A novel semi-supervised model for miRNA-disease association prediction based on ℓ₁-norm graph

Background: Identification of miRNA-disease associations has attracted much attention recently due to the functional roles of miRNAs implicated in various biological and pathological processes. Great efforts have been made to discover the potential associations between miRNAs and diseases both experimentally and computationally. Although reliable, the experimental methods are in general time-consuming and labor-intensive. In comparison, computational methods are more efficient and applicable to large-scale datasets. 

Methods: In this paper, we propose a novel semi-supervised model to predict miRNA-disease associations via ℓ₁-norm graph. Specifically, we first recalculate the miRNA functional similarities as well as the disease semantic similarities based on the latest version of MeSH descriptors and HMDD. We then update the similarity matrices and association matrix iteratively in both miRNA space and disease space. The optimized association matrices from each space are combined together as the final output. 


Results: Compared with four state-of-the-art prediction methods, our method achieved favorable performance with AUCs of 0.943 and 0.946 in both global LOOCV and local LOOCV, respectively. In addition, we carried out three types of case studies on five common human diseases, and most of the top 50 predicted miRNAs were confirmed to be associated with the investigated diseases by four databases dbDEMC, PheomiR, miR2Disease and miRwayDB. Specifically, our results provided potential evidence that miRNAs within the same family or cluster were likely to play functional roles together in given diseases. 


Conclusions: Taken together, the experimental results clearly demonstrated the utility of the proposed method. We anticipated that our method could serve as a reliable and efficient tool for miRNA-disease association prediction.