SCMFMDA: Predicting microRNA-disease associations based on similarity constrained matrix factorization

miRNAs belong to small non-coding RNAs that are related to a number of complicated biological processes. Considerable studies have suggested that miRNAs are closely associated with many human diseases. In this study, we proposed a computational model based on Similarity Constrained Matrix Factorization for miRNA-Disease Association Prediction (SCMFMDA). In order to effectively combine different disease and miRNA similarity data, we applied similarity network fusion algorithm to obtain integrated disease similarity (composed of disease functional similarity, disease semantic similarity and disease Gaussian interaction profile kernel similarity) and integrated miRNA similarity (composed of miRNA functional similarity, miRNA sequence similarity and miRNA Gaussian interaction profile kernel similarity). In addition, the L-2 regularization terms and similarity constraint terms were added to traditional Nonnegative Matrix Factorization algorithm to predict disease-related miRNAs. SCMFMDA achieved AUCs of 0.9675 and 0.9447 based on global Leave-one-out cross validation and five-fold cross validation, respectively. Furthermore, the case studies on two common human diseases were also implemented to demonstrate the prediction accuracy of SCMFMDA. The out of top 50 predicted miRNAs confirmed by experimental reports that indicated SCMFMDA was effective for prediction of relationship between miRNAs and diseases. Author summary Considerable studies have suggested that miRNAs are closely associated with many human diseases, so predicting potential associations between miRNAs and diseases can contribute to the diagnose and treatment of diseases. Several models of discovering unknown miRNA-diseases associations make the prediction more productive and effective. We proposed SCMFMDA to obtain more accuracy prediction result by applying similarity network fusion to fuse multi-source disease and miRNA information and then utilizing similarity constrained matrix factorization to make prediction based on biological information. The global Leave-one-out cross validation and five-fold cross validation were applied to evaluate our model. Consequently, SCMFMDA could achieve AUCs of 0.9675 and 0.9447 that were obviously higher than previous computational models. Furthermore, we implemented case studies on significant human diseases including colon neoplasms and lung neoplasms, 47 and 46 of top-50 were confirmed by experimental reports. All results proved that SCMFMDA could be regard as an effective way to discover unverified connections of miRNA-disease.

Automated summary

miRNAs are closely related to many human diseases, and predicting potential associations between miRNAs and diseases is important for disease diagnosis and treatment. SCMFMDA, which fuses multi-source disease and miRNA information using similarity network fusion and utilizes similarity constrained matrix factorization for prediction, achieves more accurate prediction results. Evaluated through global Leave-one-out cross validation and five-fold cross validation, SCMFMDA achieves higher AUCs compared to previous computational models. Case studies on significant human diseases confirm the effectiveness of SCMFMDA in discovering unverified connections between miRNAs and diseases.