Variational graph auto-encoders for miRNA-disease association prediction.

Cumulative experimental studies have demonstrated the critical roles of microRNAs (miRNAs) in the diverse fundamental and important biological processes, and in the development of numerous complex human diseases. Thus, exploring the relationships between miRNAs and diseases is helpful with understanding the mechanisms, the detection, diagnosis, and treatment of complex diseases. As the identification of miRNA-disease associations via traditional biological experiments is time-consuming and expensive, an effective computational prediction method is appealing. In this study, we present a deep learning framework with variational graph auto-encoder for miRNA-disease association prediction (VGAE-MDA). VGAE-MDA first gets the representations of miRNAs and diseases from the heterogeneous networks constructed by miRNA-miRNA similarity, disease-disease similarity, and known miRNA-disease associations. Then, VGAE-MDA constructs two sub-networks: miRNA-based network and disease-based network. Combining the representations based on the heterogeneous network, two variational graph auto-encoders (VGAE) are deployed for calculating the miRNA-disease association scores from two sub-networks, respectively. Lastly, VGAE-MDA obtains the final predicted association score for a miRNA-disease pair by integrating the scores from these two trained networks. Unlike the previous model, the VGAE-MDA can mitigate the effect of noises from random selection of negative samples. Besides, the use of graph convolutional neural (GCN) network can naturally incorporate the node features from the graph structure while the variational autoencoder (VAE) makes use of latent variables to predict associations from the perspective of data distribution. The experimental results show that VGAE-MDA outperforms the state-of-the-art approaches in miRNA-disease association prediction. Besides, the effectiveness of our model has been further demonstrated by case studies.