Journal
BIOINFORMATICS
Volume 26, Issue 2, Pages 268-269Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/btp643
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Funding
- National Institutes of Health [R01-HG004634, R01-GM088809, R01-CA093769]
- Edward Mallinckrodt, Jr. Foundation
- University of Iowa Institute for Clinical and Translational Science (NIH) [UL1 RR024979]
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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).
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