Development of binary classification models for assessment of drug-induced liver injury in humans using a large set of FDA-approved drugs.

Drug-induced liver injury (DILI) has been identified as one of the major causes for drugs withdrawn from the market, and even termination during the late stages of development. Therefore, it is imperative to evaluate the DILI potential of lead compounds during the research and development process. Although various computational models have been developed to predict DILI, most of which applied the DILI data were extracted from preclinical sources. In this investigation, the in silico prediction models for DILI were constructed based on 1140 FDA-approved drugs by using naïve Bayes classifier approach. The genetic algorithm method was applied for the molecular descriptors selection. Among these established prediction models, the NB-11 model based on eight molecular descriptors combined with ECFP_18 showed the best prediction performance for DILI, which gave 91.7% overall prediction accuracy for the training set, and 68.9% concordance for the external test set. Therefore, the established NB-11 prediction model can be used as a reliable virtual screening tool to predict DILI adverse effect in the early stages of drug design. In addition, some new structural alters for DILI were identified, which could be used for structural optimization in the future drug design by medicinal chemists.