In silico prediction of chemical neurotoxicity using machine learning

Abstract Neurotoxicity is one of the main causes of drug withdrawal, and the biological experimental methods of detecting neurotoxic toxicity are time-consuming and laborious. In addition, the existing computational prediction models of neurotoxicity still have some shortcomings. In response to these shortcomings, we collected a large number of data set of neurotoxicity and used PyBioMed molecular descriptors and eight machine learning algorithms to construct regression prediction models of chemical neurotoxicity. Through the cross-validation and test set validation of the models, it was found that the extra-trees regressor model had the best predictive effect on neurotoxicity (${q}_{\mathrm{test}}^2$ = 0.784). In addition, we get the applicability domain of the models by calculating the standard deviation distance and the lever distance of the training set. We also found that some molecular descriptors are closely related to neurotoxicity by calculating the contribution of the molecular descriptors to the models. Considering the accuracy of the regression models, we recommend using the extra-trees regressor model to predict the chemical autonomic neurotoxicity.