Prediction of Human Cytochrome P450 Inhibition Using a Multitask Deep Autoencoder Neural Network

Molecular Pharmaceutics
Xiang LiJianfeng Pei

Abstract

Adverse side effects of drug-drug interactions induced by human cytochrome P450 (CYP450) inhibition is an important consideration in drug discovery. It is highly desirable to develop computational models that can predict the inhibitive effect of a compound against a specific CYP450 isoform. In this study, we developed a multitask model for concurrent inhibition prediction of five major CYP450 isoforms, namely, 1A2, 2C9, 2C19, 2D6, and 3A4. The model was built by training a multitask autoencoder deep neural network (DNN) on a large dataset containing more than 13 000 compounds, extracted from the PubChem BioAssay Database. We demonstrate that the multitask model gave better prediction results than that of single-task models, previous reported classifiers, and traditional machine learning methods on an average of five prediction tasks. Our multitask DNN model gave average prediction accuracies of 86.4% for the 10-fold cross-validation and 88.7% for the external test datasets. In addition, we built linear regression models to quantify how the other tasks contributed to the prediction difference of a given task between single-task and multitask models, and we explained under what conditions the multitask model will outperform the s...Continue Reading

References

May 1, 2002·JAMA : the Journal of the American Medical Association·Karen E LasserDavid H Bor
Oct 22, 2002·Lancet·Daniel W Nebert, David W Russell
Jul 16, 2003·Nature·Pamela A WilliamsHarren Jhoti
Aug 12, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Andrew WilliamsSimon E Ball
Oct 15, 2005·Nature Reviews. Drug Discovery·Larry C Wienkers, Timothy G Heath
Dec 15, 2005·The Journal of Biological Chemistry·Paul RowlandAngela M Bridges
Mar 28, 2006·Journal of Chemical Information and Modeling·Dumitru ErhanYoshua Bengio
Jun 13, 2006·Neural Computation·Geoffrey E HintonYee-Whye Teh
Jul 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·James IngleseChristopher P Austin
Feb 22, 2007·The Journal of Biological Chemistry·Stefaan SansenEric F Johnson
Jun 12, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·D F V Lewis, Y Ito
May 8, 2010·Antioxidants & Redox Signaling·Thomas C PochapskyMarina Dang
Mar 23, 2011·Journal of Computational Chemistry·Chun Wei Yap
Apr 16, 2011·Journal of Chemical Information and Modeling·Feixiong ChengYun Tang
Sep 13, 2011·Journal of Chemical Information and Modeling·Hongmao SunRuili Huang
Oct 11, 2011·Journal of Cheminformatics·Noel M O'BoyleGeoffrey R Hutchison
Aug 1, 2012·Bioinformatics·Pietro Di LenaPierre Baldi
Oct 11, 2012·Bioinformatics·Jesse Eickholt, Jianlin Cheng
Nov 3, 2012·The Journal of Biological Chemistry·R Leila ReynaldEric F Johnson
Jun 19, 2013·ACS Chemical Biology·Christian P KochGisbert Schneider
Jun 26, 2013·Journal of Chemical Information and Modeling·Alessandro LusciPierre Baldi
Oct 10, 2013·BMC Bioinformatics·Stephan BeiskenChristoph Steinbeck
Nov 7, 2014·PLoS Computational Biology·Marcin J SkwarkArne Elofsson
Jan 31, 2015·Journal of Chemical Information and Modeling·Junshui MaVladimir Svetnik
Jun 26, 2015·Journal of Chemical Information and Modeling·Bo-Han SuYufeng J Tseng
Jul 28, 2015·Nature Biotechnology·Babak AlipanahiBrendan J Frey
Oct 7, 2015·Journal of Chemical Information and Modeling·Youjun XuLuhua Lai
May 11, 2016·ACS Central Science·Tyler B HughesS Joshua Swamidass
Oct 1, 2016·Journal of Chemical Information and Modeling·Govindan SubramanianRajiah Aldrin Denny
Sep 6, 2017·Journal of Chemical Information and Modeling·Yuting XuVladimir Svetnik

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Citations

Nov 20, 2018·Expert Opinion on Drug Discovery·Yinqiu XuKejiang Lin
Sep 14, 2019·Annual Review of Pharmacology and Toxicology·Hao Zhu
Mar 18, 2020·Nucleic Acids Research·Priyanka BanerjeeRobert Preissner
Mar 30, 2020·Journal of Computer-aided Molecular Design·Anita Rácz, György M Keserű
Nov 14, 2020·Chemical Research in Toxicology·Marina Garcia de LomanaJohannes Kirchmair
Jan 14, 2021·Biotechnology and Bioprocess Engineering : BBE·Hyunho KimHojung Nam
Mar 20, 2020·Journal of Medicinal Chemistry·Jihui ZhaoMingyue Zheng
Jun 11, 2021·Molecular Diversity·Anita RáczKároly Héberger
Jul 14, 2021·Chemical Research in Toxicology·Xiaoxiao ZhangWeihua Li
Jan 8, 2019·Journal of Chemical Information and Modeling·Jan WenzelFriedemann Schmidt
Feb 5, 2019·Journal of Chemical Information and Modeling·Chuipu CaiFeixiong Cheng
Jul 17, 2020·Journal of Medicinal Chemistry·Chenjing CaiJianfeng Pei
Oct 12, 2019·Journal of Chemical Information and Modeling·Xiaoqi ShanDong-Qing Wei
Oct 22, 2021·Journal of Chemical Information and Modeling·Thanh-Hoang Nguyen-VoLy Le

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