title: Large-Scale Prediction of Beneficial Drug Combinations Using Drug Efficacy and Target Profiles.
abstract: The identification of beneficial drug combinations is a challenging issue in pharmaceutical and clinical research toward combinatorial drug therapy. In the present study, we developed a novel computational method for large-scale prediction of beneficial drug combinations using drug efficacy and target profiles. We designed an informative descriptor for each drug-drug pair based on multiple drug profiles representing drug-targeted proteins and Anatomical Therapeutic Chemical Classification System codes. Then, we constructed a predictive model by learning a sparsity-induced classifier based on known drug combinations from the Orange Book and KEGG DRUG databases. Our results show that the proposed method outperforms the previous methods in terms of the accuracy of high-confidence predictions, and the extracted features are biologically meaningful. Finally, we performed a comprehensive prediction of novel drug combinations for 2,639 approved drugs, which predicted 142,988 new potentially beneficial drug-drug pairs. We showed several examples of successfully predicted drug combinations for a variety of 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.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: Ryusuke
authors.initials: R
authors.lastname: Sawada
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: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology , 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kotera
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.|Institute for Advanced Study, Kyushu University , 6-10-1, Hakozaki, Higashi-ku, Fukuoka, Fukuoka 812-8581, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamanishi
mesh_terms: D019295:Computational Biology; D062313:Databases, Pharmaceutical; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004347:Drug Interactions; D058492:Drug Repositioning; D006801:Humans; D012044:Regression Analysis
chemical_list: D004338:Drug Combinations