De novo basecalling of RNA modifications at single molecule and nucleotide resolution

RNA modifications influence RNA function and fate, but detecting them in individual molecules remains challenging for most modifications. Here we present a novel methodology to generate training sets and build modification-aware basecalling models. Using this approach, we develop the m6ABasecaller,...

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Autores: Cruciani, Sonia, Delgado-Tejedor, Anna, Pryszcz, Leszek Piotr, 1985-, Medina, Rebeca, Llovera Nadal, Laia, Novoa, Eva Maria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/70384
Acceso en línea:http://hdl.handle.net/10230/70384
http://dx.doi.org/10.1186/s13059-025-03498-6
Access Level:acceso abierto
Palabra clave:Basecalling
Machine learning
N6-methyladenosine
Nanopore sequencing
Native RNA
RNA modifications
Single molecule resolution
Training data
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spelling De novo basecalling of RNA modifications at single molecule and nucleotide resolutionCruciani, SoniaDelgado-Tejedor, AnnaPryszcz, Leszek Piotr, 1985-Medina, RebecaLlovera Nadal, LaiaNovoa, Eva MariaBasecallingMachine learningN6-methyladenosineNanopore sequencingNative RNARNA modificationsSingle molecule resolutionTraining dataRNA modifications influence RNA function and fate, but detecting them in individual molecules remains challenging for most modifications. Here we present a novel methodology to generate training sets and build modification-aware basecalling models. Using this approach, we develop the m6ABasecaller, a basecalling model that predicts m6A modifications from raw nanopore signals. We validate its accuracy in vitro and in vivo, revealing stable m6A modification stoichiometry across isoforms, m6A co-occurrence within RNA molecules, and m6A-dependent effects on poly(A) tails. Finally, we demonstrate that our method generalizes to other RNA and DNA modifications, paving the path towards future efforts detecting other modifications.SC was supported by “la Caixa” InPhINIT PhD fellowship (LCF/BQ/DI19/11730036). EMBO YIP Bridging Funds, and is currently supported by Centro de Excelencia Severo Ochoa funding. AD-T was supported by an FPI Severo-Ochoa fellowship by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC). LPP was supported by funding from the European Union’s H2020 research and innovation programme under Marie Sklodowska-Curie grant agreement No. 754422. This work was supported by the Spanish Ministry of Science, Innovation and Universities (MCIN/AEI/10.13039/501100011033/ FEDER, UEMEIC) (PID2021-128193NB-100 to EMN), the European Research Council (ERC-StG-2021 No 101042103 to EMN) and the Australian Research Council (DP180103571 to EMN). We acknowledge support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI /10.13039/501100011033), the Generalitat de Catalunya through the CERCA programme and to the EMBL partnership. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them.BioMed Central202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/70384http://dx.doi.org/10.1186/s13059-025-03498-6http://hdl.handle.net/10230/70384reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésGenome Biol. 2025 Feb 25;26(1):38info:eu-repo/grantAgreement/EC/H2020/754422info:eu-repo/grantAgreement/ES/3PE/PID2021-128193NB-100info:eu-repo/grantAgreement/EC/HE/101042103© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/703842026-05-29T05:05:01Z
dc.title.none.fl_str_mv De novo basecalling of RNA modifications at single molecule and nucleotide resolution
title De novo basecalling of RNA modifications at single molecule and nucleotide resolution
spellingShingle De novo basecalling of RNA modifications at single molecule and nucleotide resolution
Cruciani, Sonia
Basecalling
Machine learning
N6-methyladenosine
Nanopore sequencing
Native RNA
RNA modifications
Single molecule resolution
Training data
title_short De novo basecalling of RNA modifications at single molecule and nucleotide resolution
title_full De novo basecalling of RNA modifications at single molecule and nucleotide resolution
title_fullStr De novo basecalling of RNA modifications at single molecule and nucleotide resolution
title_full_unstemmed De novo basecalling of RNA modifications at single molecule and nucleotide resolution
title_sort De novo basecalling of RNA modifications at single molecule and nucleotide resolution
dc.creator.none.fl_str_mv Cruciani, Sonia
Delgado-Tejedor, Anna
Pryszcz, Leszek Piotr, 1985-
Medina, Rebeca
Llovera Nadal, Laia
Novoa, Eva Maria
author Cruciani, Sonia
author_facet Cruciani, Sonia
Delgado-Tejedor, Anna
Pryszcz, Leszek Piotr, 1985-
Medina, Rebeca
Llovera Nadal, Laia
Novoa, Eva Maria
author_role author
author2 Delgado-Tejedor, Anna
Pryszcz, Leszek Piotr, 1985-
Medina, Rebeca
Llovera Nadal, Laia
Novoa, Eva Maria
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Basecalling
Machine learning
N6-methyladenosine
Nanopore sequencing
Native RNA
RNA modifications
Single molecule resolution
Training data
topic Basecalling
Machine learning
N6-methyladenosine
Nanopore sequencing
Native RNA
RNA modifications
Single molecule resolution
Training data
description RNA modifications influence RNA function and fate, but detecting them in individual molecules remains challenging for most modifications. Here we present a novel methodology to generate training sets and build modification-aware basecalling models. Using this approach, we develop the m6ABasecaller, a basecalling model that predicts m6A modifications from raw nanopore signals. We validate its accuracy in vitro and in vivo, revealing stable m6A modification stoichiometry across isoforms, m6A co-occurrence within RNA molecules, and m6A-dependent effects on poly(A) tails. Finally, we demonstrate that our method generalizes to other RNA and DNA modifications, paving the path towards future efforts detecting other modifications.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/70384
http://dx.doi.org/10.1186/s13059-025-03498-6
http://hdl.handle.net/10230/70384
url http://hdl.handle.net/10230/70384
http://dx.doi.org/10.1186/s13059-025-03498-6
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Genome Biol. 2025 Feb 25;26(1):38
info:eu-repo/grantAgreement/EC/H2020/754422
info:eu-repo/grantAgreement/ES/3PE/PID2021-128193NB-100
info:eu-repo/grantAgreement/EC/HE/101042103
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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