ComNet: A Multiview Deep Learning Model for Predicting Drug Combination Side Effects.

Abstract

As combination therapy becomes more common in clinical applications, predicting adverse effects of combination medications is a challenging task. However, there are three limitations of the existing prediction models. First, they rely on a single view of the drug and cannot fully utilize multiview information, resulting in limited performance when capturing complex structures. Second, they ignore subgraph information at different scales, which limits the ability to model interactions between subgraphs. Third, there has been limited research on effectively integrating multiview features of molecules. Therefore, we propose ComNet, a deep learning model that improves the accuracy of side effect prediction by integrating multiview features of drugs. First, to capture diverse features of drugs, a multiview feature extraction module is proposed, which not only uses molecular fingerprints but also extracts semantic information on SMILES and spatial information on 3D conformations. Second, to enhance the modeling ability of complex structures, a multiscale subgraph fusion mechanism is proposed, which can fuse local and global graph structures of drugs. Finally, a multiview feature fusion mechanism is proposed, which uses an attention mechanism to adaptively adjust the weights of different views to achieve multiview data fusion. Experiments on several publicly available data sets show that ComNet performs better than existing methods in various complex scenarios, especially in cold-start scenarios. Ablation experiments show that each core structure in ComNet contributes to the overall performance. Further analysis shows that ComNet not only converges rapidly and has good generalization ability but also identifies different substructures in the molecule. Finally, a case study on a self-collected data set validates the superior performance of ComNet in practical applications.