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Bioinformatics Advance Access originally published online on November 17, 2009
Bioinformatics 2010 26(2):268-269; doi:10.1093/bioinformatics/btp643
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

MADS+: discovery of differential splicing events from Affymetrix exon junction array data

Shihao Shen 1, Claude C. Warzecha 2, Russ P. Carstens 2,3 and Yi Xing 1,4,5,*

1 Department of Biostatistics, University of Iowa, Iowa City, IA, 2 Cell and Molecular Biology Graduate Group, 3 Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, 4 Department of Internal Medicine and 5 Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA

* To whom correspondence should be addressed.


  Abstract

Motivation: The Affymetrix Human Exon Junction Array is a newly designed high-density exon-sensitive microarray for global analysis of alternative splicing. Contrary to the Affymetrix exon 1.0 array, which only contains four probes per exon and no probes for exon–exon junctions, this new junction array averages eight probes per probeset targeting all exons and exon–exon junctions observed in the human mRNA/EST transcripts, representing a significant increase in the probe density for alternative splicing events. Here, we present MADS+, a computational pipeline to detect differential splicing events from the Affymetrix exon junction array data. For each alternative splicing event, MADS+ evaluates the signals of probes targeting competing transcript isoforms to identify exons or splice sites with different levels of transcript inclusion between two sample groups. MADS+ is used routinely in our analysis of Affymetrix exon junction arrays and has a high accuracy in detecting differential splicing events. For example, in a study of the novel epithelial-specific splicing regulator ESRP1, MADS+ detects hundreds of exons whose inclusion levels are dependent on ESRP1, with a RT-PCR validation rate of 88.5% (153 validated out of 173 tested).

Availability: MADS+ scripts, documentations and annotation files are available at http://www.medicine.uiowa.edu/Labs/Xing/MADSplus/.

Contact: yi-xing{at}uiowa.edu

Associate Editor: Trey Ideker

Received on August 29, 2009; revised on October 20, 2009; accepted on November 10, 2009

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