Predicting the Skin Sensitization Potential of Small Molecules with Machine Learning Models Trained on Biologically Meaningful Descriptors

In recent years a number of machine learning models for the prediction of the skin sensitization potential of small organic molecules have been reported and become available. These models generally perform well within their applicability domains but, as a result of the use of molecular fingerprints and other non-intuitive descriptors, the interpretability of the existing models is clearly limited. The aim of this work is to develop a strategy to replace the non-intuitive features by predicted outcomes of bioassays. We show that such replacement is indeed possible and that as few as ten interpretable, predicted bioactivities are sufficient to reach competitive performance. On a holdout data set of 257 compounds, the best model ("Skin Doctor CP:Bio") obtained an efficiency of 0.82 and an MCC of 0.52 (at the significance level of 0.20). Skin Doctor CP:Bio is available from the authors free of charge for academic research. The modeling strategies explored in this work are easily transferable and could be adopted for the development of more interpretable machine learning models for the prediction of the bioactivity and toxicity of small organic compounds.