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Biostatistics Advance Access published online on December 22, 2007
Biostatistics, doi:10.1093/biostatistics/kxm048
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Weighted clustering of called array CGH data

Wessel N. Van Wieringen*

Department of Mathematics, Vrije Universiteit, De Boelelaan 1081a, 1081 HV Amsterdam, The Netherlands wvanwie{at}few.vu.nl

Mark A. Van De Wiel

Department of Mathematics, Vrije Universiteit, De Boelelaan 1081a, 1081 HV Amsterdam, The Netherlands, Department of Pathology, VU University Medical Center, PO Box 7075, 1007 MB Amsterdam, The Netherlands, and Department of Biostatistics, VU University Medical Center, PO Box 7075, 1007 MB Amsterdam, The Netherlands

Bauke Ylstra

Department of Pathology, VU University Medical Center, PO Box 7075, 1007 MB Amsterdam, The Netherlands

* To whom correspondence should be addressed.

Array comparative genomic hybridization (aCGH) is a laboratory technique to measure chromosomal copy number changes. A clear biological interpretation of the measurements is obtained by mapping these onto an ordinal scale with categories loss/normal/gain of a copy. The pattern of gains and losses harbors a level of tumor specificity. Here, we present WECCA (weighted clustering of called aCGH data), a method for weighted clustering of samples on the basis of the ordinal aCGH data. Two similarities to be used in the clustering and particularly suited for ordinal data are proposed, which are generalized to deal with weighted observations. In addition, a new form of linkage, especially suited for ordinal data, is introduced. In a simulation study, we show that the proposed cluster method is competitive to clustering using the continuous data. We illustrate WECCA using an application to a breast cancer data set, where WECCA finds a clustering that relates better with survival than the original one.

Keywords: Array CGH; Hierarchical clustering; Linkage; Ordinal data; Similarity; WECCA; Weighting

Received October 5, 2006; revised August 17, 2007; revised October 12, 2007; accepted for publication November 20, 2007.


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