Abstract
Recent trends in drug development have been marked by diminishing returns of escalating costs and falling rate of new drug approval. Unacceptable drug toxicity is a substantial cause of drug failure during clinical trials as well as the leading cause of drug withdraws after release to market. Computational methods capable of predicting these failures can reduce waste of resources and time devoted to the investigation of compounds that ultimately fail. We propose an original machine learning method that leverages identity of drug targets and off-targets, functional impact score computed from Gene Ontology annotations, and biological network data to predict drug toxicity. We demonstrate that our method (TargeTox) can distinguish potentially idiosyncratically toxic drugs from safe drugs and is also suitable for speculative evaluation of different target sets to support the design of optimal low-toxicity combinations.
