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Prediction of alternative pre-mRNA splicing outcomes

To understand the biological impact of alternative pre-mRNA splicing, it is vital to know which exons are involved, what protein domains they encode, and how the translated isoforms differ. Therefore, we developed a computational pipeline (RiboSplitter) focused on functional effect prediction. It bu...

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Autores principales: Najjar, Rayan, Mustelin, Tomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651857/
https://www.ncbi.nlm.nih.gov/pubmed/37968320
http://dx.doi.org/10.1038/s41598-023-47348-6
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author Najjar, Rayan
Mustelin, Tomas
author_facet Najjar, Rayan
Mustelin, Tomas
author_sort Najjar, Rayan
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description To understand the biological impact of alternative pre-mRNA splicing, it is vital to know which exons are involved, what protein domains they encode, and how the translated isoforms differ. Therefore, we developed a computational pipeline (RiboSplitter) focused on functional effect prediction. It builds on event-based alternative splicing detection with additional filtering steps leading to more efficient statistical testing, and with detection of isoform-specific protein changes. A key methodological advance is reading frame prediction by translating exonic DNA in all possible frames, then finding a single open reading frame, or a single frame with matches to known proteins of the gene. This allowed unambiguous translation in 93.9% of alternative splicing events when tested on RNA-sequencing data of B cells from Sjögren’s syndrome patients. RiboSplitter does not depend on reference annotations and translates events even when one or both isoform(s) are novel (unannotated). RiboSplitter’s visualizations illustrate each event with translation outcomes, show event location within the gene, and align exons to protein domains.
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spelling pubmed-106518572023-11-15 Prediction of alternative pre-mRNA splicing outcomes Najjar, Rayan Mustelin, Tomas Sci Rep Article To understand the biological impact of alternative pre-mRNA splicing, it is vital to know which exons are involved, what protein domains they encode, and how the translated isoforms differ. Therefore, we developed a computational pipeline (RiboSplitter) focused on functional effect prediction. It builds on event-based alternative splicing detection with additional filtering steps leading to more efficient statistical testing, and with detection of isoform-specific protein changes. A key methodological advance is reading frame prediction by translating exonic DNA in all possible frames, then finding a single open reading frame, or a single frame with matches to known proteins of the gene. This allowed unambiguous translation in 93.9% of alternative splicing events when tested on RNA-sequencing data of B cells from Sjögren’s syndrome patients. RiboSplitter does not depend on reference annotations and translates events even when one or both isoform(s) are novel (unannotated). RiboSplitter’s visualizations illustrate each event with translation outcomes, show event location within the gene, and align exons to protein domains. Nature Publishing Group UK 2023-11-15 /pmc/articles/PMC10651857/ /pubmed/37968320 http://dx.doi.org/10.1038/s41598-023-47348-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Najjar, Rayan
Mustelin, Tomas
Prediction of alternative pre-mRNA splicing outcomes
title Prediction of alternative pre-mRNA splicing outcomes
title_full Prediction of alternative pre-mRNA splicing outcomes
title_fullStr Prediction of alternative pre-mRNA splicing outcomes
title_full_unstemmed Prediction of alternative pre-mRNA splicing outcomes
title_short Prediction of alternative pre-mRNA splicing outcomes
title_sort prediction of alternative pre-mrna splicing outcomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651857/
https://www.ncbi.nlm.nih.gov/pubmed/37968320
http://dx.doi.org/10.1038/s41598-023-47348-6
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