Combining Results from Distinct MicroRNA Target Prediction Tools Enhances the Performance of Analyses

Author(s)

Oliveira, Arthur C. ; Bovolenta, Luiz A. ; Nachtigall, Pedro G. ; Herkenhoff, Marcos E. ; Lemke, Ney ; Pinhal, Danillo

• Document type: Journal article
• Source: FRONTIERS IN GENETICS; v. 8, MAY 16 2017.
• Web of Science Citations: 11

Abstract

Target prediction is generally the first step toward recognition of bona fide microRNA (miRNA)-target interactions in living cells. Several target prediction tools are now available, which use distinct criteria and stringency to provide the best set of candidate targets for a single miRNA or a subset of miRNAs. However, there are many false-negative predictions, and consensus about the optimum strategy to select and use the output information provided by the target prediction tools is lacking. We compared the performance of four tools cited in literature-TargetScan (TS), miRanda-mirSVR (MR), Pita, and RNA22 (R22), and we determined the most effective approach for analyzing target prediction data (individual, union, or intersection). For this purpose, we calculated the sensitivity, specificity, precision, and correlation of these approaches using 10 miRNAs (miR-1-3p, miR-17-5p, miR-21-5p, miR-24-3p, miR-29a-3p, miR34a-5p, miR-124-3p, miR-125b-5p, miR-145-5p, and miR-155-5p) and 1,400 genes (700 validated and 700 non-validated) as targets of these miRNAs. The four tools provided a subset of high-quality predictions and returned few false-positive predictions; however, they could not identify several known true targets. We demonstrate that union of TS/MR and TS/MR/R22 enhanced the quality of in silico prediction analysis of miRNA targets. We conclude that the union rather than the intersection of the aforementioned tools is the best strategy for maximizing performance while minimizing the loss of time and resources in subsequent in vivo and in vitro experiments for functional validation of miRNA-target interactions. (AU)

• FAPESP's process: 12/13450-1 - Large scale exploratory analysis of Nile tilapia's miRNA expression using bioinformatics tools.
• Grantee: Luiz Augusto Bovolenta
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/19176-7 - Discovering variations and functions from non-coding Small RNAs in Oreochromis niloticus
• Grantee: Luiz Augusto Bovolenta
• Support type: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 14/03062-0 - Molecular characterization of heterotic hybrid from Red Stirling and Chitralada lines of Nile Tilapia (Oreochromis niloticus)
• Grantee: Marcos Edgar Herkenhoff
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/06864-7 - Functional analysis of microRNAs in cardiac development of fish species by RNA-Seq and reverse genetics
• Grantee: Pedro Gabriel Nachtigall
• Support type: Scholarships in Brazil - Doctorate