2020
DOI: 10.1101/2020.11.14.382820
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Assessing Conservation of Alternative Splicing with Evolutionary Splicing Graphs

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 generalising the definition of splicing graph. We provide a practical solution to building 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 c… Show more

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Cited by 3 publications
(4 citation statements)
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“…While orthologs usually maintain the ancestral function, paralogs are free to mutate and evolve new functions, as long as the ancestral role is preserved [12,13]. Remarkably, although multiple bioinformatic tools have been developed to identify homology relationships at the gene level [14][15][16][17][18], and some are emerging to investigate the conservation of splicing patterns [19], no corresponding tool currently exists to infer exon homologies, particularly over deep evolutionary timescales. Nonetheless, even in the absence of general-purpose tools, a variety of studies have underscored the importance of this approach.…”
Section: Introductionmentioning
confidence: 99%
“…While orthologs usually maintain the ancestral function, paralogs are free to mutate and evolve new functions, as long as the ancestral role is preserved [12,13]. Remarkably, although multiple bioinformatic tools have been developed to identify homology relationships at the gene level [14][15][16][17][18], and some are emerging to investigate the conservation of splicing patterns [19], no corresponding tool currently exists to infer exon homologies, particularly over deep evolutionary timescales. Nonetheless, even in the absence of general-purpose tools, a variety of studies have underscored the importance of this approach.…”
Section: Introductionmentioning
confidence: 99%
“…We estimate the evolutionary conservation of a s-exon (node) or a s-exon junction (edge) by quantifying the amount of species and transcripts including it, respectively. The heuristic for computing the ESG unfolds in five main steps (Zea et al, 2021): (1) cluster similar exons together, (2) define sub-exons within each species, (3) create a multiple sequence alignment (MSA) for each cluster, (4) identify s-exons as continuous blocks in the MSA, (5) refine s-exons. The TPF is a transcript-centred representation of the evolution of AS (Figure 1B).…”
Section: Definitions and Implementationmentioning
confidence: 99%
“…To this aim, we have recently developed a couple of efficient scalable computational methods. The first one, ThorAxe (Zea et al, 2021), adds an evolutionary dimension to the analysis of transcript variability by extending the notion of splicing graph to an ensemble of genes/species. It establishes a mapping between orthologous regions in a set of transcripts coming from different genes/species, and uses this mapping to decompose the transcripts into building blocks.…”
Section: Introductionmentioning
confidence: 99%
“…There is growing interest in how to approach transcripts in a phylogenetic context (Zea, et al 2021). Modes of splicing variation may differ across taxa (Clark and Thanaraj 2002;Kan, et al 2002;Ner-Gaon, et al 2004;Mei, et al 2017;Freese, et al 2019;Jia, et al 2020).…”
Section: Introductionmentioning
confidence: 99%