CORAL: Binary classifications (active/inactive) for drug-induced liver injury.

INTRODUCTION

The data on human hepatotoxcity (drug-induced liver injury) is extremely important information from point of view of drug discovery. Experimental clinical data on this endpoint is scarce. Experimental way to extend databases on this endpoint is extremely difficult. Quantitative structure - activity relationships (QSAR) is attractive alternative of the experimental approach.

METHODS

Predictive models for human hepatotoxicity (drug-induced liver injury) have been built up by the Monte Carlo method with using of the CORAL software (http://www.insilico.eu/coral). These models are the binary classifications into active class and inactive class. These models are calculated with so-called "semi correlations" described in this work. The Mattews correlation coefficient of these models for external validation sets ranged from 0.52 to 0.62.

RESULTS DISCUSSION

The approach has been checked up with a group of random splits into the training and validation sets. These stochastic experiments have shown the stability of results: predictability of the models for various splits. Thus, the attempt to build up the classification QSAR model by means of the Monte Carlo technique, based on representation of the molecular structure via simplified molecular input line entry systems (SMILES) and hydrogen suppressed graph (HSG) using the CORAL software (http://www.insilico.eu/coral) has shown ability of this approach to provide quite good prediction of the examined endpoint (drug-induced liver injury).