Heterogeneous graph attention networks for drug virus association prediction.

Coronavirus Disease-19 (COVID-19) has lead global epidemics with high morbidity and mortality. However, there are currently no proven effective drugs targeting COVID-19. Identifying drug-virus associations can not only provide insights into the understanding of drug-virus interaction mechanism, but also guide and facilitate the screening of compound candidates for antiviral drug discovery. Since conventional experiment methods are time-consuming, laborious and expensive, computational methods to identify potential drug candidates for viruses (e.g., COVID-19) provide an alternative strategy. In this work, we propose a novel framework of Heterogeneous Graph Attention Networks for Drug-Virus Association predictions, named HGATDVA. First, we fully incorporate multiple sources of biomedical data, e.g., drug chemical information, virus genome sequences and viral protein sequences, to construct abundant features for drugs and viruses. Second, we construct two drug-virus heterogeneous graphs. For each graph, we design a self-enhanced graph attention network (SGAT) to explicitly model the dependency between a node and its local neighbors and derive the graph-specific representations for nodes. Third, we further develop a neural network architecture with tri-aggregator to aggregate the graph-specific representations to generate the final node representations. Extensive experiments were conducted on two datasets, i.e., DrugVirus and MDAD, and the results demonstrated that our model outperformed 7 state-of-the-art methods. Case study on SARS-CoV-2 validated the effectiveness of our model in identifying potential drugs for viruses.

Predicting human microbe-drug associations via graph convolutional network with conditional random field.

MOTIVATION: Human microbes play critical roles in drug development and precision medicine. How to systematically understand the complex interaction mechanism between human microbes and drugs remains a challenge nowadays. Identifying microbe-drug associations can not only provide great insights into understanding the mechanism, but also boost the development of drug discovery and repurposing. Considering the high cost and risk of biological experiments, the computational approach is an alternative choice. However, at present, few computational approaches have been developed to tackle this task. RESULTS: In this work, we leveraged rich biological information to construct a heterogeneous network for drugs and microbes, including a microbe similarity network, a drug similarity network and a microbe-drug interaction network. We then proposed a novel graph convolutional network (GCN)-based framework for predicting human Microbe-Drug Associations, named GCNMDA. In the hidden layer of GCN, we further exploited the Conditional Random Field (CRF), which can ensure that similar nodes (i.e. microbes or drugs) have similar representations. To more accurately aggregate representations of neighborhoods, an attention mechanism was designed in the CRF layer. Moreover, we performed a random walk with restart-based scheme on both drug and microbe similarity networks to learn valuable features for drugs and microbes, respectively. Experimental results on three different datasets showed that our GCNMDA model consistently achieved better performance than seven state-of-the-art methods. Case studies for three microbes including SARS-CoV-2 and two antimicrobial drugs (i.e. Ciprofloxacin and Moxifloxacin) further confirmed the effectiveness of GCNMDA in identifying potential microbe-drug associations. AVAILABILITY AND IMPLEMENTATION: Python codes and dataset are available at: https://github.com/longyahui/GCNMDA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.