miRNA target prediction through mining of miRNA relationships

miRNAs are small regulators that mediate gene expression and each miRNA regulates specific target genes. In animals, target prediction of the miRNAs is accomplished through several computational methods, i.e. miRanda, TargetScan and PicTar. Typically, these methods predict targets from features of miRNA-target interaction such as sequence complementarity, free energy of RNA duplexes and conservation of target sites. They are constructed for high throughput and also result in a large amount of predictions and a high estimated false-positive rate. To date, specific rules to capture all known miRNA targets have not been devised. We observed that miRNAs sometimes share targets. Therefore, in this paper we present an approach which analyzes miRNA-miRNA relationships and utilizes them for target prediction.We use machine learning techniques to reveal the feature patterns between known miRNAs. Different data setups are evaluated and compared to achieve the best performance. Furthermore, the derived rules are applied to miRNAs of which the targets are not yet known so as to see if new targets could be predicted. In the analysis of functionally similar miRNAs, we found that genomic distance and seed similarity between miRNAs are dominant features in the description of a group of miRNAs binding the same target. Application of one specific rule resulted in the prediction of targets for seven miRNAs for which the targets were formerly unknown. Some of these targets were also detected by the existing methods. Our method contributes to the improvement of target identification by predicting targets with high specificity and without conservation limitation.

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