Evidence map›Paper›PMID 28148562›Full record

ArticleGenome research2017

microRNA target prediction programs predict many false positives.

Natalia Pinzón, Blaise Li, Laura Martinez, Anna Sergeeva, Jessy Presumey, Florence Apparailly, Hervé Seitz

Abstract read
In one paragraph

Article in Genome research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

153 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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93 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Natalia PinzónInstitut de Génétique Humaine, CNRS UPR 1142, 34396 Montpellier, France.
Blaise LiInstitut de Génétique Humaine, CNRS UPR 1142, 34396 Montpellier, France.ORCID 0000-0003-3080-1899
Laura MartinezInstitut de Génétique Humaine, CNRS UPR 1142, 34396 Montpellier, France.
Anna SergeevaInstitut de Génétique Humaine, CNRS UPR 1142, 34396 Montpellier, France.
Jessy PresumeyINSERM, U1183, IRMB, University Hospital St Éloi, 34295 Montpellier, France.
Florence ApparaillyINSERM, U1183, IRMB, University Hospital St Éloi, 34295 Montpellier, France.
Hervé SeitzInstitut de Génétique Humaine, CNRS UPR 1142, 34396 Montpellier, France.ORCID 0000-0001-8172-5393

Funding

MORPHINE AND ANALOGUES EFFECTS ON CELL METABOLISMR01DA000017 · NIDA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SIMON, ERIC J · 1985 to 2007
$2.0M
NEW PSYCHOMETRIC METHODS FOR SUBSTANCE ABUSE RESEARCHK05DA000017 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENTLER, PETER M · 1986 to 2012
$1.3M
NIDA NIH HHS K05 DA000017NIDA NIH HHS R01 DA000017
6 · The paper itself

Abstract

According to the current view, each microRNA regulates hundreds of genes. Computational tools aim at identifying microRNA targets, usually selecting evolutionarily conserved microRNA binding sites. While the false positive rates have been evaluated for some prediction programs, that information is rarely put forward in studies making use of their predictions. Here, we provide evidence that such predictions are often biologically irrelevant. Focusing on miR-223-guided repression, we observed that it is often smaller than inter-individual variability in gene expression among wild-type mice, suggesting that most predicted targets are functionally insensitive to that microRNA. Furthermore, we found that human haplo-insufficient genes tend to bear the most highly conserved microRNA binding sites. It thus appears that biological functionality of microRNA binding sites depends on the dose-sensitivity of their host gene and that, conversely, it is unlikely that every predicted microRNA target is dose-sensitive enough to be functionally regulated by microRNAs. We also observed that some mRNAs can efficiently titrate microRNAs, providing a reason for microRNA binding site conservation for inefficiently repressed targets. Finally, many conserved microRNA binding sites are conserved in a microRNA-independent fashion: Sequence elements may be conserved for other reasons, while being fortuitously complementary to microRNAs. Collectively, our data suggest that the role of microRNAs in normal and pathological conditions has been overestimated due to the frequent overlooking of false positive rates.

Indexed as

3' Untranslated RegionsAlgorithmsAnimalsBinding SitesComputational BiologyGene Expression RegulationHumansMiceMicroRNAsRNA, Messenger3' Untranslated RegionsMicroRNAsMIRN223 microRNA, mouseRNA, Messenger

Identifiers

PMID28148562
PMCPMC5287229

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.