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Bioinformatics Advance Access published online on January 19, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn017
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© The Author (2008). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Using repeated measurements to validate hierarchical gene clusters

Laurent Bréhélin a,*, Olivier Gascuel a and Olivier Martin c,b,*

Méthodes et Algorithmes pour la Bioinformatique, LIRMM, CNRS - Univ. Montpellier II, France
INRA, Unité protéomique, 2 Place Viala, 34060 Montpellier Cédex 1, France,INRA, Unité Biostatistique et Processus Spatiaux, 84914 Avignon Cédex 9, France

To whom correspondence should be addressed. Mr. Laurent Bréhélin, E-mail: brehelin{at}lirmm.fr


  Abstract

Motivation: Hierarchical clustering is a common approach to study protein and gene expression data. This unsupervised technique is used to find clusters of genes or proteins which are expressed in a coordinated manner across a set of conditions. Because of both the biological and technical variability, experimental repetitions are generally performed. In this work, we propose an approach to evaluate the stability of clusters derived from hierarchical clustering by taking repeated measurements into account.

Results: The method is based on the bootstrap technique that is used to obtain pseudo-hierarchies of genes from resampled datasets. Based on a fast dynamic programming algorithm, we compare the original hierarchy to the pseudo-hierarchies and assess the stability of the original gene clusters. Then a shuffling procedure can be used to assess the significance of the cluster stabilities. Our approach is illustrated on simulated data and on two microarray datasets. Compared to the standard hierarchical clustering methodology, it allows to point out the dubious and stable clusters, and thus avoids misleading interpretations.

Availability: The programs were developed in C and R languages.Supplementary Material and source code are available at address http://www.lirmm.fr/~brehelin/Stability/.

Contact: brehelin{at}lirmm.fr gascuel{at}lirmm.fr olivier.martin{at}avignon.inra.fr

Associate Editor: Dr. Trey Ideker

* Both authors contributed equally to this work

Received on October 2, 2007; revised on December 11, 2007; accepted on January 9, 2008

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