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



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Hindawi Publishing Corporation


Dissecting the characteristics of the transcription factor (TF) regulatory subpathway is helpful for understanding the TF underlying regulatory function in complex biological systems. To gain insight into the influence of TFs on their regulatory subpathways, we constructed a global TF-subpathways network (TSN) to analyze systematically the regulatory effect of common-motif, common-family, or common-tissue TFs on subpathways. We performed cluster analysis to show that the common-motif, common-family, or common-tissue TFs that regulated the same pathway classes tended to cluster together and contribute to the same biological function that led to disease initiation and progression. We analyzed the Jaccard coefficient to show that the functional consistency of subpathways regulated by the TF pairs with common motif, common family, or common tissue was significantly greater than the random TF pairs at the subpathway level, pathway level, and pathway class level. For example, HNF4A (hepatocyte nuclear factor 4, alpha) and NR1I3 (nuclear receptor subfamily 1, group I, member 3) were a pair of TFs with common motif, common family, and common tissue. They were involved in drug metabolism pathways and were liver-specific factors required for physiological transcription. In short, we inferred that the cofunctional subpathways were regulated by common-motif, common-family, or common-tissue TFs.



Jaccard index, Steroid hormones--receptors, Transcription factors, Biological systems, Genes

This work was supported by the National High Technology Research and Development Program of China (863 Program, Grant no. 2014AA02110), the National Program on Key Basic Research Project (973 Program, Grant no. 2014CB910504), the National Natural Science Foundation of China (Grants nos. 91439117 and 61473106), and the Research Project of Health Department of Heilongjiang Province (2014-418).


CC BY 3.0 (Attribution) License, ©2015 The Authors