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Bioinformatics Advance Access originally published online on May 31, 2007
Bioinformatics 2007 23(15):1945-1951; doi:10.1093/bioinformatics/btm287
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Logistic regression for disease classification using microarray data: model selection in a large p and small n case

J.G. Liao 1,* and Khew-Voon Chin 2

1Drexel University School of Public Health, Philadelphia, PA 19102 and 2The University of Toledo,Toledo, OH 43614, USA

*To whom correspondence should be addressed.


  Abstract

Motivation: Logistic regression is a standard method for building prediction models for a binary outcome and has been extended for disease classification with microarray data by many authors. A feature (gene) selection step, however, must be added to penalized logistic modeling due to a large number of genes and a small number of subjects. Model selection for this two-step approach requires new statistical tools because prediction error estimation ignoring the feature selection step can be severely downward biased. Generic methods such as cross-validation and non-parametric bootstrap can be very ineffective due to the big variability in the prediction error estimate.

Results: We propose a parametric bootstrap model for more accurate estimation of the prediction error that is tailored to the microarray data by borrowing from the extensive research in identifying differentially expressed genes, especially the local false discovery rate. The proposed method provides guidance on the two critical issues in model selection: the number of genes to include in the model and the optimal shrinkage for the penalized logistic regression. We show that selecting more than 20 genes usually helps little in further reducing the prediction error. Application to Golub's leukemia data and our own cervical cancer data leads to highly accurate prediction models.

Availability: R library GeneLogit at http://geocities.com/jg_liao

Contact: jl544{at}drexel.edu

Associate Editor: Trey Ideker

Received on September 10, 2006; revised on May 14, 2007; accepted on May 21, 2007

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