MTSplice predicts effects of genetic variants on tissue-specific splicing

We develop the free and open-source model Multi-tissue Splicing (MTSplice) to predict the effects of genetic variants on splicing of cassette exons in 56 human tissues. MTSplice combines MMSplice, which models constitutive regulatory sequences, with a new neural network that models tissue-specific r...

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Autores principales: Cheng, Jun, Çelik, Muhammed Hasan, Kundaje, Anshul, Gagneur, Julien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Method
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011109/
https://www.ncbi.nlm.nih.gov/pubmed/33789710
http://dx.doi.org/10.1186/s13059-021-02273-7
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author Cheng, Jun
Çelik, Muhammed Hasan
Kundaje, Anshul
Gagneur, Julien
author_facet Cheng, Jun
Çelik, Muhammed Hasan
Kundaje, Anshul
Gagneur, Julien
author_sort Cheng, Jun
collection PubMed
description We develop the free and open-source model Multi-tissue Splicing (MTSplice) to predict the effects of genetic variants on splicing of cassette exons in 56 human tissues. MTSplice combines MMSplice, which models constitutive regulatory sequences, with a new neural network that models tissue-specific regulatory sequences. MTSplice outperforms MMSplice on predicting tissue-specific variations associated with genetic variants in most tissues of the GTEx dataset, with largest improvements on brain tissues. Furthermore, MTSplice predicts that autism-associated de novo mutations are enriched for variants affecting splicing specifically in the brain. We foresee that MTSplice will aid interpreting variants associated with tissue-specific disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s13059-021-02273-7).
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spelling pubmed-80111092021-03-31 MTSplice predicts effects of genetic variants on tissue-specific splicing Cheng, Jun Çelik, Muhammed Hasan Kundaje, Anshul Gagneur, Julien Genome Biol Method We develop the free and open-source model Multi-tissue Splicing (MTSplice) to predict the effects of genetic variants on splicing of cassette exons in 56 human tissues. MTSplice combines MMSplice, which models constitutive regulatory sequences, with a new neural network that models tissue-specific regulatory sequences. MTSplice outperforms MMSplice on predicting tissue-specific variations associated with genetic variants in most tissues of the GTEx dataset, with largest improvements on brain tissues. Furthermore, MTSplice predicts that autism-associated de novo mutations are enriched for variants affecting splicing specifically in the brain. We foresee that MTSplice will aid interpreting variants associated with tissue-specific disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s13059-021-02273-7). BioMed Central 2021-03-31 /pmc/articles/PMC8011109/ /pubmed/33789710 http://dx.doi.org/10.1186/s13059-021-02273-7 Text en © The Author(s) 2021 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Method
Cheng, Jun
Çelik, Muhammed Hasan
Kundaje, Anshul
Gagneur, Julien
MTSplice predicts effects of genetic variants on tissue-specific splicing
title MTSplice predicts effects of genetic variants on tissue-specific splicing
title_full MTSplice predicts effects of genetic variants on tissue-specific splicing
title_fullStr MTSplice predicts effects of genetic variants on tissue-specific splicing
title_full_unstemmed MTSplice predicts effects of genetic variants on tissue-specific splicing
title_short MTSplice predicts effects of genetic variants on tissue-specific splicing
title_sort mtsplice predicts effects of genetic variants on tissue-specific splicing
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011109/
https://www.ncbi.nlm.nih.gov/pubmed/33789710
http://dx.doi.org/10.1186/s13059-021-02273-7
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AT kundajeanshul mtsplicepredictseffectsofgeneticvariantsontissuespecificsplicing
AT gagneurjulien mtsplicepredictseffectsofgeneticvariantsontissuespecificsplicing

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