Bioinformatics Advance Access published online on August 4, 2005
Bioinformatics, doi:10.1093/bioinformatics/bti592
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1 Department of Biostatistics and Applied Mathematics, University of Texas M.D. Anderson Cancer Center 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 particular challenge is to detect genes with expression levels that change according to dose levels in a nonrandom 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 to 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 (5-FU). 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.
Received February 7, 2005
Revised May 22, 2005
Accepted July 18, 2005
Article
Analysis of dose-response effects on gene expression data with comparison of two microarray platforms
2 Department of Cancer Genetics, University of Texas M.D. Anderson Cancer Center 77030, USA
3 Department of Pathology, University of Texas M.D. Anderson Cancer Center 77030, USA
Kevin R. Coombes, E-mail: kcoombes{at}mdanderson.org
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