Predicting miRNA-based disease-disease relationships through network diffusion on multi-omics biological data

With critical roles in regulating gene expression, miRNAs are strongly implicated in the pathophysiology of many complex diseases. Experimental methods to determine disease related miRNAs are time consuming and costly. Computationally predicting miRNA-disease associations has potential applications in finding miRNA therapeutic pathways and in understanding the role of miRNAs in disease-disease relationships. In this study, we propose the MiRNA-disease Association Prediction (MAP) method, an in-silico method to predict and prioritize miRNA-disease associations. The MAP method applies a network diffusion approach, starting from the known disease genes in a heterogenous network constructed from miRNA-gene associations, protein-protein interactions, and gene-disease associations. Validation using experimental data on miRNA-disease associations demonstrated superior performance to two current state-of-the-art methods, with areas under the ROC curve all over 0.8 for four types of cancer. MAP is successfully applied to predict differential miRNA expression in four cancer types. Most strikingly, disease-disease relationships in terms of shared miRNAs revealed hidden disease subtyping comparable to that of previous work on shared genes between diseases, with applications for multi-omics characterization of disease relationships.