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Nucleic Acids Research Advance Access published online on November 27, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl766
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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.

Methods Online

Absolute enrichment: gene set enrichment analysis for homeostatic systems

Vishal Saxena*, Dennis Orgill1 and Isaac Kohane2

Department of Surgery, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA 1 Surgery, Harvard Medical School Boston, Chief, Burns unit, Brigham and Women's Hosptial, Boston, MA, USA 2 Pediatrics and Health Sciences and Technology, Harvard Medical School Boston, Director, Children's Hospital Informatics Program, Boston, MA, USA

*To whom correspondence should be addressed. Tel: +1 6172302904; Fax: +1 6177326387; Email: vishal{at}mit.edu

Received April 18, 2006. Revised July 25, 2006. Accepted September 28, 2006.

The Gene Set Enrichment Analysis (GSEA) identifies sets of genes that are differentially regulated in one direction. Many homeostatic systems will include one limb that is upregulated in response to a downregulation of another limb and vice versa. Such patterns are poorly captured by the standard formulation of GSEA. We describe a technique to identify groups of genes (which sometimes can be pathways) that include both up- and down-regulated components. This approach lends insights into the feedback mechanisms that may operate, especially when integrated with protein interaction databases.


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