Semi-supervised learning for potential human microRNA-disease associations inference.

MicroRNAs play critical role in the development and progression of various diseases. Predicting potential miRNA-disease associations from vast amount of biological data is an important problem in the biomedical research. Considering the limitations in previous methods, we developed Regularized Least Squares for MiRNA-Disease Association (RLSMDA) to uncover the relationship between diseases and miRNAs. RLSMDA can work for diseases without known related miRNAs. Furthermore, it is a semi-supervised (does not need negative samples) and global method (prioritize associations for all the diseases simultaneously). Based on leave-one-out cross validation, reliable AUC have demonstrated the reliable performance of RLSMDA. We also applied RLSMDA to Hepatocellular cancer and Lung cancer and implemented global prediction for all the diseases simultaneously. As a result, 80% (Hepatocellular cancer) and 84% (Lung cancer) of top 50 predicted miRNAs and 75% of top 20 potential associations based on global prediction have been confirmed by biological experiments. We also applied RLSMDA to diseases without known related miRNAs in golden standard dataset. As a result, in the top 3 potential related miRNA list predicted by RLSMDA for 32 diseases, 34 disease-miRNA associations were successfully confirmed by experiments. It is anticipated that RLSMDA would be a useful bioinformatics resource for biomedical researches.