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Bioinformatics Advance Access originally published online on November 24, 2006
Bioinformatics 2007 23(3):306-313; doi:10.1093/bioinformatics/btl599
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© 2006 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.

Extensions to gene set enrichment

Zhen Jiang * and Robert Gentleman

Computational Biology, 1100 Fairview Avenue. N. M2-B876 PO Box 19024, Seattle, WA 98109-1024, USA

*To whom correspondence should be addressed.


  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.

Contact: zjiang{at}fhcrc.org

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Trey Ideker

Received on August 3, 2006; revised on October 24, 2006; accepted on November 21, 2006

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