Comparison of Multilabel and Single-Label Classification Applied to the Prediction of the Isoform Specificity of Cytochrome P450 Substrates

Each drug can potentially be metabolized by different CYP450 isoforms. In the development of new drugs, the prediction of the metabolic fate is important to prevent drug-drug interactions. In the present study, a collection of 580 CYP450 substrates is deeply analyzed by applying multi- and single-label classification strategies, after the computation and selection of suitable molecular descriptors. Cross-training with support vector machine, multilabel k-nearest-neighbor and counterpropagation neural network modeling methods were used in the multilabel approach, which allows one to classify the compounds simultaneously in multiple classes. In the single-label models, automatic variable selection was combined with various cross-validation experiments and modeling techniques. Moreover, the reliability of both multi- and single-label models was assessed by the prediction of an external test set. Finally, the predicted results of the best models were compared to show that, even if the models present similar performances, the multilabel approach more coherently reflects the real metabolism information