Journal
PLOS ONE
Volume 6, Issue 2, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0017429
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Categories
Funding
- Canada Foundation for Innovation [12301, 203383]
- Canada Research Chair Program
- CIHR [202370]
- Natural Science and Engineering Research Council of Canada [104105]
- IBM
- Ontario Ministry of Health and Long Term Care (OMOHLTC)
- CIHR Canada
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Background: MicroRNAs are a class of small RNAs known to regulate gene expression at the transcript level, the protein level, or both. Since microRNA binding is sequence-based but possibly structure-specific, work in this area has resulted in multiple databases storing predicted microRNA: target relationships computed using diverse algorithms. We integrate prediction databases, compare predictions to in vitro data, and use cross-database predictions to model the microRNA: transcript interactome - referred to as the micronome - to study microRNA involvement in well-known signalling pathways as well as associations with disease. We make this data freely available with a flexible user interface as our microRNA Data Integration Portal - mirDIP (http://ophid.utoronto.ca/mirDIP). Results: mirDIP integrates prediction databases to elucidate accurate microRNA: target relationships. Using NAViGaTOR to produce interaction networks implicating microRNAs in literature-based, KEGG-based and Reactome-based pathways, we find these signalling pathway networks have significantly more microRNA involvement compared to chance (p < 0.05), suggesting microRNAs co-target many genes in a given pathway. Further examination of the micronome shows two distinct classes of microRNAs; universe microRNAs, which are involved in many signalling pathways; and intra-pathway microRNAs, which target multiple genes within one signalling pathway. We find universe microRNAs to have more targets (p < 0.0001), to be more studied (p < 0.0002), and to have higher degree in the KEGG cancer pathway (p < 0.0001), compared to intra-pathway microRNAs. Conclusions: Our pathway-based analysis of mirDIP data suggests microRNAs are involved in intra-pathway signalling. We identify two distinct classes of microRNAs, suggesting a hierarchical organization of microRNAs co-targeting genes both within and between pathways, and implying differential involvement of universe and intra-pathway microRNAs at the disease level.
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