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Coding potential of the products of alternative splicing in human

Guido Leoni12, Loredana Le Pera1, Fabrizio Ferrè1, Domenico Raimondo1 and Anna Tramontano13*

Author Affiliations

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

2 INRAN, Via Ardeatina, 546 - 00178 Roma, Italy

3 Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza Università di Roma, P.le A. Moro, 5 - 00185 Rome, Italy

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Genome Biology 2011, 12:R9  doi:10.1186/gb-2011-12-1-r9

Published: 20 January 2011

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.