Prediction of drug induced liver injury using molecular and biological descriptors

Combinatorial Chemistry & High Throughput Screening
Christophe MullerAlexandre Varnek

Abstract

In this paper we report quantitative structure-activity models linking in vivo Drug-Induced Liver Injury (DILI) of organic molecules with some parameters both measured experimentally in vitro and calculated theoretically from the molecular structure. At the first step, a small database containing information of DILI in humans was created and annotated by experimentally observed information concerning hepatotoxic effects. Thus, for each compound a binary annotation "yes/no" was applied to DILI and seven endpoints causing different liver pathologies in humans: Cholestasis (CH), Oxidative Stress (OS), Mitochondrial injury (MT), Cirrhosis and Steatosis (CS), Hepatitis (HS), Hepatocellular (HC), and Reactive Metabolite (RM). Different machine-learning methods were used to build classification models linking DILI with molecular structure: Support Vector Machines, Artificial Neural Networks and Random Forests. Three types of models were developed: (i) involving molecular descriptors calculated directly from chemical structure, (ii) involving selected endpoints as "biological" descriptors, and (iii) involving both types of descriptors. It has been found that the models based solely on molecular descriptors have much weaker prediction p...Continue Reading

Citations

Feb 19, 2016·Biosensors & Bioelectronics·M S KumarA P Das
Oct 7, 2015·Journal of Chemical Information and Modeling·Youjun XuLuhua Lai
Feb 9, 2017·Journal of Chemical Information and Modeling·Eleni Kotsampasakou, Gerhard F Ecker
Apr 4, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Robert W YuchaMingxiang Liao
Jun 28, 2017·Toxicology·Eleni KotsampasakouGerhard F Ecker
Jul 27, 2017·Toxicological Research·Mark T D CroninJudith C Madden
May 1, 2021·Frontiers in Immunology·Sean HammondDean Naisbitt
Aug 22, 2021·Science Advances·Yu-Chiao ChiuYidong Chen
May 19, 2020·Molecular Pharmaceutics·Eni MineraliSean Ekins
Feb 11, 2020·Journal of Medicinal Chemistry·Merrie Mosedale, Paul B Watkins

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