Bioinformatics Advance Access originally published online on April 29, 2004
Bioinformatics 2004 20(16):2579-2585; doi:10.1093/bioinformatics/bth288
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Bioinformatics vol. 20 issue 16 © Oxford University Press 2004; all rights reserved.
Genome wide identification and classification of alternative splicing based on EST data
1 Computational Molecular Biology Max Planck Institute for Molecular Genetics Ihnestrasse 73, D-14195 Berlin, Germany and 2 German Resource Center for Genome Research INF 580, 69120 Heidelberg, Germany
Received on October 10, 2003; revised on March 16, 2004; accepted on April 20, 2004
Advance Access Publication April 29, 2004
Motivation: Alternative splicing is currently seen to explain the vast disparity between the number of predicted genes in the human genome and the highly diverse proteome. The mapping of expressed sequences tag (EST) consensus sequences derived from the GeneNest database onto the genome provides an efficient way of predicting exon–intron boundaries, gene structure and alternative splicing events. However, the alternative splicing events are obscured by a large number of putatively artificial exon boundaries arising due to genomic contamination or alignment errors. The current work describes a methodology to associate quality values to the predicted exon–intron boundaries. High quality exon–intron boundaries are used to predict constitutive and alternative splicing ranked by confidence values, aiming to facilitate large-scale analysis of alternative splicing and splicing in general.
Results: Applying the current methodology, constitutive splicing is observed in 33 270 EST clusters, out of which 45% are alternatively spliced. The classification derived from the computed confidence values for 17 of these splice events frequently correlate (15/17) with RT–PCR experiments performed for 40 different tissue samples. As an application of the confidence measure, an evaluation of distribution of alternative splicing revealed that majority of variants correspond to the coding regions of the genes. However, still a significant fraction maps to non-coding regions, thereby indicating a functional relevance of alternative splicing in untranslated regions.
Availability: The predicted alternative splice variants are visualized in the SpliceNest database at http://splicenest.molgen.mpg.de
Supplementary information: For supplementary data, please refer Bioinformatics Online.
Contact: gupta{at}molgen.mpg.de
* To whom correspondence should be addressed.
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