Systematic evaluation of isoform function in literature reports of alternative splicing

BMC Genomics
Shamsuddin A BhuiyanPaul Pavlidis

Abstract

Although most genes in mammalian genomes have multiple isoforms, an ongoing debate is whether these isoforms are all functional as well as the extent to which they increase the functional repertoire of the genome. To ground this debate in data, it would be helpful to have a corpus of experimentally-verified cases of genes which have functionally distinct splice isoforms (FDSIs). We established a curation framework for evaluating experimental evidence of FDSIs, and analyzed over 700 human and mouse genes, strongly biased towards genes that are prominent in the alternative splicing literature. Despite this bias, we found experimental evidence meeting the classical definition for functionally distinct isoforms for ~ 5% of the curated genes. If we relax our criteria for inclusion to include weaker forms of evidence, the fraction of genes with evidence of FDSIs remains low (~ 13%). We provide evidence that this picture will not change substantially with further curation and conclude there is a large gap between the presumed impact of splicing on gene function and the experimental evidence. Furthermore, many functionally distinct isoforms were not traceable to a specific isoform in Ensembl, a database that forms the basis for much co...Continue Reading

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Citations

Sep 24, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Klas HatjeMartin Kollmar
Aug 25, 2019·International Journal of Molecular Sciences·Rukeia El-AthmanAngela Relógio
Sep 22, 2020·RNA Biology·Mauno Vihinen
Oct 6, 2020·PLoS Computational Biology·Jose Manuel RodriguezMichael L Tress
May 5, 2021·Nature Genetics·Pavel V MazinHenrik Kaessmann
May 29, 2021·NAR Genomics and Bioinformatics·Fernando PozoMichael L Tress

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Methods Mentioned

BETA
gene knockouts
gene knockout

Software Mentioned

PULSE
APPRIS
PubMed utilities
Ensembl
RefSeq
BioMart
ClustalOmega

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