Nucleic Acids Research Advance Access published online on November 11, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp926
Database Issue |
Patrocles: a database of polymorphic miRNA-mediated gene regulation in vertebrates
1Systems and Modeling, Montefiore Institute and 2Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Belgium
*To whom correspondence should be addressed. Tel: +32 4 366 41 51; Fax: +32 4 366 41 98; Email: michel.georges{at}ulg.ac.be
Received July 14, 2009. Revised September 18, 2009. Accepted October 9, 2009.
The Patrocles database (http://www.patrocles.org/) compiles DNA sequence polymorphisms (DSPs) that are predicted to perturb miRNA-mediated gene regulation. Distinctive features include: (i) the coverage of seven vertebrate species in its present release, aiming for more when information becomes available, (ii) the coverage of the three compartments involved in the silencing process (i.e. targets, miRNA precursors and silencing machinery), (iii) contextual information that enables users to prioritize candidate Patrocles DSPs, including graphical information on miRNA-target coexpression and eQTL effect of genotype on target expression levels, (iv) the inclusion of Copy Number Variants and eQTL information that affect miRNA precursors as well as genes encoding components of the silencing machinery and (v) a tool (Patrocles finder) that allows the user to determine whether her favorite DSP may perturb miRNA-mediated gene regulation of custom target sequences. To support the biological relevance of Patrocles' content, we searched for signatures of selection acting on Patrocles single nucleotide polymorphisms (pSNPs) in human and mice. As expected, we found a strong signature of purifying selection against not only SNPs that destroy conserved target sites but also against SNPs that create novel, illegitimate target sites, which is reminiscent of the Texel mutation in sheep.