title: Cofunctional Subpathways Were Regulated by Transcription Factor with Common Motif, Common Family, or Common Tissue.
abstract: 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.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Su
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Desi
authors.initials: D
authors.lastname: Shang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Haixiu
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin 150081, China.
authors.forename: Baoquan
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Computer Science, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA.
authors.forename: Shengyang
authors.initials: S
authors.lastname: Su
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D020816:Amino Acid Motifs; D000090702:Constitutive Androstane Receptor; D005786:Gene Expression Regulation / Q000502:physiology*; D051557:Hepatocyte Nuclear Factor 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009928:Organ Specificity / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000090702:Constitutive Androstane Receptor; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; C000716327:NR1I3 protein, human; D018160:Receptors, Cytoplasmic and Nuclear