Evidence map›Paper›PMID 40829803›Full record

ArticleNucleic acids research2025

MoDorado: enhanced detection of tRNA modifications in nanopore sequencing by off-label use of modification callers.

Franziskus N M Rübsam, Wang Liu-Wei, Yu Sun, Bhargesh Indravadan Patel, Wiep van der Toorn, Michael Piechotta, Christoph Dieterich, Max von Kleist, Ann E Ehrenhofer-Murray

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–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

15 citing papers in PubMed.

  1. Review
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  6. Review
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  8. Pseudouridylation landscape across 42bioRxiv : the preprint server for biology · 2026
    Article
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  10. Review
  11. Review
  12. 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

9 authors.

Franziskus N M RübsamInstitut für Biologie, Lebenswissenschaftliche Fakultät, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.
Wang Liu-WeiSystems Medicine of Infectious Disease (P5), Robert Koch Institute, 13353 Berlin, Germany.ORCID 0000-0002-9872-4140
Yu SunInstitut für Biologie, Lebenswissenschaftliche Fakultät, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.ORCID 0009-0000-1041-6593
Bhargesh Indravadan PatelInstitut für Biologie, Lebenswissenschaftliche Fakultät, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.
Wiep van der ToornSystems Medicine of Infectious Disease (P5), Robert Koch Institute, 13353 Berlin, Germany.
Michael PiechottaKlaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Christoph DieterichKlaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, 69120 Heidelberg, Germany.ORCID 0000-0001-9468-6311
Max von KleistSystems Medicine of Infectious Disease (P5), Robert Koch Institute, 13353 Berlin, Germany.
Ann E Ehrenhofer-MurrayInstitut für Biologie, Lebenswissenschaftliche Fakultät, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.ORCID 0000-0001-8709-1942

Funding

Chinese Scholarship CouncilDeutsche Forschungsgemeinschaft EH237/19-1Deutsche Forschungsgemeinschaft EH237/21-1Deutscher Akademischer AustauschdienstEuropean Union's Horizon 2020 research and innovation programGerman Ministry for Science and Education 01KI2016German RMaP consortium 439669440 TRR319 RMaP TP B01Germany's Excellence Strategy - The Berlin Mathematics Research Center MATH+ 390685689Germany's Excellence Strategy - The Berlin Mathematics Research Center MATH+ EXC-2046/1Humboldt-Universität zu BerlinMarieSklowska-Curie Actions Innovative Training Networks grant 955974
6 · The paper itself

Abstract

Rapid and accurate identification of transfer RNA (tRNA) modifications is crucial for understanding their role in protein translation and disease. However, their detection on tRNAs is challenging due to high modification density. With the release of the nanopore direct RNA sequencing kit SQK-RNA004, de novo modification calling models became available for pseudouridine (Ψ), m6A, inosine, and m5C, as part of the Dorado basecaller. By applying the Ψ model to tRNAs, we mapped both known and previously uncharacterized Ψ sites in Schizosaccharomyces pombe, and identified the corresponding pseudouridine synthases. This led to the discovery of two novel modification sites, Pus7-dependent Ψ8 and Pus1-dependent Ψ22. Furthermore, we have developed MoDorado, an algorithm to detect modifications beyond those used in model training ("off-label use"). It does so by assessing differences in modification predictions between modified and nonmodified samples using pre-trained, modification-specific models. By repurposing the Ψ/m6A/inosine/m5C models, MoDorado detected seven additional modifications (ncm5U, mcm5U, mcm5s2U, m7G, queuosine, m1A, and i6A), thus generating an expanded map of these tRNA modifications in S. pombe. This work provides a generalized framework for leveraging pre-trained models in determining the intricate landscape of tRNA modifications.

Indexed as

AlgorithmsNanopore SequencingRNA Processing, Post-TranscriptionalRNA, TransferIntramolecular TransferasesPseudouridineSchizosaccharomycesSchizosaccharomyces pombe ProteinsIntramolecular TransferasesPseudouridinepseudouridine synthasesRNA, TransferSchizosaccharomyces pombe Proteins

Identifiers

PMID40829803
PMCPMC12362250

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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.