Evidence map›Paper›PMID 34157120›Full record

ArticleNucleic acids research2021

Deep and accurate detection of m6A RNA modifications using miCLIP2 and m6Aboost machine learning.

Nadine Körtel, Cornelia Rücklé, You Zhou, Anke Busch, Peter Hoch-Kraft, F X Reymond Sutandy, Jacob Haase, Mihika Pradhan, Michael Musheev, Dirk Ostareck and 8 more

Open access · goldAbstract 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 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
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

76 citing papers in PubMed, 113 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. mArXiv · 2026
    Article
  9. RBM45 Preferential Binding to mThe journal of physical chemistry. B · 2026
    Article
  10. Review
  11. Review
  12. Article
  13. Systematic identification of tissue-conserved mbioRxiv : the preprint server for biology · 2026
    Article
  14. Article
  15. Targeting intracellular mRNA mJournal of advanced research · 2026
    Review
  16. Review
  17. Review
  18. Article
  19. RMzyme: regulations of RNA-modifying enzymes in humans.Signal transduction and targeted therapy · 2026
    Article
  20. Meta-unstable mRNAs in activated CD8Nature communications · 2026
    Article

16 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

18 authors at 6 institutions in 2 countries.

Nadine KörtelInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Cornelia RückléInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
You ZhouBuchmann Institute for Molecular Life Sciences (BMLS) & Faculty of Biological Sciences, Goethe University Frankfurt, Frankfurt 60438, Germany.
Anke BuschInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Peter Hoch-KraftInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
F X Reymond SutandyInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Jacob HaaseInstitute of Molecular Medicine, Sect. Molecular Cell Biology, Martin Luther University Halle-Wittenberg, Charles Tanford Protein Center, Halle 06120, Germany.
Mihika PradhanInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Michael MusheevInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Dirk OstareckDepartment of Intensive Care Medicine, University Hospital RWTH Aachen, Aachen 52074, Germany.
Antje Ostareck-LedererDepartment of Intensive Care Medicine, University Hospital RWTH Aachen, Aachen 52074, Germany.ORCID 0000-0003-0733-7071
Christoph DieterichKlaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, Heidelberg 69120, Germany.ORCID 0000-0001-9468-6311
Stefan HüttelmaierInstitute of Molecular Medicine, Sect. Molecular Cell Biology, Martin Luther University Halle-Wittenberg, Charles Tanford Protein Center, Halle 06120, Germany.ORCID 0000-0001-9335-4227
Christof NiehrsInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Oliver RauschSTORM Therapeutics Ltd, Cambridge CB22 3AT, UK.
Dan DominissiniCancer Research Center and Wohl Institute for Translational Medicine, Chaim Sheba Medical Center, Tel HaShomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
Julian KönigInstitute of Molecular Biology (IMB), Mainz 55128, Germany.ORCID 0000-0002-9398-5421
Kathi ZarnackBuchmann Institute for Molecular Life Sciences (BMLS) & Faculty of Biological Sciences, Goethe University Frankfurt, Frankfurt 60438, Germany.ORCID 0000-0003-3527-3378
Institute of Molecular Biology · DEGoethe University Frankfurt · DEHeidelberg University · DEMartin Luther University Halle-Wittenberg · DERWTH Aachen University · DETel Aviv University · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic mRNAs and influences many aspects of RNA processing. miCLIP (m6A individual-nucleotide resolution UV crosslinking and immunoprecipitation) is an antibody-based approach to map m6A sites with single-nucleotide resolution. However, due to broad antibody reactivity, reliable identification of m6A sites from miCLIP data remains challenging. Here, we present miCLIP2 in combination with machine learning to significantly improve m6A detection. The optimized miCLIP2 results in high-complexity libraries from less input material. Importantly, we established a robust computational pipeline to tackle the inherent issue of false positives in antibody-based m6A detection. The analyses were calibrated with Mettl3 knockout cells to learn the characteristics of m6A deposition, including m6A sites outside of DRACH motifs. To make our results universally applicable, we trained a machine learning model, m6Aboost, based on the experimental and RNA sequence features. Importantly, m6Aboost allows prediction of genuine m6A sites in miCLIP2 data without filtering for DRACH motifs or the need for Mettl3 depletion. Using m6Aboost, we identify thousands of high-confidence m6A sites in different murine and human cell lines, which provide a rich resource for future analysis. Collectively, our combined experimental and computational methodology greatly improves m6A identification.

Indexed as

Machine LearningRNA Processing, Post-TranscriptionalAdenosineAnimalsHEK293 CellsHumansMethyltransferasesMiceMouse Embryonic Stem CellsNucleotide MotifsRNA, MessengerRNA-SeqSensitivity and SpecificityAdenosineMethyltransferasesMETTL3 protein, humanN-methyladenosineRNA, Messenger

Identifiers

PMID34157120
PMCPMC8450095
OpenAlexW3174760894

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.