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Bioinformatics Advance Access published online on November 24, 2006
Bioinformatics, doi:10.1093/bioinformatics/btl599
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© 2006 The Author(s)
Received August 3, 2006
Revised October 24, 2006
Accepted November 21, 2006

Article

Extensions to gene set enrichment

Zhen Jiang 1 * and Robert Gentleman 1

1 Computational Biology, 1100 Fairview Ave. N. M2-B876, P.O. Box 19024, Seattle, Washington 98109-1024

* To whom correspondence should be addressed.
Zhen Jiang, E-mail: zjiang{at}fhcrc.org


  Abstract

Motivation: Gene Set Enrichment Analysis (GSEA) has been developed recently to capture changes in the expression of pre-defined sets of genes. We propose number of extensions to GSEA, including the use of different statistics to describe the association between genes and phenotypes of interest. We make use of dimension reduction procedures, such as principle component analysis, to identify gene sets with correlated expression. We also address issues that arise when gene sets overlap.

Results: Our proposals extend the range of applicability of GSEA and allow for adjustments based on other covariates. We have provided a well defined procedure to address interpretation issues that can raise when gene sets have substantial overlap. We have shown how standard dimension reduction methods such as PCA, can be used to help further interpret GSEA.

Associate Editor: Trey Ideker
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