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Bioinformatics Advance Access originally published online on August 4, 2005
Bioinformatics 2005 21(17):3524-3529; doi:10.1093/bioinformatics/bti592
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions{at}oupjournals.org

Analysis of dose–response effects on gene expression data with comparison of two microarray platforms

Jianhua Hu 1, Mini Kapoor 2, Wei Zhang 3, Stanley R. Hamilton 3 and Kevin R. Coombes 1,*

1Department of Biostatistics and Applied Mathematics, University of Texas MD Anderson Cancer Center Houston, TX 77030, USA
2Department of Cancer Genetics, University of Texas MD Anderson Cancer Center Houston, TX 77030, USA
3Department of Pathology, University of Texas MD Anderson Cancer Center Houston, TX 77030, USA

*To whom correspondence should be addressed.

Motivation: The problems of analyzing dose effects on gene expression are gaining attention in biomedical research. A specific challenge is to detect genes with expression levels that change according to dose levels in a non-random manner, but nonetheless may be considered as potential biomarkers.

Method: We are among the first to formally apply a tool that uses an isotonic (monotonic) regression approach to this area of study. We introduce a test statistic to select genes with significant dose–response expression in a monotonic fashion based on a permutation procedure. We then compare the results with those achieved from the application of a likelihood ratio-based test.

Results: We apply the isotonic regression approach to a study of gene expression in the RKO colon carcinoma cell line in response to varying dosage levels of the chemotherapeutic agent 5-fluorouracil. A feature of both Affymetrix and printed 75mer oligomer cDNA arrays produced from the same samples provides an opportunity to compare the two microarray platforms.

Availability: Statistical software S-plus Code to implement the method is available from the authors.

Contact: kcoombes{at}mdanderson.org

Received on February 7, 2005; revised on May 22, 2005; accepted on July 18, 2005

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