title: Large-scale Direct Targeting for Drug Repositioning and Discovery.
abstract: A system-level identification of drug-target direct interactions is vital to drug repositioning and discovery. However, the biological means on a large scale remains challenging and expensive even nowadays. The available computational models mainly focus on predicting indirect interactions or direct interactions on a small scale. To address these problems, in this work, a novel algorithm termed weighted ensemble similarity (WES) has been developed to identify drug direct targets based on a large-scale of 98,327 drug-target relationships. WES includes: (1) identifying the key ligand structural features that are highly-related to the pharmacological properties in a framework of ensemble; (2) determining a drug's affiliation of a target by evaluation of the overall similarity (ensemble) rather than a single ligand judgment; and (3) integrating the standardized ensemble similarities (Z score) by Bayesian network and multi-variate kernel approach to make predictions. All these lead WES to predict drug direct targets with external and experimental test accuracies of 70% and 71%, respectively. This shows that the WES method provides a potential in silico model for drug repositioning and discovery.
authors.affiliation: Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Zihu
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Ziyin
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Materials Science and Chemical Engineering, Dalian University of Technology, Dalian, Liaoning, 116000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Xuetong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Ru
authors.affiliation: Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Piar
authors.initials: P
authors.lastname: Ali Shar
authors.affiliation: Department of Pathology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226. USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D055808:Drug Discovery; D058492:Drug Repositioning; D008024:Ligands; D015203:Reproducibility of Results; D064878:Web Browser
chemical_list: D008024:Ligands