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Bioinformatics Advance Access published online on August 8, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm387
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© The Author (2007). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Query-driven module discovery in microarray data

Thomas Dhollander 1,*, Qizheng Sheng 1, Karen Lemmens 1, Bart De Moor 1, Kathleen Marchal 2 and Yves Moreau 1

1Department of Electrical Engineering ESAT-SCD, Katholieke Universiteit Leuven, Kasteelpark Arenberg 10, Leuven-Heverlee, 3001, Belgium, 2CMPG, Department of Microbial and Molecular Systems, K.U.Leuven, Kasteelpark Arenberg 20, B-3001 Leuven, Belgium

*To whom correspondence should be addressed. Thomas Dhollander, E-mail: Thomas.dhollander{at}esat.kuleuven.be


  Abstract

Motivation: Existing (bi)clustering methods for microarray data analysis often do not answer the specific questions of interest to a biologist. Such specific questions could be derived from other information sources, including expert prior knowledge. More specifically, given a set of seed genes which are believed to have a common function, we would like to recruit genes with similar expression profiles as the seed genes in a significant subset of experimental conditions.

Results: We introduce QDB, a novel Bayesian query-driven biclustering framework in which the prior distributions allow introducing knowledge from a set of seed genes (query) to guide the pattern search. In two well-known yeast compendia, we grow highly functionally enriched biclusters from small sets of seed genes using a resolution sweep approach. In addition, relevant conditions are identified and modularity of the biclusters is demonstrated, including the discovery of overlapping modules. Finally, our method deals with missing values naturally, performs well on artificial data from a recent biclustering benchmark study and has a number of conceptual advantages when compared to existing approaches for focused module search.

Availability: Software is available on the supplementary website.

Contact: Thomas.dhollander{at}esat.kuleuven.be

Supplementary Information: Available on http://homes.esat.kuleuven.be/~tdhollan/Supplementary_Information_Dhollander_2007/index.html

Associate Editor: Prof. John Quackenbush

Received on February 4, 2007; revised on July 12, 2007; accepted on July 22, 2007

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