Interpretable Drug-to-Drug Network Features for Predicting Adverse Drug Reactions.

Recent years have witnessed booming data on drugs and their associated adverse drug reactions (ADRs). It was reported that these ADRs have resulted in a high hospitalisation rate worldwide. Therefore, a tremendous amount of research has been carried out to predict ADRs in the early phases of drug development, with the goal of reducing possible future risks. The pre-clinical and clinical phases of drug research can be time-consuming and cost-ineffective, so academics are looking forward to more extensive data mining and machine learning methods to be applied in this field of study. In this paper, we try to construct a drug-to-drug network based on non-clinical data sources. The network presents underlying relationships between drug pairs according to their common ADRs. Then, multiple node-level and graph-level network features are extracted from this network, e.g., weighted degree centrality, weighted PageRanks, etc. After concatenating the network features to the original drug features, they were fed into seven machine learning models, e.g., logistic regression, random forest, support vector machine, etc., and were compared to the baseline, where there were no network-based features considered. These experiments indicate that all the tested machine-learning methods would benefit from adding these network features. Among all these models, logistic regression (LR) had the highest mean AUROC score (82.1%) across all ADRs tested. Weighted degree centrality and weighted PageRanks were identified to be the most critical network features in the LR classifier. These pieces of evidence strongly indicate that the network approach can be vital in future ADR prediction, and this network-based approach could also be applied to other health informatics datasets.