Reexamining microRNA site accessibility in Drosophila: a population genomics study

Abstract

Kertesz et al. (Nature Genetics 2008) described PITA, a miRNA target prediction algorithm based on hybridization energy and site accessibility. In this note, we used a population genomics approach to reexamine their data and found that the PITA algorithm had lower specificity than methods based on evolutionary conservation at comparable levels of sensitivity.We also showed that deeply conserved miRNAs tend to have stronger hybridization energies to their targets than do other miRNAs. Although PITA had higher specificity in predicting targets than a naïve seed-match method, this signal was primarily due to the use of a single cutoff score for all miRNAs and to the observed correlation between conservation and hybridization energy. Overall, our results clarify the accuracy of different miRNA target prediction algorithms in Drosophila and the role of site accessibility in miRNA target prediction.

Figure 1. Substitution density in different classes of sites.

From left to right: 3′ UTR, miRNA seed matches (sequences in 3′ UTRs reverse-complementary to bases 1–7 or 2–8 of mature miRNAs), PITA sites (top 15000 sites ranked by ddG, 0/0 set), Pictar sites (S1 set), Accessibility conservation (conserved but not necessarily aligned sites with ddG<−7 in each of 4 species), Conserved 8mers (conserved and aligned in 4 species), Conserved Pictar sites (S1 anchors, i.e. only conserved S1 sites), Stark sites (Branch Length Score = 0.9).