title: Critical controllability in proteome-wide protein interaction network integrating transcriptome.
abstract: Recently, the number of essential gene entries has considerably increased. However, little is known about the relationships between essential genes and their functional roles in critical network control at both the structural (protein interaction network) and dynamic (transcriptional) levels, in part because the large size of the network prevents extensive computational analysis. Here, we present an algorithm that identifies the critical control set of nodes by reducing the computational time by 180 times and by expanding the computable network size up to 25 times, from 1,000 to 25,000 nodes. The developed algorithm allows a critical controllability analysis of large integrated systems composed of a transcriptome- and proteome-wide protein interaction network for the first time. The data-driven analysis captures a direct triad association of the structural controllability of genes, lethality and dynamic synchronization of co-expression. We believe that the identified optimized critical network control subsets may be of interest as drug targets; thus, they may be useful for drug design and development.
authors.affiliation: Department of Information Science, Faculty of Science, Toho University, Funabashi, 274-8510, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishitsuka
authors.affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji 611-0011, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Akutsu
authors.affiliation: Department of Information Science, Faculty of Science, Toho University, Funabashi, 274-8510, Japan.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Nacher
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D053263:Gene Regulatory Networks; D020043:Genes, Essential; D060066:Protein Interaction Maps; D020543:Proteome / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D020543:Proteome