Increasing evidences have indicated that microRNAs (miRNAs) are functionally associated with the development and progression of various complex human diseases. However, the roles of miRNAs in multiple biological processes or various diseases and their underlying molecular mechanisms still have not been fully understood yet. Predicting potential miRNA-disease associations by integrating various heterogeneous biological datasets is of great significance to the biomedical research. Computational methods could obtain potential miRNA-disease associations in a short time, which significantly reduce the experimental time and cost. Considering the limitations in previous computational methods, we developed the model of Within and Between Score for MiRNA-Disease Association prediction (WBSMDA) to predict potential miRNAs associated with various complex diseases. WBSMDA could be applied to the diseases without any known related miRNAs. The AUC of 0.8031 based on Leave-one-out cross validation has demonstrated its reliable performance. WBSMDA was further applied to Colon Neoplasms, Prostate Neoplasms, and Lymphoma for the identification of their potential related miRNAs. As a result, 90%, 84%, and 80% of predicted miRNA-disease pairs in the top 50 prediction list for these three diseases have been confirmed by recent experimental literatures, respectively. It is anticipated that WBSMDA would be a useful resource for potential miRNA-disease association identification.

Accumulating evidences have shown that plenty of miRNAs play fundamental and important roles in various biological processes and the deregulations of miRNAs are associated with a broad range of human diseases. However, the mechanisms underlying the dysregulations of miRNAs still have not been fully understood yet. All the previous computational approaches can only predict binary associations between diseases and miRNAs. Predicting multiple types of disease-miRNA associations can further broaden our understanding about the molecular basis of diseases in the level of miRNAs. In this study, the model of Restricted Boltzmann machine for multiple types of miRNA-disease association prediction (RBMMMDA) was developed to predict four different types of miRNA-disease associations. Based on this model, we could obtain not only new miRNA-disease associations, but also corresponding association types. To our knowledge, RBMMMDA is the first model which could computationally infer association types of miRNA-disease pairs. Leave-one-out cross validation was implemented for RBMMMDA and the AUC of 0.8606 demonstrated the reliable and effective performance of RBMMMDA. In the case studies about lung cancer, breast cancer, and global prediction for all the diseases simultaneously, 50, 42, and 45 out of top 100 predicted miRNA-disease association types were confirmed by recent biological experimental literatures, respectively.