title: A prediction model of drug-induced ototoxicity developed by an optimal support vector machine (SVM) method.
abstract: Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early stage of drug discovery. We thus, in this investigation, established an effective computational prediction model of drug-induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG-SVM. Three GA-CG-SVM models were developed based on three training sets containing agents bearing different risk levels of drug-induced ototoxicity. For comparison, models based on naïve Bayesian (NB) and recursive partitioning (RP) methods were also used on the same training sets. Among all the prediction models, the GA-CG-SVM model II showed the best performance, which offered prediction accuracies of 85.33% and 83.05% for two independent test sets, respectively. Overall, the good performance of the GA-CG-SVM model II indicates that it could be used for the prediction of drug-induced ototoxicity in the early stage of drug discovery.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, PR China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, PR China.
authors.forename: Guo-Bo
authors.initials: GB
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, PR China.
authors.forename: Lu-Yi
authors.initials: LY
authors.lastname: Huang
authors.affiliation: West China School of Pharmacy, Sichuan University, Sichuan 610041, PR China.
authors.forename: Huan-Zhang
authors.initials: HZ
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, PR China.
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, PR China.
authors.forename: Yu-Zong
authors.initials: YZ
authors.lastname: Chen
authors.affiliation: West China School of Pharmacy, Sichuan University, Sichuan 610041, PR China. Electronic address: ysylilinli@sina.com.
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, PR China. Electronic address: yangsy@scu.edu.cn.
authors.forename: Sheng-Yong
authors.initials: SY
authors.lastname: Yang
mesh_terms: D055808:Drug Discovery / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007759:Labyrinth Diseases / Q000139:chemically induced* / Q000378:metabolism; D008954:Models, Biological; D011237:Predictive Value of Tests; D060388:Support Vector Machine
keywords: Classification; Drug-induced ototoxicity; Naïve Bayesian; Recursive partitioning; Support vector machine