IDENTIFYING CO-REGULATING MICRORNA GROUPS

摘要

Background: Current miRNA target prediction tools have the common problem thattheir false positive rate is high. This renders identification of co-regulating groups ofmiRNAs and target genes unreliable. In this study, we describe a procedure to iden-tify highly probable co-regulating miRNAs and the corresponding co-regulated genegroups. Our procedure involves a sequence of statistical tests: (1) identify genes thatare highly probable miRNA targets; (2) determine for each such gene, the minimumnumber of miRNAs that co-regulate it with high probability; (3) find, for each suchgene, the combination of the determined minimum size of miRNAs that co-regulateit with the lowest p-value; and (4) discover for each such combination of miRNAs, thegroup of genes that are co-regulated by these miRNAs with the lowest p-value computedbased on GO term annotations of the genes. Results: Our method identifies 4, 3 and2-term miRNA groups that co-regulate gene groups of size at least 3 in human. Our resultsuggests some interesting hypothesis on the functional role of several miRNAs througha "guilt by association" reasoning. For example, miR-130, miR-19 and miR-101 areknown neurodegenerative diseases associated miRNAs. Our 3-term miRNA table showsthat miR-130/19/101 form a co-regulating group of rank 22 (p-value = 1.16 × 10~(-2)). Since miR-144 is co-regulating with miR-130, miR-19 and miR-101 of rank 4 (p-value =1.16 × 10~(-2)) in our 4-term miRNA table, this suggests hsa-miR-144 may be neurode-generative diseases related miRNA. Conclusions: This work identifies highly prob-able co-regulating miRNAs, which are refined from the prediction by computationaltools using (1) signal-to-noise ratio to get high accurate regulating miRNAs for everygene, and (2) Gene Ontology to obtain functional related co-regulating miRNA groups.Our result has partly been supported by biological experiments. Based on predictionby TargetScanS, we found highly probable target gene groups in the SupplementaryInformation. This result might help biologists to find small set of miRNAs for genesof interest rather than huge amount of miRNA set. Supplementary Information:https: //www.deakin.edu.au/~phoebe/JBCBAnChеп/JBCB.htm