Cluster stability scores for microarray data in cancer studies.docVIP

BMC Bioinformatics BioMedCentral Methodology article Open Access Cluster stability scores for microarray data in cancer studies Mark Smolkin1 and Debashis Ghosh*2 Address: 1Department of Health Evaluation Sciences, University of Virginia Medical Center, Charlottesville, Virginia, USA and 2Department of Biostatistics, University of Michigan Ann Arbor, Michigan, USA Email: Mark Smolkin - Marksmolkin@; Debashis Ghosh* - ghoshd@ * Corresponding author Published: 06 September 2003 Received: 28 April 2003 Accepted: 06 September 2003 BMC Bioinformatics 2003, 4:36 This article is available from: /1471-2105/4/36 ? 2003 Smolkin and Ghosh; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the articles original URL. Abstract Background: A potential benefit of profiling of tissue samples using microarrays is the generation of molecular fingerprints that will define subtypes of disease. Hierarchical clustering has been the primary analytical tool used to define disease subtypes from microarray experiments in cancer settings. Assessing cluster reliability poses a major complication in analyzing output from clustering procedures. While most work has focused on estimating the number of clusters in a dataset, the question of stability of individual-level clusters has not been addressed. Results: We address this problem by developing cluster stability scores using subsampling techniques. These scores exploit the redundancy in biologically discriminatory information on the chip. Our approach is generic and can be used with any clustering method. We propose procedures for calculating cluster stability scores for situations involving both known and unknown numbers of clusters. We also develop cluster-size adjusted stability scores. The method is illustrated by application to dat