Assessing conservation of alternative splicing with evolutionary splicing graphs
- 1Sorbonne Université, CNRS, IBPS, Laboratoire de Biologie Computationnelle et Quantitative (LCQB), 75005 Paris, France;
- 2Bioinformatics Unit (MF1), Department for Methods Development and Research Infrastructure, Robert Koch Institute, 13353 Berlin, Germany;
- 3Sorbonne Université, CNRS, LIP6, F-75005 Paris, France
Abstract
Understanding how protein function has evolved and diversified is of great importance for human genetics and medicine. Here, we tackle the problem of describing the whole transcript variability observed in several species by generalizing the definition of splicing graph. We provide a practical solution to construct parsimonious evolutionary splicing graphs where each node is a minimal transcript building block defined across species. We show a clear link between the functional relevance, tissue regulation, and conservation of alternative transcripts on a set of 50 genes. By scaling up to the whole human protein-coding genome, we identify a few thousand genes where alternative splicing modulates the number and composition of pseudorepeats. We have implemented our approach in ThorAxe, an efficient, versatile, robust, and freely available computational tool.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.274696.120.
- Received November 27, 2020.
- Accepted June 11, 2021.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
