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SOURCES OF VARIABILITY IN BASELINE GENE EXPRESSION IN RAT LIVER AND KIDNEY
Citation:
THOMPSON, K., M. BASS, M. BOEDIGHEIMER, P. BUSHEL, J. CHOU, C. CORTON, J. FOSTEL, F. LIU, AND R. WOLFINGER. SOURCES OF VARIABILITY IN BASELINE GENE EXPRESSION IN RAT LIVER AND KIDNEY. Presented at Society of Toxicology Annual Meeting 2007, Charlotte, NC, March 25 - 29, 2007.
Description:
Toxicogenomic studies are typically variable in design, but the impact of variations in study design and conduct on control animal gene expression has not been well characterized. A working group of the Health and Environmental Sciences Institute (HESI) Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment was formed to assess baseline gene expression variability from microarray data derived from control or vehicle-treated animals across multiple studies and sites. Eighteen sites voluntarily contributed a total of 536 Affymetrix data sets of rat liver and kidney samples from control animals. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics. Thirteen of these factors with complete data were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques as well as pattern analysis of the expression data. Certain factors emerged as key sources of variability, including gender, organ section, strain, and fasting, although a significant degree of confounding occurred due to the observational nature of the data and missing value patterns. The most variable and least variable probe sets within and between factors were identified and classified according to their gene ontology annotation. Better characterization of gene expression variability in control animals will aid in the design of toxicogenomic studies and in the interpretation of their results.