RPmirDIP: Reciprocal Perspective improves miRNA targeting prediction

MicroRNAs (miRNAs) are short, non-coding RNAs that interact with messenger RNA (mRNA) to accomplish critical cellular activities such as the regulation of gene expression. Several machine learning methods have been developed to improve classification accuracy and reduce validation costs by predicting which miRNA will target which gene. Application of these predictors to large numbers of unique miRNA-gene pairs has resulted in datasets comprising tens of millions of scored interactions; the largest among these is mirDIP. We here demonstrate that miRNA target prediction can be significantly improved (p<0.001) through the application of the Reciprocal Perspective (RP) method, a cascaded, semi-supervised machine learning method originally developed for protein-protein interaction prediction. The RP method, aptly named RPmirDIP, augments the original mirDIP prediction scores by leveraging local thresholds from the two complimentary views available to each miRNA-gene pair, rather than apply a traditional global decision threshold. Application of this novel RPmirDIP predictor promises to help identify new, unexpected miRNA-gene interactions. A dataset of RPmirDIP-scored interactions are made available to the scientific community at cu-bic.ca/RPmirDIP and 10.5683/SP2/LD8JKJ.