Journal Article

A flexible two-stage procedure for identifying gene sets that are differentially expressed

Ruth Heller, Elisabetta Manduchi, Gregory R. Grant and Warren J. Ewens

in Bioinformatics

Volume 25, issue 8, pages 1019-1025
Published in print April 2009 | ISSN: 1367-4803
Published online February 2009 | e-ISSN: 1460-2059 | DOI: http://dx.doi.org/10.1093/bioinformatics/btp076
A flexible two-stage procedure for identifying gene sets that are differentially expressed

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Motivation: Microarray data analysis has expanded from testing individual genes for differential expression to testing gene sets for differential expression. The tests at the gene set level may focus on multivariate expression changes or on the differential expression of at least one gene in the gene set. These tests may be powerful at detecting subtle changes in expression, but findings at the gene set level need to be examined further to understand whether they are informative and if so how.

Results: We propose to first test for differential expression at the gene set level but then proceed to test for differential expression of individual genes within discovered gene sets. We introduce the overall false discovery rate (OFDR) as an appropriate error rate to control when testing multiple gene sets and genes. We illustrate the advantage of this procedure over procedures that only test gene sets or individual genes.

Availability: R code (www.r-project.org) for implementing our approach is included as supplementary material.

Contact: ruheller@whatron.upenn.edu

Journal Article.  6377 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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