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Bioinformatics Advance Access published online on October 21, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp603
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© The Author (2009). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Accurate confidence aware clustering of array CGH tumor profiles

Bart P.P. van Houte and Jaap Heringa *

Centre for Integrative Bioinformatics VU (IBIVU), Faculty of Sciences and Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1081A, 1081 HV Amsterdam, The Netherlands

*To whom correspondence should be addressed. Dr. Jaap Heringa, E-mail: heringa{at}cs.vu.nl


  Abstract

Motivation: Chromosomal aberrations tend to be characteristic for given (sub) types of cancer. Such aberrations can be detected with array Comparative Genomic Hybridization (aCGH). Clustering aCGH tumor profiles aids in identifying chromosomal regions of interest and provides useful diagnostic information on the cancer type. An important issue here is to what extent individual aCGH tumor profiles can be reliably assigned to clusters associated with a given cancer type.

Results: We introduce a novel evolutionary fuzzy clustering (EFC) algorithm, which is able to deal with overlapping clusterings. Our method assesses these overlaps by using cluster membership degrees, which we use here as a confidence measure for individual samples to be assigned to a given tumor type. We first demonstrate the usefulness of our method using a synthetic aCGH dataset and subsequently show that EFC outperforms existing methods on four real datasets of aCGH tumor profiles involving four different cancer types. We also show that in general best performance is obtained using 1— Pearson correlation coefficient as a distance measure and that extra pre processing steps, such as segmentation and calling, lead to decreased clustering performance.

Availability: The source code of the program is available from http://ibi.vu.nl/programs/efcwww

Contact: heringa{at}few.vu.nl

Associate Editor: Prof. John Quackenbush

Received on April 28, 2009; accepted on October 16, 2009

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