Effect of molecular descriptor feature selection in support vector machine classification of pharmacokinetic and toxicological properties of chemical agents.

Statistical-learning methods have been developed for facilitating the prediction of pharmacokinetic and toxicological properties of chemical agents. These methods employ a variety of molecular descriptors to characterize structural and physicochemical properties of molecules. Some of these descriptors are specifically designed for the study of a particular type of properties or agents, and their use for other properties or agents might generate noise and affect the prediction accuracy of a statistical learning system. This work examines to what extent the reduction of this noise can improve the prediction accuracy of a statistical learning system. A feature selection method, recursive feature elimination (RFE), is used to automatically select molecular descriptors for support vector machines (SVM) prediction of P-glycoprotein substrates (P-gp), human intestinal absorption of molecules (HIA), and agents that cause torsades de pointes (TdP), a rare but serious side effect. RFE significantly reduces the number of descriptors for each of these properties thereby increasing the computational speed for their classification. The SVM prediction accuracies of P-gp and HIA are substantially increased and that of TdP remains unchanged by RFE. These prediction accuracies are comparable to those of earlier studies derived from a selective set of descriptors. Our study suggests that molecular feature selection is useful for improving the speed and, in some cases, the accuracy of statistical learning methods for the prediction of pharmacokinetic and toxicological properties of chemical agents. Copyright 2004 American Chemical Society