Evidence map›Paper›PMID 33305319›Full record

ArticleNucleic acids research2021

Validation of human microRNA target pathways enables evaluation of target prediction tools.

Fabian Kern, Lena Krammes, Karin Danz, Caroline Diener, Tim Kehl, Oliver Küchler, Tobias Fehlmann, Mustafa Kahraman, Stefanie Rheinheimer, Ernesto Aparicio-Puerta and 8 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 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

48 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  12. MicroRNA Gets a Mighty Award.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  13. Article
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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

18 authors.

Fabian KernChair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Lena KrammesInstitute of Human Genetics, Saarland University, 66421 Homburg, Germany.
Karin DanzDepartment of Bioprocessing & Bioanalytics, Fraunhofer Institute for Biomedical Engineering, 66280 Sulzbach, Germany.
Caroline DienerInstitute of Human Genetics, Saarland University, 66421 Homburg, Germany.
Tim KehlCenter for Bioinformatics, Saarland Informatics Campus, Saarland University, 66123 Saarbrücken, Germany.
Oliver KüchlerChair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Tobias FehlmannChair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Mustafa KahramanChair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Stefanie RheinheimerInstitute of Human Genetics, Saarland University, 66421 Homburg, Germany.
Ernesto Aparicio-PuertaChair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Sylvia WagnerDepartment of Bioprocessing & Bioanalytics, Fraunhofer Institute for Biomedical Engineering, 66280 Sulzbach, Germany.
Nicole LudwigInstitute of Human Genetics, Saarland University, 66421 Homburg, Germany.
Christina BackesChair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Hans-Peter LenhofCenter for Bioinformatics, Saarland Informatics Campus, Saarland University, 66123 Saarbrücken, Germany.
Hagen von BriesenDepartment of Bioprocessing & Bioanalytics, Fraunhofer Institute for Biomedical Engineering, 66280 Sulzbach, Germany.
Martin HartInstitute of Human Genetics, Saarland University, 66421 Homburg, Germany.
Andreas KellerChair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Eckart MeeseInstitute of Human Genetics, Saarland University, 66421 Homburg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MicroRNAs are regulators of gene expression. A wide-spread, yet not validated, assumption is that the targetome of miRNAs is non-randomly distributed across the transcriptome and that targets share functional pathways. We developed a computational and experimental strategy termed high-throughput miRNA interaction reporter assay (HiTmIR) to facilitate the validation of target pathways. First, targets and target pathways are predicted and prioritized by computational means to increase the specificity and positive predictive value. Second, the novel webtool miRTaH facilitates guided designs of reporter assay constructs at scale. Third, automated and standardized reporter assays are performed. We evaluated HiTmIR using miR-34a-5p, for which TNF- and TGFB-signaling, and Parkinson's Disease (PD)-related categories were identified and repeated the pipeline for miR-7-5p. HiTmIR validated 58.9% of the target genes for miR-34a-5p and 46.7% for miR-7-5p. We confirmed the targeting by measuring the endogenous protein levels of targets in a neuronal cell model. The standardized positive and negative targets are collected in the new miRATBase database, representing a resource for training, or benchmarking new target predictors. Applied to 88 target predictors with different confidence scores, TargetScan 7.2 and miRanda outperformed other tools. Our experiments demonstrate the efficiency of HiTmIR and provide evidence for an orchestrated miRNA-gene targeting.

Indexed as

High-Throughput Screening Assays1-Methyl-4-phenylpyridinium3' Untranslated RegionsCell LineCell Line, TumorGene Expression RegulationGenes, ReporterHumansMesencephalonMicroRNAsNeuroblastomaNeuronsParkinson DiseasePredictive Value of TestsSensitivity and SpecificitySignal Transduction1-Methyl-4-phenylpyridinium3' Untranslated RegionsMicroRNAsMIRN34 microRNA, humanMIRN7-1 microRNA, humanTransforming Growth Factor betaTumor Necrosis Factor-alpha

Identifiers

PMID33305319
PMCPMC7797041

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.