Same computational analysis, different miRNA target predictions

To the editor:

Sethupathy et al.¹ compared various microRNA (miRNA) target-prediction programs and present a practical guide for predicting miRNA targets. The programs differ in their requirement for base-pairing of miRNA and target genes and implement similar but not the same criteria when cross-species conservation is applied. Consequently, these programs generate different sets of target genes for some, probably all, miRNAs. Sethupathy et al.¹ presented an online tool that takes sets of target genes predicted by the individual programs and presents compiled lists of the intersection of some programs, providing higher specificity, and the union of all programs, providing higher sensitivity for a particular miRNA (http://www.diana.pcbi.upenn.edu/cgi-bin/TargetCombo.cgi).

We used the same concept of intersection of some of the programs to obtain high specificity and a manageable number of target genes for subsequent experimental verification in the course of the research for one of our projects. We were particularly interested in miRNA has-miR-155 and some others, and we used only the new generation programs, namely PicTar, TargetScanS and miRanda. We noticed that the intersection of target gene sets we obtained for miR-155 differed strongly from that listed by Sethupathy et al.¹, with only one target in common (Supplementary Table 1 online). Similarly the list of intersections and unions of other miRNAs, for example, miR-146 and miR-16 differed (data not shown).

A possible explanation for this discrepancy is differences in the versions of the mentioned prediction programs. We searched the websites of MiRanda (http://cbio.mskcc.org/cgi-bin/mirnaviewer/mirnaviewer.pl), TargetScanS (http://genes.mit.edu/tscan/targetscanS2005.html) and PicTar (http://pictar.bio.nyu.edu/cgi-bin/new_PicTar_vertebrate.cgi) for miR-155 targets. We are not clear whether the lists of predictions we used were consistent with the precompiled ones mentioned by Sethupathy et al.¹.

Note: Supplementary information is available on the Nature Methods website.