title: Target-Based Drug Repositioning Using Large-Scale Chemical-Protein Interactome Data.
abstract: Drug repositioning, or the identification of new indications for known drugs, is a useful strategy for drug discovery. In this study, we developed novel computational methods to predict potential drug targets and new drug indications for systematic drug repositioning using large-scale chemical-protein interactome data. We explored the target space of drugs (including primary targets and off-targets) based on chemical structure similarity and phenotypic effect similarity by making optimal use of millions of compound-protein interactions. On the basis of the target profiles of drugs, we constructed statistical models to predict new drug indications for a wide range of diseases with various molecular features. The proposed method outperformed previous methods in terms of interpretability, applicability, and accuracy. Finally, we conducted a comprehensive prediction of the drug-target-disease association network for 8270 drugs and 1401 diseases and showed biologically meaningful examples of newly predicted drug targets and drug indications. The predictive model is useful to understand the mechanisms of the predicted drug indications.
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 812-8582, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Sawada
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 812-8582, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology , 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mizutani
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 812-8582, Japan.|Institute for Advanced Study, Kyushu University , 6-10-1, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamanishi
mesh_terms: D057225:Data Mining; D055808:Drug Discovery; D058492:Drug Repositioning; D006801:Humans; D015233:Models, Statistical; D010641:Phenotype; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins