Toxicity prediction of small drug molecules of aryl hydrocarbon receptor using a proposed ensemble model

Abstract

Quantitative structure–activity relationships and quantitative structure–property relationships have provedtheir usefulness for predicting toxicities of drug molecules regarding their biological activities. In silico toxicity predictiontechniques are essential for reducing testing on rodents (in vivo) and for a less time-consuming and more cost-efficientalternative for the identification of toxic effects at an early stage of drug development. The authors aim to build aprediction model for better assessment of toxicity to quickly and efficiently test whether certain chemical compoundshave the potential to disrupt the processes in the human body that may adversely affect human health. Here, wehave proposed a computational method (in silico) for the toxicity prediction of small drug molecules using their variousphysicochemical properties (molecular descriptors) that can bind to the aryl hydrocarbon receptor. Pharmaceutical dataexploration laboratory software is used for extracting the features of drug molecules. The dataset of the aryl hydrocarbonreceptor contains 9008 drug molecules, where 1063 are active and 7945 are inactive, and each drug molecule contains1444 features. It is a novel prediction model based on ensemble learning that can efficiently classify active (binding)and inactive (nonbinding) compounds of the dataset. In our proposed ensemble model, we primarily performed featureselection using the Boruta library in R, after which we resolved the class imbalance problem itself by ensemble learningwhere we divided the dataset into seven data frames, which have approximately equal numbers of active and inactivedrug molecules. An ensemble model based upon the votes of seven random forest models is proposed, which gives anaccuracy of 93.76%. K-fold cross-validation is conducted to measure the consistency of the model. Finally, the validityof the proposed ensemble model for some drug molecules of acquired immune deficiency syndrome therapy and androgenreceptor has been proved.