓CDC2, ↓CDC20, ↓CDC25C, ↓CDCA8, ↓CENPA, Cyclin B, Cyclin E, E2f, ↓E2F2, ERK, ↓FBXO5, ↓FOXM1, ↓HMMR, ↓KIF14, ↓KIF23, ↓KIF4A, ↓KIFC1, ↑LAMA3, ↓MAD2L1, ↓NDC80, ↓PBK, ↓PRC1, ↓PRR11, ↓RACGAP1, ↓SPC25, ↓TK1, ↓TPX2, ↓TTK	74	31	Cancer, cell cycle, reproductive system disease
2	Alcohol group acceptor phosphotransferase, ↓ASPM, ↓AURKB, ↓BUB1, BUB1B, ↓CCNB2, CCNG1, CDKN2A, ↓CENPE, ↓CEP55, DSN1, E4F1, ↓FEN1, Glutathione peroxidase, ↑GPX8, ↓HJURP, ↓HMGB2, ↓MELK, NCAPD2, NCAPD3, ↓NCAPG2, NCAPH2, ↓NDC80, ↓NEK2, ↓NUSAP1, ↓PRC1, PRIM1, ↓RACGAP1, ↓TACC3, TGFB1, ↓TK1, TP53, ↓TTK, UBE2A, ↓ZWINT (includes EG:11130)	41	21	Cell cycle, cellular assembly and organization, DNA replication, recombination, and repair
3	Ap1, ↓ASF1B, ↑C8ORF4, Caspase, ↓CDC45L, Ck2, ↓CTSL2, Cyclin A, ↓FEN1, ↓GMNN, hCG, Histone h3, Histone h4, ↓KIAA0101, Lamin b, ↓LMNB1, ↓LMNB2, MAP2K1/2, ↓MCM2, ↓MCM3, ↓MCM7, ↓MCM10, ↑NQO1, P38 MAPK, ↓PCNA, Pka, Pkc(s), Rb, RNA polymerase II, RPA, ↓STMN1, ↓TIMELESS, ↓TOP2A, ↓UHRF1, ↓UNG	41	20	DNA replication, recombination, and repair, cancer, gastrointestinal disease
4	ADAM15, ↑ATF3, ↓BUB1, BYSL, CALCR, ↓CCNB2, ↓CDC20, ↓CDC45L, ↓CDKN3, ↓CNTNAP2, CTR9, EGFR, HMGA2, IL6, ↓KIF11, ↓KIF2C, KRT18, LCK, MAD2L2, MPDZ, ↓NMU, ↓NUDT1, ↓OIP5, PDGF BB, ↓POLE2, ↓PSRC1, PTPRK, SELENBP1, ↑SH3BGRL, Tgf beta, ↓TK1, ↓TRIP13, TRO, ↓TROAP	35	18	Cancer, gastrointestinal disease, cell cycle
5	↑AFF3, AGA, ↓AIF1L, ↑AKR1C2, C11ORF48, C15ORF15, C4ORF43, CASP3, ↓CDC45L, ↓CDCA3, ↓CDCA5, ↓CDCA7, DDX27, DFFB, ↓DLGAP5, EIF2S1, ↓GGH, HBXIP, HNF4A, INCENP, IRS1, ↓KIF20A, ↓LMNB1, ↓LYAR, MIRN210 (includes EG:406992), ↓MND1, MYC, NAT10, Proteasome, PWP1, RAD51, ↑RBM4B, TRAF2, ↑VAMP5, ↓WDR51A	30	16	Cancer, gastrointestinal disease, genetic disorder
6	↓FBXO38, KLF7	2	1	Cell death, neurological disease, nervous system development and function

The genes were classified based on molecular networks (www.Ingenuity.com; see text). The downward arrows indicate genes that were down-regulated by L-methionine exposure in both LNCaP and MCF-7 cells, and the upward arrows indicate genes that were up-regulated in both cell lines. The expression of genes indicated without arrows and not in bold-face in these networks was unchanged in response to L-methionine treatment; the expression of four of these genes was changed in only one of the two cell lines (NCAPD3, UBE2A, ADAM15, and C4ORF43). Ingenuity Pathways Analysis computes a score for each network according to the fit of that network to the user-defined set of Focus Genes. This score is derived from a P-value and indicates the likelihood of the Focus Genes in a particular network being found together due to random chance. A score of 2 indicates that there is a 1 in 100 chance that the Focus Genes are together in a network due to random chance. Therefore, scores of 2 or higher have at least a 99% confidence of not being generated by random chance alone. This score is given in the third column of this table, and the number of focus genes that were changed in expression is given in the fourth column