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Bioinformatics Advance Access published online on June 23, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn284
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

FIRMA: a method for detection of alternative splicing from exon array data

E. Purdom a,*, K.M. Simpson b, M.D. Robinson b,c, J.G. Conboy d, A.V. Lapuk d and T.P Speed a,b

aDepartment of Statistics, University of California at Berkeley, 367 Evans Hall #3860, Berkeley CA94720–3860, USA, bThe Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria, 3050, Australia, cDepartment of Medical Biology, University of Melbourne, Parkville, Victoria, 3010 Australia dLife Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley CA 94720, USA

*To whom correspondence should be addressed. Dr. Elizabeth Purdom, E-mail: epurdom{at}stat.berkeley.edu


  Abstract

Motivation: Analyses of EST data show that alternative splicing is much more widespread than once thought. The advent of exon and tiling microarrays means that researchers now have the capacity to experimentally measure alternative splicing on a genome–wide level. New methods are needed to analyze the data from these arrays.

Results: We present a method, FIRMA (Finding Isoforms using Robust Multichip Analysis), for detecting differential alternative splicing in exon array data. FIRMA has been developed for Affymetrix exon arrays, but could in principle be extended to other exon arrays, tiling arrays, or splice junction arrays. We have evaluated the method using simulated data, and have also applied it to two datasets: a panel of 11 human tissues and a set of 10 pairs of matched normal and tumor colon tissue. FIRMA is able to detect exons in several genes confirmed by reverse transcriptase PCR.

Availability: R code implementing our methods is contributed to the package aroma.affymetrix (Bengtsson et al., 2008).

Contact: epurdom{at}stat.berkeley.edu

Associate Editor: btn284

Received on February 25, 2008; revised on May 18, 2008; accepted on June 6, 2008

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