Dataset Information

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

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, miR-34a-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.

SUBMITTER: Oliveira AC

PROVIDER: S-EPMC5432626 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Oliveira Arthur C AC Bovolenta Luiz A LA Nachtigall Pedro G PG Herkenhoff Marcos E ME Lemke Ney N Pinhal Danillo D

Frontiers in genetics 20170516

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. W ...[more]

PMID: 28559915

Similar Datasets

Project description:MicroRNAs (miRNAs) are single-stranded non-coding RNAs known to regulate a wide range of cellular processes by silencing the gene expression at the protein and/or mRNA levels. Computational prediction of miRNA targets is essential for elucidating the detailed functions of miRNA. However, the prediction specificity and sensitivity of the existing algorithms are still poor to generate meaningful, workable hypotheses for subsequent experimental testing. Constructing a richer and more reliable training data set and developing an algorithm that properly exploits this data set would be the key to improve the performance current prediction algorithms.A comprehensive training data set is constructed for mammalian miRNAs with its positive targets obtained from the most up-to-date miRNA target depository called miRecords and its negative targets derived from 20 microarray data. A new algorithm SVMicrO is developed, which assumes a 2-stage structure including a site support vector machine (SVM) followed by a UTR-SVM. SVMicrO makes prediction based on 21 optimal site features and 18 optimal UTR features, selected by training from a comprehensive collection of 113 site and 30 UTR features. Comprehensive evaluation of SVMicrO performance has been carried out on the training data, proteomics data, and immunoprecipitation (IP) pull-down data. Comparisons with some popular algorithms demonstrate consistent improvements in prediction specificity, sensitivity and precision in all tested cases. All the related materials including source code and genome-wide prediction of human targets are available at http://compgenomics.utsa.edu/svmicro.html.A 2-stage SVM based new miRNA target prediction algorithm called SVMicrO is developed. SVMicrO is shown to be able to achieve robust performance. It holds the promise to achieve continuing improvement whenever better training data that contain additional verified or high confidence positive targets and properly selected negative targets are available.

Project description:BackgroundDeep-sequencing has enabled the identification of large numbers of miRNAs and siRNAs, making the high-throughput target identification a main limiting factor in defining their function. In plants, several tools have been developed to predict targets, majority of them being trained on Arabidopsis datasets. An extensive and systematic evaluation has not been made for their suitability for predicting targets in species other than Arabidopsis. Nor, these have not been evaluated for their suitability for high-throughput target prediction at genome level.ResultsWe evaluated the performance of 11 computational tools in identifying genome-wide targets in Arabidopsis and other plants with procedures that optimized score-cutoffs for estimating targets. Targetfinder was most efficient [89% 'precision' (accuracy of prediction), 97% 'recall' (sensitivity)] in predicting 'true-positive' targets in Arabidopsis miRNA-mRNA interactions. In contrast, only 46% of true positive interactions from non-Arabidopsis species were detected, indicating low 'recall' values. Score optimizations increased the 'recall' to only 70% (corresponding 'precision': 65%) for datasets of true miRNA-mRNA interactions in species other than Arabidopsis. Combining the results of Targetfinder and psRNATarget delivers high true positive coverage, whereas the intersection of psRNATarget and Tapirhybrid outputs deliver highly 'precise' predictions. The large number of 'false negative' predictions delivered from non-Arabidopsis datasets by all the available tools indicate the diversity in miRNAs-mRNA interaction features between Arabidopsis and other species. A subset of miRNA-mRNA interactions differed significantly for features in seed regions as well as the total number of matches/mismatches.ConclusionAlthough, many plant miRNA target prediction tools may be optimized to predict targets with high specificity in Arabidopsis, such optimized thresholds may not be suitable for many targets in non-Arabidopsis species. More importantly, non-conventional features of miRNA-mRNA interaction may exist in plants indicating alternate mode of miRNA target recognition. Incorporation of these divergent features would enable next-generation of algorithms to better identify target interactions.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets