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Genome Biol. 2011;12(1):R9. doi: 10.1186/gb-2011-12-1-r9. Epub 2011 Jan 20.

Coding potential of the products of alternative splicing in human.

Author information

  • 1Dipartimento di Scienze Biochimiche, Sapienza Università di Roma, P.le A. Moro, 5 - 00185 Rome, Italy.

Abstract

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.

PMID:
21251333
[PubMed - indexed for MEDLINE]
PMCID:
PMC3091307
Free PMC Article

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