Prediction of Pharmacological and Xenobiotic Responses to Drugs Based on Time Course Gene Expression Profiles 英文参考文献.docVIP

PredictionofPharmacologicalandXenobioticResponses toDrugsBasedonTimeCourseGeneExpressionProfiles TaoHuang3,4.,WeiRenCui1,2.,LeLeHu1,KaiYanFeng4,Yi-XueLi3,4*,Yu-DongCai1* 1Institute of Systems Biology, Shanghai University, Shanghai, People’s Republic of China, 2Centre for Computational Systems Biology, Fudan University, Shanghai, People’sRepublicofChina,3KeyLaboratoryofSystemsBiology,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyofSciences,Shanghai,People’sRepublicof China,4ShanghaiCenterforBioinformationTechnology,Shanghai,People’sRepublicofChina Abstract Moreandmorepeopleareconcernedbytheriskofunexpectedsideeffectsobservedinthelaterstepsofthedevelopment ofnewdrugs,eitherinlateclinicaldevelopmentoraftermarketingapproval.Inordertoreducetheriskofthesideeffects,it is important to look out for the possible xenobiotic responses at an early stage. We attempt such an effort through a prediction by assuming that similarities in microarray profiles indicate shared mechanisms of action and/or toxicological responses among the chemicals being compared. A large time course microarray database derived from livers of compound-treated rats with thirty-four distinct pharmacological and toxicological responses were studied. The mRMR (Minimum-Redundancy-Maximum-Relevance) method and IFS (Incremental Feature Selection) were used to select a compact feature set (141 features) for the reduction of feature dimension and improvement of prediction performance. Withthese141features,theLeave-one-outcross-validationpredictionaccuracyoffirstorderresponseusingNNA(Nearest NeighborAlgorithm)was63.9%.Ourmethodcanbeusedforpharmacologicalandxenobioticresponsespredictionofnew compoundsandacceleratedrugdevelopment. Citation: Huang T, Cui W, HuL, Feng K, LiY-X, et al. (2009) Prediction of Pharmacological and Xenobiotic Responses to Drugs Based on Time Course Gene ExpressionProfiles.PLoSONE4(12):e8126.doi:10.1371/journal.pone.0008126 Editor:HanyA.El-Shemy,CairoUniversity,Egypt ReceivedSeptembe