Drug side effect prediction through linear neighborhoods and multiple data source integration

Abstract

predicting drug side effects is a critical task in the drug discovery, which attracts great attentions in both academy and industry. Although lots of machine learning methods have been proposed, great challenges arise with boom of precision medicine. On one hand, many methods are based on the assumption that similar drugs may share same side effects, but measuring the drug-drug similarity appropriately is challenging. One the other hand, multi-source data provide diverse information for the analysis of side effects, and should be integrated for the high-accuracy prediction. In this paper, we tackle the side effect prediction problem through linear neighborhoods and multi-source data integration. In the feature space, linear neighborhoods are constructed to extract the drug-drug similarity, namely “linear neighborhood similarity”. By transferring the similarity into the side effect space, known side effect information is propagated through the similarity-based graph. Thus, we propose the linear neighborhood similarity method (LNSM), which utilizes single-source data for the side effect prediction. Further, we extend LNSM to deal with multi-source data, and propose two data integration methods: similarity matrix integration method (LNSM-SMI) and cost minimization integration method (LNSM-CMI), which integrate drug substructure data, drug target data, drug transporter data, drug enzyme data, drug pathway data and drug indication data to improve the prediction accuracy. The proposed methods are evaluated on the benchmark datasets. The linear neighborhood similarity method (LNSM) can produce satisfying results on the single-source data. Data integration methods (LNSM-SMI and LNSM-CMI) can effectively integrate multi-source data, and outperform other state-of-the-art side effect prediction methods in the cross validation and independent test. The proposed methods are promising for the drug side effect prediction.