Predicting drug–disease associations through layer attention graph convolutional network

Abstract Background: Determining drug–disease associations is an integral part in the process of drug development. However, the identification of drug–disease associations through wet experiments is costly and inefficient. Hence, the development of efficient and high-accuracy computational methods for predicting drug–disease associations is of great significance. Results: In this paper, we propose a novel computational method named as layer attention graph convolutional network (LAGCN) for the drug–disease association prediction. Specifically, LAGCN first integrates the known drug–disease associations, drug–drug similarities and disease–disease similarities into a heterogeneous network, and applies the graph convolution operation to the network to learn the embeddings of drugs and diseases. Second, LAGCN combines the embeddings from multiple graph convolution layers using an attention mechanism. Third, the unobserved drug–disease associations are scored based on the integrated embeddings. Evaluated by 5-fold cross-validations, LAGCN achieves an area under the precision–recall curve of 0.3168 and an area under the receiver–operating characteristic curve of 0.8750, which are better than the results of existing state-of-the-art prediction methods and baseline methods. The case study shows that LAGCN can discover novel associations that are not curated in our dataset. Conclusion: LAGCN is a useful tool for predicting drug–disease associations. This study reveals that embeddings from different convolution layers can reflect the proximities of different orders, and combining the embeddings by the attention mechanism can improve the prediction performances.