Prediction of Adverse Drug Reactions by Combining Biomedical Tripartite Network and Graph Representation Model

As one of the primary contributors to high clinical attrition rates of drugs, toxicity evaluation is of critical significance to new drug discovery. Unsurprisingly, a vast number of computational methods have been developed at various stages of development pipeline to evaluate potential adverse drug reactions (ADRs). Despite previous success of these methods on individual ADR or certain drug family, there are great challenges to toxicity evaluation. In this study, a novel strategy was developed to predict the drug–ADR associations by combining deep learning and the biomedical tripartite network. This heterogeneous network contains biomedical linked data of three entities, for example, drugs, targets, and ADRs. For the first time, GraRep, a deep learning method for distributed representations, is introduced to learn graph representations and identify hidden features from the tripartite network which are further used for ADR prediction. Through this approach, drug–ADR associations could possibly be discovered from a systemic perspective. The accuracy of our method is 0.95 based on internal resource validation and 0.88 based on external resource validation. Moreover, our results show the prediction accuracy using the tripartite network is better than the one with bipartite network, suggesting the model performance can be improved with further enrichment on information. According to the result of 10-fold cross validation, the deep learning model outperforms two traditional methods (topology-based measures and chemical structure-based measures). Additionally, predictive models are also constructed using other deep learning methods, and comparable results are achieved. In summary, the biomedical tripartite network-based deep learning model proposed here proves to offer a promising solution for prediction of ADRs.