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  RASE: recognition of alternatively spliced exons in C.elegans

Rätsch, G., Sonnenburg, S., & Schölkopf, B. (2005). RASE: recognition of alternatively spliced exons in C.elegans. Bioinformatics, 21(Supplement 1), i369-i377.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-D555-B Version Permalink: http://hdl.handle.net/21.11116/0000-0005-38CF-4
Genre: Conference Paper

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 Creators:
Rätsch, G1, Author              
Sonnenburg, S, Author              
Schölkopf, B2, 3, Author              
Affiliations:
1Friedrich Miescher Laboratory, Max Planck Society, Max-Planck-Ring 9, 72076 Tübingen, DE, ou_2575692              
2Department Empirical Inference, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497795              
3Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497794              

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 Abstract: Motivation: Eukaryotic pre-mRNAs are spliced to form mature mRNA. Pre-mRNA alternative splicing greatly increases the complexity of gene expression. Estimates show that more than half of the human genes and at least one-third of the genes of less complex organisms, such as nematodes or flies, are alternatively spliced. In this work, we consider one major form of alternative splicing, namely the exclusion of exons from the transcript. It has been shown that alternatively spliced exons have certain properties that distinguish them from constitutively spliced exons. Although most recent computational studies on alternative splicing apply only to exons which are conserved among two species, our method only uses information that is available to the splicing machinery, i.e. the DNA sequence itself. We employ advanced machine learning techniques in order to answer the following two questions: (1) Is a certain exon alternatively spliced? (2) How can we identify yet unidentified exons within known introns? Results: We designed a support vector machine (SVM) kernel well suited for the task of classifying sequences with motifs having positional preferences. In order to solve the task (1), we combine the kernel with additional local sequence information, such as lengths of the exon and the flanking introns. The resulting SVM-based classifier achieves a true positive rate of 48.5% at a false positive rate of 1%. By scanning over single EST confirmed exons we identified 215 potential alternatively spliced exons. For 10 randomly selected such exons we successfully performed biological verification experiments and confirmed three novel alternatively spliced exons. To answer question (2), we additionally used SVM-based predictions to recognize acceptor and donor splice sites. Combined with the above mentioned features we were able to identify 85.2% of skipped exons within known introns at a false positive rate of 1%.

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 Dates: 2005-06
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: DOI: 10.1093/bioinformatics/bti1053
BibTex Citekey: 3497
 Degree: -

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Title: Thirteenth International Conference on Intelligent Systems for Molecular Biology (ISBM 2005)
Place of Event: Detroit, MI, USA
Start-/End Date: 2005-06-25 - 2005-06-29

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Title: Bioinformatics
Source Genre: Journal
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Publ. Info: Oxford : Oxford University Press
Pages: - Volume / Issue: 21 (Supplement 1) Sequence Number: - Start / End Page: i369 - i377 Identifier: ISSN: 1367-4803
CoNE: https://pure.mpg.de/cone/journals/resource/954926969991