Insplico: effective computational tool for studying splicing order of adjacent introns genome-wide with short and long RNA-seq reads
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- dc.contributor.author Gohr, André
- dc.contributor.author Iñiguez, Luis P.
- dc.contributor.author Torres Méndez, Antonio, 1992-
- dc.contributor.author Bonnal, Sophie
- dc.contributor.author Irimia Martínez, Manuel
- dc.date.accessioned 2023-07-19T06:34:19Z
- dc.date.available 2023-07-19T06:34:19Z
- dc.date.issued 2023
- dc.description.abstract Although splicing occurs largely co-transcriptionally, the order by which introns are removed does not necessarily follow the order in which they are transcribed. Whereas several genomic features are known to influence whether or not an intron is spliced before its downstream neighbor, multiple questions related to adjacent introns' splicing order (AISO) remain unanswered. Here, we present Insplico, the first standalone software for quantifying AISO that works with both short and long read sequencing technologies. We first demonstrate its applicability and effectiveness using simulated reads and by recapitulating previously reported AISO patterns, which unveiled overlooked biases associated with long read sequencing. We next show that AISO around individual exons is remarkably constant across cell and tissue types and even upon major spliceosomal disruption, and it is evolutionarily conserved between human and mouse brains. We also establish a set of universal features associated with AISO patterns across various animal and plant species. Finally, we used Insplico to investigate AISO in the context of tissue-specific exons, particularly focusing on SRRM4-dependent microexons. We found that the majority of such microexons have non-canonical AISO, in which the downstream intron is spliced first, and we suggest two potential modes of SRRM4 regulation of microexons related to their AISO and various splicing-related features. Insplico is available on gitlab.com/aghr/insplico.
- dc.description.sponsorship European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program [ERCCoG-LS2-101002275 to M.I.]; Spanish Ministry of Economy and Competitiveness [PID2020-115040GB-I00 to M.I.]; ‘Centro de Excelencia Severo Ochoa 2013–2017’ [SEV-2012-0208]. Funding for open access charge: European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program [ERCCoG-LS2-101002275 to M.I.].
- dc.format.mimetype application/pdf
- dc.identifier.citation Gohr A, Iñiguez LP, Torres-Mendez A, Bonnal S, Irimia M. Insplico: effective computational tool for studying splicing order of adjacent introns genome-wide with short and long RNA-seq reads. Nucleic Acids Res. 2023;51(10):e56. DOI: 10.1093/nar/gkad244
- dc.identifier.doi http://dx.doi.org/10.1093/nar/gkad244
- dc.identifier.issn 0305-1048
- dc.identifier.uri http://hdl.handle.net/10230/57611
- dc.language.iso eng
- dc.publisher Oxford University Press
- dc.relation.ispartof Nucleic Acids Res. 2023;51(10):e56
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/101002275
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-115040GB-I00
- dc.rights © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Computational methods
- dc.title Insplico: effective computational tool for studying splicing order of adjacent introns genome-wide with short and long RNA-seq reads
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion