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  Prediction of alternative isoforms from exon expression levels in RNA-Seq experiments

Richard, H., Schulz, M. H., Sultan, M., Nurnberger, A., Schrinner, S., Balzereit, D., et al. (2010). Prediction of alternative isoforms from exon expression levels in RNA-Seq experiments. Nucleic Acids Research, 38(10), e112-e112. doi:10.1093/nar/gkq041.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7AEF-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7AF0-2
Genre: Journal Article
Alternative Title : Nucleic Acids Res

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 Creators:
Richard, H.1, Author
Schulz, M. H.1, Author
Sultan, M.2, Author              
Nurnberger, A.3, Author              
Schrinner, S.2, Author              
Balzereit, D.2, Author              
Dagand, E.3, Author              
Rasche, A.4, Author              
Lehrach, H.3, Author              
Vingron, M.5, Author              
Haas, S. A.1, Author
Yaspo, M. L.2, Author              
Affiliations:
1Max Planck Society, ou_persistent13              
2Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479652              
3Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
4Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479648              
5Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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Free keywords: Alternative Splicing; Cell Line; Computer Simulation; Exons; Expressed Sequence Tags; Gene Expression Profiling; Humans; Models, Statistical; Oligonucleotide Array Sequence Analysis; Protein Isoforms/genetics/metabolism; Sequence Analysis, RNA
 Abstract: Alternative splicing, polyadenylation of pre-messenger RNA molecules and differential promoter usage can produce a variety of transcript isoforms whose respective expression levels are regulated in time and space, thus contributing specific biological functions. However, the repertoire of mammalian alternative transcripts and their regulation are still poorly understood. Second-generation sequencing is now opening unprecedented routes to address the analysis of entire transcriptomes. Here, we developed methods that allow the prediction and quantification of alternative isoforms derived solely from exon expression levels in RNA-Seq data. These are based on an explicit statistical model and enable the prediction of alternative isoforms within or between conditions using any known gene annotation, as well as the relative quantification of known transcript structures. Applying these methods to a human RNA-Seq dataset, we validated a significant fraction of the predictions by RT-PCR. Data further showed that these predictions correlated well with information originating from junction reads. A direct comparison with exon arrays indicated improved performances of RNA-Seq over microarrays in the prediction of skipped exons. Altogether, the set of methods presented here comprehensively addresses multiple aspects of alternative isoform analysis. The software is available as an open-source R-package called Solas at http://cmb.molgen.mpg.de/2ndGenerationSequencing/Solas/.

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Language(s): eng - English
 Dates: 2010-06
 Publication Status: Published in print
 Pages: -
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Title: Nucleic Acids Research
  Alternative Title : Nucleic Acids Res
Source Genre: Journal
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Pages: - Volume / Issue: 38 (10) Sequence Number: - Start / End Page: e112 - e112 Identifier: ISSN: 1362-4962 (Electronic) 0305-1048 (Linking) %R gkq041 [pii] 10.1093/nar/gkq041