DeepDrug: A general graph-based deep learning framework for drug relation prediction

Abstract

Computational approaches for accurate prediction of drug interactions, such as drug-drug interactions (DDIs) and drug-target interactions (DTIs), are highly demanded for biochemical researchers due to the efficiency and cost-effectiveness. Despite the fact that many methods have been proposed and developed to predict DDIs and DTIs respectively, their success is still limited due to a lack of systematic evaluation of the intrinsic properties embedded in the corresponding chemical structure. In this paper, we develop a deep learning framework, named DeepDrug, to overcome the above limitation by using residual graph convolutional networks (RGCNs) and convolutional networks (CNNs) to learn the comprehensive structural and sequential representations of drugs and proteins in order to boost the DDIs and DTIs prediction accuracy. We benchmark our methods in a series of systematic experiments, including binary-class DDIs, multi-class/multi-label DDIs, binary-class DTIs classification and DTIs regression tasks using several datasets. We then demonstrate that DeepDrug outperforms state-of-the-art methods in terms of both accuracy and robustness in predicting DDIs and DTIs with multiple experimental settings. Furthermore, we visualize the structural features learned by DeepDrug RGCN module, which displays compatible and accordant patterns in chemical properties and drug categories, providing additional evidence to support the strong predictive power of DeepDrug. Ultimately, we apply DeepDrug to perform drug repositioning on the whole DrugBank database to discover the potential drug candidates against SARS-CoV-2, where 3 out of 5 top-ranked drugs are reported to be repurposed to potentially treat COVID-19. To sum up, we believe that DeepDrug is an efficient tool in accurate prediction of DDIs and DTIs and provides a promising insight in understanding the underlying mechanism of these biochemical relations. The source code of the DeepDrug can be freely downloaded from https://github.com/wanwenzeng/deepdrug.