Deep Learning Strategies For Rare Drug Mechanism of Action Prediction

The application of machine learning algorithms to predict the mechanism of action (MoA) of drugs can be highly valuable and enable the discovery of new uses for known molecules. The developed methods are usually evaluated with small subsets of MoAs with large support, leading to deceptively good generalization. However, these datasets may not accurately represent a practical use, due to the limited number of target MoAs. Accurate predictions for these rare drugs are important for drug discovery and should be a point of focus. In this work, we explore different training strategies to improve the performance of a well established deep learning model for rare drug MoA prediction. We explored transfer learning by first learning a model for common MoAs, and then using it to initialize the learning of another model for rarer MoAs. We also investigated the use of a cascaded methodology, in which results from an initial model are used as additional inputs to the model for rare MoAs. Finally, we proposed and tested an extension of Mixup data augmentation for multilabel classification. The baseline model showed an AUC of 73.2% for common MoAs and 62.4% for rarer classes. From the investigated methods, Mixup alone failed to improve the performance of a baseline classifier. Nonetheless, the other proposed methods outperformed the baseline for rare classes. Transfer Learning was preferred in predicting classes with less than 10 training samples, while the cascaded classifiers (with Mixup) showed better predictions for MoAs with more than 10 samples. However, the performance for rarer MoAs still lags behind the performance for frequent MoAs and is not sufficient for the reliable prediction of rare MoAs.