title: Systematic drug repositioning for a wide range of diseases with integrative analyses of phenotypic and molecular data.
abstract: Drug repositioning, or the application of known drugs to new indications, is a challenging issue in pharmaceutical science. In this study, we developed a new computational method to predict unknown drug indications for systematic drug repositioning in a framework of supervised network inference. We defined a descriptor for each drug-disease pair based on the phenotypic features of drugs (e.g., medicinal effects and side effects) and various molecular features of diseases (e.g., disease-causing genes, diagnostic markers, disease-related pathways, and environmental factors) and constructed a statistical model to predict new drug-disease associations for a wide range of diseases in the International Classification of Diseases. Our results show that the proposed method outperforms previous methods in terms of accuracy and applicability, and its performance does not depend on drug chemical structure similarity. Finally, we performed a comprehensive prediction of a drug-disease association network consisting of 2349 drugs and 858 diseases and described biologically meaningful examples of newly predicted drug indications for several types of cancers and nonhereditary diseases.
authors.affiliation: Division of System Cohort, Multi-Scale Research Center for Medical Science, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwata
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Sawada
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mizutani
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamanishi
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D015415:Biomarkers; D016000:Cluster Analysis; D057225:Data Mining; D004194:Disease / Q000145:classification / Q000235:genetics; D058492:Drug Repositioning / Q000379:methods*; D004777:Environment; D057166:High-Throughput Screening Assays; D006801:Humans; D038801:International Classification of Diseases; D009369:Neoplasms / Q000188:drug therapy; D016571:Neural Networks, Computer; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010641:Phenotype; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D004364:Pharmaceutical Preparations