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ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences

BACKGROUND: Currently available methods to predict splice sites are mainly based on the independent and progressive alignment of transcript data (mostly ESTs) to the genomic sequence. Apart from often being computationally expensive, this approach is vulnerable to several problems – hence the need t...

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Detalles Bibliográficos
Autores principales: Bonizzoni, Paola, Rizzi, Raffaella, Pesole, Graziano
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1276783/
https://www.ncbi.nlm.nih.gov/pubmed/16207377
http://dx.doi.org/10.1186/1471-2105-6-244
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author Bonizzoni, Paola
Rizzi, Raffaella
Pesole, Graziano
author_facet Bonizzoni, Paola
Rizzi, Raffaella
Pesole, Graziano
author_sort Bonizzoni, Paola
collection PubMed
description BACKGROUND: Currently available methods to predict splice sites are mainly based on the independent and progressive alignment of transcript data (mostly ESTs) to the genomic sequence. Apart from often being computationally expensive, this approach is vulnerable to several problems – hence the need to develop novel strategies. RESULTS: We propose a method, based on a novel multiple genome-EST alignment algorithm, for the detection of splice sites. To avoid limitations of splice sites prediction (mainly, over-predictions) due to independent single EST alignments to the genomic sequence our approach performs a multiple alignment of transcript data to the genomic sequence based on the combined analysis of all available data. We recast the problem of predicting constitutive and alternative splicing as an optimization problem, where the optimal multiple transcript alignment minimizes the number of exons and hence of splice site observations. We have implemented a splice site predictor based on this algorithm in the software tool ASPIC (Alternative Splicing PredICtion). It is distinguished from other methods based on BLAST-like tools by the incorporation of entirely new ad hoc procedures for accurate and computationally efficient transcript alignment and adopts dynamic programming for the refinement of intron boundaries. ASPIC also provides the minimal set of non-mergeable transcript isoforms compatible with the detected splicing events. The ASPIC web resource is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility. CONCLUSION: Extensive bench marking shows that ASPIC outperforms other existing methods in the detection of novel splicing isoforms and in the minimization of over-predictions. ASPIC also requires a lower computation time for processing a single gene and an EST cluster. The ASPIC web resource is available at .
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spelling pubmed-12767832005-11-16 ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences Bonizzoni, Paola Rizzi, Raffaella Pesole, Graziano BMC Bioinformatics Software BACKGROUND: Currently available methods to predict splice sites are mainly based on the independent and progressive alignment of transcript data (mostly ESTs) to the genomic sequence. Apart from often being computationally expensive, this approach is vulnerable to several problems – hence the need to develop novel strategies. RESULTS: We propose a method, based on a novel multiple genome-EST alignment algorithm, for the detection of splice sites. To avoid limitations of splice sites prediction (mainly, over-predictions) due to independent single EST alignments to the genomic sequence our approach performs a multiple alignment of transcript data to the genomic sequence based on the combined analysis of all available data. We recast the problem of predicting constitutive and alternative splicing as an optimization problem, where the optimal multiple transcript alignment minimizes the number of exons and hence of splice site observations. We have implemented a splice site predictor based on this algorithm in the software tool ASPIC (Alternative Splicing PredICtion). It is distinguished from other methods based on BLAST-like tools by the incorporation of entirely new ad hoc procedures for accurate and computationally efficient transcript alignment and adopts dynamic programming for the refinement of intron boundaries. ASPIC also provides the minimal set of non-mergeable transcript isoforms compatible with the detected splicing events. The ASPIC web resource is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility. CONCLUSION: Extensive bench marking shows that ASPIC outperforms other existing methods in the detection of novel splicing isoforms and in the minimization of over-predictions. ASPIC also requires a lower computation time for processing a single gene and an EST cluster. The ASPIC web resource is available at . BioMed Central 2005-10-05 /pmc/articles/PMC1276783/ /pubmed/16207377 http://dx.doi.org/10.1186/1471-2105-6-244 Text en Copyright © 2005 Bonizzoni 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 Software
Bonizzoni, Paola
Rizzi, Raffaella
Pesole, Graziano
ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences
title ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences
title_full ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences
title_fullStr ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences
title_full_unstemmed ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences
title_short ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences
title_sort aspic: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences
topic Software
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1276783/
https://www.ncbi.nlm.nih.gov/pubmed/16207377
http://dx.doi.org/10.1186/1471-2105-6-244
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