Coding potential of the products of alternative splicing in human.
KAUST Grant NumberKUK-I1-012-43
Permanent link to this recordhttp://hdl.handle.net/10754/596777
MetadataShow full item record
AbstractBACKGROUND: 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.
CitationLeoni G, Le Pera L, Ferrè F, Raimondo D, Tramontano A (2011) Coding potential of the products of alternative splicing in human. Genome Biology 12: R9. Available: http://dx.doi.org/10.1186/gb-2011-12-1-r9.
SponsorsThis work was supported by award number KUK-I1-012-43 made by King Abdullah University of Science and Technology (KAUST), by FIRB Italbionet and Proteomica and by Ministero della Salute Progetto RF-ID-2006-354931. The authors are grateful to Matteo Floris for useful discussions.
PubMed Central IDPMC3091307
CollectionsPublications Acknowledging KAUST Support
Except where otherwise noted, this item's license is described as This is an open access article distributed under the terms of the Creative Commons Attribution License (), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Comparative analysis indicates that alternative splicing in plants has a limited role in functional expansion of the proteome.
- Authors: Severing EI, van Dijk AD, Stiekema WJ, van Ham RC
- Issue date: 2009 Apr 9
- MAISTAS: a tool for automatic structural evaluation of alternative splicing products.
- Authors: Floris M, Raimondo D, Leoni G, Orsini M, Marcatili P, Tramontano A
- Issue date: 2011 Jun 15
- Alternative Splicing May Not Be the Key to Proteome Complexity.
- Authors: Tress ML, Abascal F, Valencia A
- Issue date: 2017 Feb
- Comparative proteomics reveals a significant bias toward alternative protein isoforms with conserved structure and function.
- Authors: Ezkurdia I, del Pozo A, Frankish A, Rodriguez JM, Harrow J, Ashman K, Valencia A, Tress ML
- Issue date: 2012 Sep
- Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human.
- Authors: Coutte L, Monté D, Imai K, Pouilly L, Dewitte F, Vidaud M, Adamski J, Baert JL, de Launoit Y
- Issue date: 1999 Nov 4