Skip Navigation



Bioinformatics Advance Access published online on January 18, 2008
Bioinformatics, doi:10.1093/bioinformatics/btm628
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
24/4/537    most recent
btm628v1
Right arrow Comments: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Comments are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Goeman, J. J.
Right arrow Articles by Mansmann, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goeman, J. J.
Right arrow Articles by Mansmann, U.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 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.

Multiple testing on the directed acyclic graph of gene ontology

Jelle J. Goeman 1,* and Ulrich Mansmann 2

1Dept. of Medical Statistics, Postzone S5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands
2IBE, Medical School, University of Munich and Department of Statistics, University of Munich

*To whom correspondence should be addressed. Dr. Jelle J. Goeman, E-mail: j.j.goeman{at}lumc.nl


  Abstract

Motivation: Current methods for multiplicity adjustment do not make use of the graph structure of Gene Ontology when testing for association of expression profiles of GO terms with a response variable.

Results: We propose a multiple testing method, called the focus level procedure, that preserves the graph structure of Gene Ontology (GO). The procedure is constructed as a combination of a Closed Testing procedure with Holm's method. It requires a user to choose a "focus level" in the GO graph, which reflects the level of specificity of terms in which the user is most interested. This choice also determines the level in the GO graph at which the procedure has most power. We prove that the procedure strongly controls the family-wise error rate without any additional assumptions on the joint distribution of the test statistics used. We also present an algorithm to calculate multiplicityadjusted p-values. Because the focus level procedure preserves the structure of the GO graph, it does not generally preserve the ordering of the raw p-values in the adjusted p-values.

Availability: The focus level procedure has been implemented in the globaltest and GlobalAncova packages, both of which are available on www.bioconductor.org.

Contact: j.j.goeman{at}lumc.nl

Associate Editor: Prof. David Rocke

Received on July 26, 2007; revised on November 28, 2007; accepted on December 16, 2007

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 BioinformaticsHome page
P. Du, G. Feng, J. Flatow, J. Song, M. Holko, W. A. Kibbe, and S. M. Lin
From disease ontology to disease-ontology lite: statistical methods to adapt a general-purpose ontology for the test of gene-ontology associations
Bioinformatics, June 15, 2009; 25(12): i63 - i68.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
C.-A. Tsai and J. J. Chen
Multivariate analysis of variance test for gene set analysis
Bioinformatics, April 1, 2009; 25(7): 897 - 903.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.