TLHNMDA: Triple Layer Heterogeneous Network Based Inference for MiRNA-Disease Association Prediction.

In recent years, microRNAs (miRNAs) have been confirmed to be involved in many important biological processes and associated with various kinds of human complex diseases. Therefore, predicting potential associations between miRNAs and diseases with the huge number of verified heterogeneous biological datasets will provide a new perspective for disease therapy. In this article, we developed a novel computational model of Triple Layer Heterogeneous Network based inference for MiRNA-Disease Association prediction (TLHNMDA) by using the experimentally verified miRNA-disease associations, miRNA-long noncoding RNA (lncRNA) interactions, miRNA function similarity information, disease semantic similarity information and Gaussian interaction profile kernel similarity for lncRNAs into an triple layer heterogeneous network to predict new miRNA-disease associations. As a result, the AUCs of TLHNMDA are 0.8795 and 0.8795 ± 0.0010 based on leave-one-out cross validation (LOOCV) and 5-fold cross validation, respectively. Furthermore, TLHNMDA was implemented on three complex human diseases to evaluate predictive ability. As a result, 84% (kidney neoplasms), 78% (lymphoma) and 76% (prostate neoplasms) of top 50 predicted miRNAs for the three complex diseases can be verified by biological experiments. In addition, based on the HMDD v1.0 database, 98% of top 50 potential esophageal neoplasms-associated miRNAs were confirmed by experimental reports. It is expected that TLHNMDA could be a useful model to predict potential miRNA-disease associations with high prediction accuracy and stability.