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Coding potential of the products of alternative splicing in human

BACKGROUND: Analysis of the human genome has revealed that as much as an order of magnitude more of the genomic sequence is transcribed than accounted for by the predicted and characterized genes. A number of these transcripts are alternatively spliced forms of known protein coding genes; however, i...

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Autores principales: Leoni, Guido, Le Pera, Loredana, Ferrè, Fabrizio, Raimondo, Domenico, Tramontano, Anna
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091307/
https://www.ncbi.nlm.nih.gov/pubmed/21251333
http://dx.doi.org/10.1186/gb-2011-12-1-r9
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author Leoni, Guido
Le Pera, Loredana
Ferrè, Fabrizio
Raimondo, Domenico
Tramontano, Anna
author_facet Leoni, Guido
Le Pera, Loredana
Ferrè, Fabrizio
Raimondo, Domenico
Tramontano, Anna
author_sort Leoni, Guido
collection PubMed
description BACKGROUND: Analysis of the human genome has revealed that as much as an order of magnitude more of the genomic sequence is transcribed than accounted for by the predicted and characterized genes. A number of these transcripts are alternatively spliced forms of known protein coding genes; however, it is becoming clear that many of them do not necessarily correspond to a functional protein. RESULTS: In this study we analyze alternative splicing isoforms of human gene products that are unambiguously identified by mass spectrometry and compare their properties with those of isoforms of the same genes for which no peptide was found in publicly available mass spectrometry datasets. We analyze them in detail for the presence of uninterrupted functional domains, active sites as well as the plausibility of their predicted structure. We report how well each of these strategies and their combination can correctly identify translated isoforms and derive a lower limit for their specificity, that is, their ability to correctly identify non-translated products. CONCLUSIONS: The most effective strategy for correctly identifying translated products relies on the conservation of active sites, but it can only be applied to a small fraction of isoforms, while a reasonably high coverage, sensitivity and specificity can be achieved by analyzing the presence of non-truncated functional domains. Combining the latter with an assessment of the plausibility of the modeled structure of the isoform increases both coverage and specificity with a moderate cost in terms of sensitivity.
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spelling pubmed-30913072011-05-11 Coding potential of the products of alternative splicing in human Leoni, Guido Le Pera, Loredana Ferrè, Fabrizio Raimondo, Domenico Tramontano, Anna Genome Biol Research BACKGROUND: Analysis of the human genome has revealed that as much as an order of magnitude more of the genomic sequence is transcribed than accounted for by the predicted and characterized genes. A number of these transcripts are alternatively spliced forms of known protein coding genes; however, it is becoming clear that many of them do not necessarily correspond to a functional protein. RESULTS: In this study we analyze alternative splicing isoforms of human gene products that are unambiguously identified by mass spectrometry and compare their properties with those of isoforms of the same genes for which no peptide was found in publicly available mass spectrometry datasets. We analyze them in detail for the presence of uninterrupted functional domains, active sites as well as the plausibility of their predicted structure. We report how well each of these strategies and their combination can correctly identify translated isoforms and derive a lower limit for their specificity, that is, their ability to correctly identify non-translated products. CONCLUSIONS: The most effective strategy for correctly identifying translated products relies on the conservation of active sites, but it can only be applied to a small fraction of isoforms, while a reasonably high coverage, sensitivity and specificity can be achieved by analyzing the presence of non-truncated functional domains. Combining the latter with an assessment of the plausibility of the modeled structure of the isoform increases both coverage and specificity with a moderate cost in terms of sensitivity. BioMed Central 2011 2011-01-20 /pmc/articles/PMC3091307/ /pubmed/21251333 http://dx.doi.org/10.1186/gb-2011-12-1-r9 Text en Copyright ©2011 Leoni et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Leoni, Guido
Le Pera, Loredana
Ferrè, Fabrizio
Raimondo, Domenico
Tramontano, Anna
Coding potential of the products of alternative splicing in human
title Coding potential of the products of alternative splicing in human
title_full Coding potential of the products of alternative splicing in human
title_fullStr Coding potential of the products of alternative splicing in human
title_full_unstemmed Coding potential of the products of alternative splicing in human
title_short Coding potential of the products of alternative splicing in human
title_sort coding potential of the products of alternative splicing in human
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091307/
https://www.ncbi.nlm.nih.gov/pubmed/21251333
http://dx.doi.org/10.1186/gb-2011-12-1-r9
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