Inferring MicroRNA-Disease Associations by Random Walk on a Heterogeneous Network with Multiple Data Sources

Since the discovery of the regulatory function of microRNA (miRNA), increased attention has focused on identifying the relationship between miRNA and disease. It has been suggested that computational method is an efficient way to identify potential disease-related miRNAs for further confirmation using biological experiments. In this paper, we first highlighted three limitations commonly associated with previous computational methods. To resolve these limitations, we established disease similarity subnetwork and miRNA similarity subnetwork by integrating multiple data sources, where the disease similarity is composed of disease semantic similarity and disease functional similarity, and the miRNA similarity is calculated using the miRNA-target gene and miRNA-lncRNA (long non-coding RNA) associations. Then, a heterogeneous network was constructed by connecting the disease similarity subnetwork and the miRNA similarity subnetwork using the known miRNA-disease associations. We extended random walk with restart to predict miRNA-disease associations in the heterogeneous network. The leave-one-out cross-validation achieved an average area under the curve (AUC) of 0.8049 across 341 diseases and 476 miRNAs. For five-fold cross-validation, our method achieved an AUC from 0.7970 to 0.9249 for 15 human diseases. Case studies further demonstrated the feasibility of our method to discover potential miRNA-disease associations. An online service for prediction is freely available at http://ifmda.aliapp.com.