Screen of MicroRNA Targets in Zebrafish Using Heterogeneous Data Sources: A Case Study for Dre-miR-10 and Dre-miR-196

It has been established that microRNAs (miRNAs) play an important role in gene expres- sion by post-transcriptional regulation of messengerRNAs (mRNAs). However, the pre- cise relationships between microRNAs and their target genes in sense of numbers, types and biological relevance remain largely unclear. Dissecting the miRNA-target relation- ships will render more insights for miRNA targets identification and validation therefore promote the understanding of miRNA function. In miRBase, miRanda is the key algorithm used for target prediction for Zebrafish. This algorithm is high-throughput but brings lots of false positives (noise). Since validation of a large scale of targets through laboratory experiments is very time consuming, several computational methods for miRNA targets validation should be developed. In this chapter, we present an integrative method to inves- tigate several aspects of the relationships between miRNAs and their targets with the final purpose of extracting high confident targets from miRanda predicted targets pool. This is achieved by using the techniques ranging from statistical tests to clustering and association rules. Our research focuses on Zebrafish. It was found that validated targets do not neces- sarily associate with the highest sequence matching. Besides, for some miRNA families, the frequency of their predicted targets is significantly higher in the genomic region nearby their own physical location. Finally, in a case study of dre-miR-10 and dre-miR-196, it was found that the predicted target genes hoxd13a, hoxd11a, hoxd10a and hoxc4a of dre- miR-10 while hoxa9a, hoxc8a and hoxa13a of dre-miR-196 have similar characteristics as validated target genes and therefore represent high confidence target candidates.