HLGNN-MDA: Heuristic Learning Based on Graph Neural Networks for miRNA-Disease Association Prediction.

Identifying disease-related miRNAs can improve the understanding of complex diseases. However, experimentally finding the association between miRNAs and diseases is expensive in terms of time and resources. The computational screening of reliable miRNA-disease associations has thus become a necessary tool to guide biological experiments. "Similar miRNAs will be associated with the same disease" is the assumption on which most current miRNA-disease association prediction methods rely; however, biased prior knowledge, and incomplete and inaccurate miRNA similarity data and disease similarity data limit the performance of the model. Here, we propose heuristic learning based on graph neural networks to predict microRNA-disease associations (HLGNN-MDA). We learn the local graph topology features of the predicted miRNA-disease node pairs using graph neural networks. In particular, our improvements to the graph convolution layer of the graph neural network enable it to learn information among homogeneous nodes and among heterogeneous nodes. We illustrate the performance of HLGNN-MDA by performing tenfold cross-validation against excellent baseline models. The results show that we have promising performance in multiple metrics. We also focus on the role of the improvements to the graph convolution layer in the model. The case studies are supported by evidence on breast cancer, hepatocellular carcinoma and renal cell carcinoma. Given the above, the experiments demonstrate that HLGNN-MDA can serve as a reliable method to identify novel miRNA-disease associations.