Supplementary Figure 1A HNF4A WNT5A VANGL1 PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1. (B) The expression pattern of the four genes (HNF4A, VANGL1, WNT5A, PLCB1) in various datasets (166 datasets) reported by ArrayExpress. We extracted the expressions of the four genes from ArrayExpress and generated the heatmap by using matrix2png program.
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Supplementary Figure 1A HNF4AWNT5AVANGL1PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1.
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Supplementary Figure 1A
HNF4AWNT5AVANGL1PCLB1
Supplementary Figure 1B
Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1. (B) The expression pattern of the four genes (HNF4A, VANGL1, WNT5A, PLCB1) in various datasets (166 datasets) reported by ArrayExpress. We extracted the expressions of the four genes from ArrayExpress and generated the heatmap by using matrix2png program.
Supplementary Figure 2
Supplementary Figure 2. Example of the selection step of PATHOME. (A) Assumed subpathway toy that consists of 6 nodes and 5 edges. According to our index notation, p is 6 and i 1 to 5. Blunt-ended edge indicates inhibition and arrow-headed edge activation. In each group, nominal values of rk
i,i+1s were given by the table for the following explanation. (B) Following our notation, edges (ei,i+1s) were coded by -1, +1, -1, +1, and +1, from left to right, respectively. Subsequently, we showed how the curly bracket (say yk; k: group index) of the lk (the length of the segment) equation was calculated. The graphs of yk (k=1,2) versus m (1 to 5) indicate that arguments minimizing yks are 4 and 5 for group 1 and group 2, respectively. Thus, l1 and l2 are 5 and 6, respectively. l1 and l2 are considered in the test step of PATHOME.
Supplementary Figure 3
Supplementary Figure 3. Measurement of expression level by RT-PCR, WNT5A, VANGL1, FZD1 and PLCB1, in the gastric cancer cell line panels.
KEGG identifier Description Entries in the significant subpathways belonging to the pathwayhsa04930 Type II diabetes mellitus PIK3R5,PIK3R3,IRS2,PIK3CB,SLC2A4,MAPK1hsa05218 Melanoma IGF1,PDGFC,RAF1,CCND1,NRAS,FGF7,MAPK3,FGF11,MAP2K2,FGF13,FGF2,EGFR,PDGFRB
hsa05213 Endometrial cancer PDPK1,EGF,PIK3CB,CASP9,AKT2,EGFRhsa04114 Oocyte meiosis ITPR3,CDC16,PPP3CB,CCNB1,CALML6,CALML5,PPP3CC,ANAPC4,ITPR1,ANAPC5hsa04666 Fc gamma R-mediated
hsa05120 Epithelial cell signaling in Helicobacter pylori infection
NFKB1,NFKBIA,IKBKB,CCL5
hsa05142 Chagas disease JUN,MAPK12,IRAK4,TLR9,MAP2K4,MAPK10,FOS,TRAF6,MYD88hsa05215 Prostate cancer IGF1,PDGFC,INSRR,PIK3R2,PIK3CA,AKT2,EGFR,PDGFB,PDGFRB,PIK3R3,PDGFA,EGF,IGF1R,
PIK3CB,CASP9,PDGFRA,TGFA,PIK3R5,PDPK1,PDGFD,FGFR1,AKT3,ERBB2,INS,FOXO1hsa05200 Pathways in cancer PGF,NFKB2,VEGFA,CDK4,NFKBIA,BRAF,MAP2K1,EGFR,MMP1,STAT1,BIRC3,IKBKB,EGF,JA
Supplementary Table 1. The 27 KEGG pathways containing the significant 113,810 subpathways in GSE13861 (FDR < 0.05). For the comparison, all the significant subpathways were assigned to their pathways.
KEGG identifer:descrption
P-Value Genes Fold Enrichment
Benjamini FDR (%)
hsa00980:Metabolism of xenobiotics by cytochrome P450
hsa00280:Valine, leucine and isoleucine degradation
0.02914714
BCKDHA, DBT, ALDH6A1, BCAT2, HMGCS2, HADH, ACAT1
2.941735537 0.267710798 29.98156893
Supplementary Table 2. The significant KEGG pathways reported by DAVID in GSE13861. The input genes in DAVID were selected with fold-change 2. The significance cutoff was Benjamini false discovery rate (column Benjamini) < 0.3. The column description refers to the DAVID webpage (david.abcc.ncifcrf.gov).
Supplementary Table 3. The significant KEGG pathways reported by GSEA in GSE13861. The significance was set to FDR q-value < 0.3. The column description refers to GSEA webpage (www.broadinstitute.org/gsea/).
KEGG identifier Description Entries in the significant subpathways belonging to the pathway
hsa04810 Regulation of actin cytoskeleton FGFR2,HRAS,PIK3CB,SOS2
Supplementary Table 4. The 15 KEGG pathways containing the significant 126,095 subpathways in GSE15081. The significance of a supathway was set to FDR-q value < 0.05. For the comparison, all the significant subpathways were assigned to their pathways.
Supplementary Table 5. The significant KEGG pathways reported by DAVID in GSE15081. The input genes in DAVID were selected with fold-change 1.25. The significance cutoff was Benjamini false discovery rate (column Benjamini) < 0.3. The column description refers to the DAVID webpage (david.abcc.ncifcrf.gov/).
Supplementary Table 6. The significant KEGG pathways reported by GSEA in GSE15081. The significance was set to FDR q-value < 0.3. The column description refers to GSEA webpage (www.broadinstitute.org/gsea/).
Supplementary Table 7. The 62 genes belonging to the combined significant subpathways in the discovery stage.
Supplementary Table 8. The expression concordance among the four datasets (GSE13861, GSE36968, GSE15081, GSE27342) in terms of the 62 genes of the combined subpathways in the discovery stage. The similarity was measured by Fisher’s exact test.
Dataset GSE36968 GSE15081 GSE27342
Dataset Group Up1 Down1 Total Up2 Down2 Total Up1 Down1 Total
GSE13861
Up1 22 8 30 22 15 37 14 5 19
Down1 6 13 19 10 12 22 5 11 16
Total 28 21 49 32 27 59 19 16 35
P-value 0.007136 0.4182 0.01849
1Up/Down regulated genes in GC cells over normal-appearing cells.2Up/Down regulated genes in GC peritoneal relapse over non-relapse.