Bioinformatics Advance Access originally published online on March 25, 2004
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Bioinformatics 20(12) © Oxford University Press 2004; all rights reserved.
A comparison of cluster analysis methods using DNA methylation data
1 Department of Preventive Medicine, 2 Department of Surgery and 3 Department of Biochemistry and Molecular Biology, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Received on July 15, 2003; revised on March 1, 2004; accepted on March 2, 2004
Advance Access Publication March 25, 2004
Motivation: Aberrant DNA methylation is common in cancer. DNA methylation profiles differ between tumor types and subtypes and provide a powerful diagnostic tool for identifying clusters of samples and/or genes. DNA methylation data obtained with the quantitative, highly sensitive MethyLight technology is not normally distributed; it frequently contains an excess of zeros. Established tools to analyze this type of data do not exist. Here, we evaluate a variety of methods for cluster analysis to determine which is most reliable.
Results: We introduce a Bernoulli–lognormal mixture model for clustering DNA methylation data obtained using MethyLight. We model the outcomes using a two-part distribution having discrete and continuous components. It is compared with standard cluster analysis approaches for continuous data and for discrete data. In a simulation study, we find that the two-part model has the lowest classification error rate for mixture outcome data compared with other approaches. The methods are illustrated using DNA methylation data from a study of lung cancer cell lines. Compared with competing hierarchical clustering methods, the mixture model approaches have the lowest cross-validation error for detecting lung cancer subtype (non-small versus small cell). The Bernoulli–lognormal mixture assigns observations to subgroups with the lowest uncertainty.
Availability: Software is available upon request from the authors.
Supplementary information: http://www-rcf.usc.edu/~kims/SupplementaryInfo.html
Contact: kims{at}usc.edu
* To whom correspondence should be addressed.
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