REDDA: Integrating multiple biological relations to heterogeneous graph neural network for drug-disease association prediction

Computational drug repositioning is an effective way to find new indications for existing drugs, thus can accelerate drug development and reduce experimental costs. Recently, various deep learning-based repurposing methods have been established to identify the potential drug-disease associations (DDA). However, effective utilization of the relations of biological entities to capture the biological interactions to enhance the drug-disease association prediction is still challenging. To resolve the above problem, we proposed a heterogeneous graph neural network called REDDA (Relations-Enhanced Drug-Disease Association prediction). Assembled with three attention mechanisms, REDDA can sequentially learn drug/disease representations by a general heterogeneous graph convolutional network-based node embedding block, a topological subnet embedding block, a graph attention block, and a layer attention block. Performance comparisons on our proposed benchmark dataset show that REDDA outperforms 8 advanced drug-disease association prediction methods, achieving relative improvements of 0.76% on the area under the receiver operating characteristic curve (AUC) score and 13.92% on the precision-recall curve (AUPR) score compared to the suboptimal method. On the other benchmark dataset, REDDA also obtains relative improvements of 2.48% on the AUC score and 4.93% on the AUPR score. Specifically, case studies also indicate that REDDA can give valid predictions for the discovery of -new indications for drugs and new therapies for diseases. The overall results provide an inspiring potential for REDDA in the in silico drug development. The proposed benchmark dataset and source code are available in https://github.com/gu-yaowen/REDDA. •A large-scale benchmark for drug-disease association is proposed with 5 entities and 10 relations.•A Heterogeneous graph neural network is proposed for drug-disease association prediction called REDDA.•REDDA uses 3 attention mechanisms and a topological subnet to learn comprehensive node representations.•REDDA outperforms 8 advanced baselines and gain impressive improvements on 2 datasets.•Attention visualization analyzes and case study demonstrate the effectiveness of the model architecture of REDDA.