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Biostatistics Advance Access published online on June 14, 2007
Biostatistics, doi:10.1093/biostatistics/kxm017
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Microarray learning with ABC

Dhammika Amaratunga*

Johnson & Johnson Pharmaceutical Research & Development LLC, Raritan, NJ 08869-0602, USA damaratu{at}prdus.jnj.com

Javier Cabrera and Vladimir Kovtun

Department of Statistics, Rutgers University, Piscataway, NJ 08854, USA

* To whom correspondence should be addressed.

Standard clustering algorithms when applied to DNA microarray data often tend to produce erroneous clusters. A major contributor to this divergence is the feature characteristic of microarray data sets that the number of predictors (genes) in such data far exceeds the number of samples by many orders of magnitude, with only a small percentage of predictors being truly informative with regards to the clustering while the rest merely add noise. An additional complication is that the predictors exhibit an unknown complex correlational configuration embedded in a small subspace of the entire predictor space. Under these conditions, standard clustering algorithms fail to find the true clusters even when applied in tandem with some sort of gene filtering or dimension reduction to reduce the number of predictors. We propose, as an alternative, a novel method for unsupervised classification of DNA microarray data. The method, which is based on the idea of aggregating results obtained from an ensemble of randomly resampled data (where both samples and genes are resampled), introduces a way of tilting the procedure so that the ensemble includes minimal representation from less important areas of the gene predictor space. The method produces a measure of dissimilarity between each pair of samples that can be used in conjunction with (a) a method like Ward's procedure to generate a cluster analysis and (b) multidimensional scaling to generate useful visualizations of the data. We call the dissimilarity measures ABC dissimilarities since they are obtained by aggregating bundles of clusters. An extensive comparison of several clustering methods using actual DNA microarray data convincingly demonstrates that classification using ABC dissimilarities offers significantly superior performance.

Keywords: Classification; Clustering; Random forest; Weighted random sampling

Received December 18, 2006; revised April 5, 2007; accepted for publication April 11, 2007.


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