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

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• dc.contributor.author Cruciani, Sonia
• dc.contributor.author Delgado-Tejedor, Anna
• dc.contributor.author Pryszcz, Leszek Piotr, 1985-
• dc.contributor.author Medina, Rebeca
• dc.contributor.author Llovera Nadal, Laia
• dc.contributor.author Novoa, Eva Maria
• dc.date.accessioned 2025-05-14T06:02:00Z
• dc.date.available 2025-05-14T06:02:00Z
• dc.date.issued 2025
• dc.description.abstract 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.
• dc.description.sponsorship 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cruciani S, Delgado-Tejedor A, Pryszcz LP, Medina R, Llovera L, Novoa EM. De novo basecalling of RNA modifications at single molecule and nucleotide resolution. Genome Biol. 2025 Feb 25;26(1):38. DOI: 10.1186/s13059-025-03498-6
• dc.identifier.doi http://dx.doi.org/10.1186/s13059-025-03498-6
• dc.identifier.issn 1474-7596
• dc.identifier.uri http://hdl.handle.net/10230/70384
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof Genome Biol. 2025 Feb 25;26(1):38
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/754422
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-128193NB-100
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101042103
• dc.rights © 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/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Basecalling
• dc.subject.keyword Machine learning
• dc.subject.keyword N6-methyladenosine
• dc.subject.keyword Nanopore sequencing
• dc.subject.keyword Native RNA
• dc.subject.keyword RNA modifications
• dc.subject.keyword Single molecule resolution
• dc.subject.keyword Training data
• dc.title De novo basecalling of RNA modifications at single molecule and nucleotide resolution
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion