MiRGOFS: a GO-based functional similarity measurement for miRNAs, with applications to the prediction of miRNA subcellular localization and miRNA-disease association

Motivation: Benefiting from high-throughput experimental technologies, whole-genome analysis of microRNAs (miRNAs) has been more and more common to uncover important regulatory roles of miRNAs and identify miRNA biomarkers for disease diagnosis. As a complementary information to the high-throughput experimental data, domain knowledge like the Gene Ontology and KEGG pathway is usually used to guide gene function analysis. However, functional annotation for miRNAs is scarce in the public databases. Till now, only a few methods have been proposed for measuring the functional similarity between miRNAs based on public annotation data, and these methods cover a very limited number of miRNAs, which are not applicable to large-scale miRNA analysis. Results: In this paper, we propose a new method to measure the functional similarity for miRNAs, called miRGOFS, which has two notable features: (i) it adopts a new GO semantic similarity metric which considers both common ancestors and descendants of GO terms; (i) it computes similarity between GO sets in an asymmetric manner, and weights each GO term by its statistical significance. The miRGOFS-based predictor achieves an F-1 of 61.2% on a benchmark dataset of miRNA localization, and AUC values of 87.7 and 81.1% on two benchmark sets of miRNA-disease association, respectively. Compared with the existing functional similarity measurements of miRNAs, miRGOFS has the advantages of higher accuracy and larger coverage of human miRNAs (over 1000 miRNAs).