Combining non-negative matrix factorization with graph Laplacian regularization for predicting drug-miRNA associations based on multi-source information fusion.

Increasing evidences suggest that miRNAs play a key role in the occurrence and progression of many complex human diseases. Therefore, targeting dysregulated miRNAs with small molecule drugs in the clinical has become a new treatment. Nevertheless, it is high cost and time-consuming for identifying miRNAs-targeted with drugs by biological experiments. Thus, more reliable computational method for identification associations of drugs with miRNAs urgently need to be developed. In this study, we proposed an efficient method, called GNMFDMA, to predict potential associations of drug with miRNA by combining graph Laplacian regularization with non-negative matrix factorization. We first calculated the overall similarity matrices of drugs and miRNAs according to the collected different biological information. Subsequently, the new drug-miRNA association adjacency matrix was reformulated based on the K nearest neighbor profiles so as to put right the false negative associations. Finally, graph Laplacian regularization collaborative non-negative matrix factorization was used to calculate the association scores of drugs with miRNAs. In the cross validation, GNMFDMA obtains AUC of 0.9193, which outperformed the existing methods. In addition, case studies on three common drugs (i.e., 5-Aza-CdR, 5-FU and Gemcitabine), 30, 31 and 34 of the top-50 associations inferred by GNMFDMA were verified. These results reveal that GNMFDMA is a reliable and efficient computational approach for identifying the potential drug-miRNA associations.

SPCMLMI: A structural perturbation-based matrix completion method to predict lncRNA-miRNA interactions.

Accumulating evidence indicated that the interaction between lncRNA and miRNA is crucial for gene regulation, which can regulate gene transcription, further affecting the occurrence and development of many complex diseases. Accurate identification of interactions between lncRNAs and miRNAs is helpful for the diagnosis and therapeutics of complex diseases. However, the number of known interactions of lncRNA with miRNA is still very limited, and identifying their interactions through biological experiments is time-consuming and expensive. There is an urgent need to develop more accurate and efficient computational methods to infer lncRNA-miRNA interactions. In this work, we developed a matrix completion approach based on structural perturbation to infer lncRNA-miRNA interactions (SPCMLMI). Specifically, we first calculated the similarities of lncRNA and miRNA, including the lncRNA expression profile similarity, miRNA expression profile similarity, lncRNA sequence similarity, and miRNA sequence similarity. Second, a bilayer network was constructed by integrating the known interaction network, lncRNA similarity network, and miRNA similarity network. Finally, a structural perturbation-based matrix completion method was used to predict potential interactions of lncRNA with miRNA. To evaluate the prediction performance of SPCMLMI, five-fold cross validation and a series of comparison experiments were implemented. SPCMLMI achieved AUCs of 0.8984 and 0.9891 on two different datasets, which is superior to other compared methods. Case studies for lncRNA XIST and miRNA hsa-mir-195-5-p further confirmed the effectiveness of our method in inferring lncRNA-miRNA interactions. Furthermore, we found that the structural consistency of the bilayer network was higher than that of other related networks. The results suggest that SPCMLMI can be used as a useful tool to predict interactions between lncRNAs and miRNAs.