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Bioinformatics Advance Access published online on February 24, 2006

Bioinformatics, doi:10.1093/bioinformatics/btl066
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© The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received October 19, 2005
Revised January 29, 2006
Accepted February 20, 2006

Article

Avoiding model selection bias in small-sample genomic data sets

Daniel Berrar 1 *, Ian Bradbury 1, and Werner Dubitzky 1

1 School of Biomedical Sciences, University of Ulster at Coleraine, Northern Ireland

* To whom correspondence should be addressed.
Daniel Berrar, E-mail: dp.berrar{at}ulster.ac.uk


   Abstract

Motivation: Genomic data sets generated by high-throughput technologies are typically characterized by a moderate number of samples and a large number of measurements per sample. As a consequence, classification models are commonly compared based on resampling techniques. This investigation discusses the conceptual difficulties involved in comparative classification studies. Conclusions derived from such studies are often optimistically biased, because the apparent differences in performance are usually not controlled in a statistically stringent framework taking into account the adopted sampling strategy. We investigate this problem by means of a comparison of various classifiers in the context of multiclass microarray data.

Results: Commonly used accuracy-based performance values, with or without confidence intervals, are inadequate for comparing classifiers for small-sample data. We present a statistical methodology that avoids bias in cross-validated model selection in the context of small-sample scenarios. This methodology is valid for both k-fold cross-validation and repeated random sampling.


Associate Editor: Joaquin Dopazo
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