Prediction of Disease-related microRNAs through Integrating Attributes of microRNA Nodes and Multiple Kinds of Connecting Edges

Abstract

Identifying disease-associated microRNAs (disease miRNAs) contributes to the understanding of disease pathogenesis. Most previous computational biology studies focused on multiple kinds of connecting edges of miRNAs and diseases, including miRNA–miRNA similarities, disease–disease similarities, and miRNA–disease associations. Few methods exploited the node attribute information related to miRNA family and cluster. The previous methods do not completely consider the sparsity of node attributes. Additionally, it is challenging to deeply integrate the node attributes of miRNAs and the similarities and associations related to miRNAs and diseases. In the present study, we propose a novel method, known as MDAPred, based on nonnegative matrix factorization to predict candidate disease miRNAs. MDAPred integrates the node attributes of miRNAs and the related similarities and associations of miRNAs and diseases. Since a miRNA is typically subordinate to a family or a cluster, the node attributes of miRNAs are sparse. Similarly, the data for miRNA and disease similarities are sparse. Projecting the miRNA and disease similarities and miRNA node attributes into a common low-dimensional space contributes to estimating miRNA-disease associations. Simultaneously, the possibility that a miRNA is associated with a disease depends on the miRNA’s neighbour information. Therefore, MDAPred deeply integrates projections of multiple kinds of connecting edges, projections of miRNAs node attributes, and neighbour information of miRNAs. The cross-validation results showed that MDAPred achieved superior performance compared to other state-of-the-art methods for predicting disease-miRNA associations. MDAPred can also retrieve more actual miRNA-disease associations at the top of prediction results, which is very important for biologists. Additionally, case studies of breast, lung, and pancreatic cancers further confirmed the ability of MDAPred to discover potential miRNA–disease associations.