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SOURCES OF VARIATION IN BASELINE GENE EXPRESSION LEVELS FROM TOXICOGENOMIC STUDY CONTROL ANIMALS ACROSS MULTIPLE LABORATORIES
Citation:
BOEDIGHEIMER, M. J., R. D. WOLFINGER, M. B. BASS, P. R. BUSHEL, J. W. CHOU, M. COOPER, C. CORTON, J. FOSTEL, S. D. HESTER, J. S. LEE, F. LIU, J. LIU, H. QIAN, J. QUACKENBUSH, S. PETTIT, AND K. L. THOMPSON. SOURCES OF VARIATION IN BASELINE GENE EXPRESSION LEVELS FROM TOXICOGENOMIC STUDY CONTROL ANIMALS ACROSS MULTIPLE LABORATORIES. BMC Genomics. BioMed Central Ltd, London, Uk, 9(285):2164-9, (2008).
Impact/Purpose:
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Description:
Variations in study design are typical for toxicogenomic studies, but their impact on gene expression in control animals has not been well characterized. A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 18 different sites. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. Certain factors emerged as key sources of variability, including gender, organ section, strain, and fasting state. Genes that are the most and least variable, gender-selective, or altered by fasting were also identified and functionally categorized. Better characterization of gene expression variability in control animals will aid in the design of toxicogenomic studies and in the interpretation of their results.