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

Jianhua Hu·Mini Kapoor·Wei Zhang·Stanley R Hamilton·Kevin R Coombes
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Abstract

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@mdanderson.org

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AlgorithmsAntineoplastic AgentsCell Line, TumorColorectal NeoplasmsDose-Response Relationship, DrugFluorouracilGene Expression ProfilingGene Expression Regulation, NeoplasticHumansNeoplasm ProteinsOligonucleotide Array Sequence AnalysisTumor Cells, CulturedEvaluation StudyJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Jianhua Hu, Mini Kapoor, Wei Zhang, Stanley R Hamilton, Kevin R Coombes. 2005-08-04. Analysis of dose-response effects on gene expression data with comparison of two microarray platforms.. https://doi.org/10.1093/bioinformatics%2Fbti592

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