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Bioinformatics Advance Access published online on July 2, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp406
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© The Author (2009). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Unite and conquer: univariate and multivariate approaches for finding differentially expressed gene sets

Galina V. Glazko 1,* and Frank Emmert-Streib 2

1Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642
2 Center for Cancer Research and Cell Biology School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK

*To whom correspondence should be addressed. Dr. Galina V. Glazko, E-mail: Galina_Glazko{at}urmc.rochester.edu


  Abstract

Motivation: Recently, many univariate and several multivariate approaches have been suggested for testing differential expression of gene sets between different phenotypes. However, despite a wealth of literature studying their performance on simulated and real biological data, still there is a need to quantify their relative performance when they are testing different null hypotheses.

Results: In this paper we compare the performance of univariate and multivariate tests on both simulated and biological data. In the simulation study we demonstrate that high correlations equally affect the power of both, univariate as well as multivariate tests. In addition, for most of them the power is similarly affected by the dimensionality of the gene set and by the percentage of genes in the set, for which expression is changing between two pheno-types. The application of different test statistics to biological data reveals that three statistics (sum of squared t-tests, Hotelling's T2, N-statistic), testing different null hypotheses, find some common but also some complementing differentially expressed gene sets under specific settings. This demonstrates that due to comple-menting null hypotheses each test projects on different aspects of the data and for the analysis of biological data it is beneficial to use all three tests simultaneously instead of focusing exclusively on just one.

Associate Editor: Dr. Joaquin Dopazo

Received on January 30, 2009; revised on April 2, 2009; accepted on June 29, 2009

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