title: Determining Associations between Human Diseases and non-coding RNAs with Critical Roles in Network Control.
abstract: Deciphering the association between life molecules and human diseases is currently an important task in systems biology. Research over the past decade has unveiled that the human genome is almost entirely transcribed, producing a vast number of non-protein-coding RNAs (ncRNAs) with potential regulatory functions. More recent findings suggest that many diseases may not be exclusively linked to mutations in protein-coding genes. The combination of these arguments poses the question of whether ncRNAs that play a critical role in network control are also enriched with disease-associated ncRNAs. To address this question, we mapped the available annotated information of more than 350 human disorders to the largest collection of human ncRNA-protein interactions, which define a bipartite network of almost 93,000 interactions. Using a novel algorithmic-based controllability framework applied to the constructed bipartite network, we found that ncRNAs engaged in critical network control are also statistically linked to human disorders (P-value of P = 9.8 × 10(-109)). Taken together, these findings suggest that the addition of those genes that encode optimized subsets of ncRNAs engaged in critical control within the pool of candidate genes could aid disease gene prioritization studies.
authors.affiliation: Department of Information Science, Faculty of Science, Toho University, Funabashi, 274-8510, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Kagami
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 Intelligence Science and Technology, Graduate School of Informatics, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Maegawa
authors.affiliation: Department of Intelligence Science and Technology, Graduate School of Informatics, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosokawa
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: D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D022661:RNA, Untranslated / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D022661:RNA, Untranslated; D016601:RNA-Binding Proteins