Cofunctional Subpathways Were Regulated by Transcription Factor with Common Motif, Common Family, or Common Tissue

Figure 1

Schematic of the construction of the global TSN based on TF target genes and pathway structure data from KEGG. (a) We extracted 21038 TFs that were verified through biology experiment from Transfac Professional database and then filtered redundant terms and species and obtained 4598 pairs of human TF target gene associations. (b) We used the -clique subpathway method to identify significantly enriched subpathways to generate TF-subpathway associations. (c) We combined these TF-subpathway associations to form the TSN. (d) We used one-way clustering between TFs and subpathways to analyze the regulatory effects of common-motif, common-family, and common-tissue TFs on cofunctional subpathways. (e) Jaccard coefficient was applied to evaluate the functional consistency of the common-motif, common-family, and common-tissue TFs at the subpathway, pathway, and pathway class levels. (f) HNF4A and NR1I3 were a pair of TFs with common motif, common family, and common tissue. Jaccard coefficient at subpathways level, pathways level, and pathway classes level. (g) HNF4A regulated subpathway 00982-10, and NR1I3 regulated subpathway 00982-4, and they have shared genes (CYP3A4, CYP3A5, and CYP2C).