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IDENTIFICATION OF BIOLOGICALLY RELEVANT GENES USING A DATABASE OF RAT LIVER AND KIDNEY BASELINE GENE EXPRESSION
Citation:
CHOU, J., J. LIU, S. D. HESTER, J. S. LEE, K. THOMPSON, M. BASS, M. BOEDIGHEIMER, J. FOSTEL, F. LIU, R. WOLFINGER, P. BUSHEL, AND C. CORTON. IDENTIFICATION OF BIOLOGICALLY RELEVANT GENES USING A DATABASE OF RAT LIVER AND KIDNEY BASELINE GENE EXPRESSION. Presented at Society of Toxicology Annual Meeting 2007, Charlotte, NC, March 25 - 29, 2007.
Description:
Microarray data from independent labs and studies can be compared to potentially identify toxicologically and biologically relevant genes. The Baseline Animal Database working group of HESI was formed to assess baseline gene expression from microarray data derived from control or vehicle-treated rats across multiple studies and sites. We determined whether this database could be used to identify genes clearly associated with a number of biological factors that were part of the database. Eighteen sites contributed a total of 536 Affymetrix data sets of liver and kidney samples from control rats. We used Extracting Patterns and Identifying Genes (EPIG) to identify gender-specific and fasting-specific genes from each institute in which the factor could be examined in isolation. Gender-specific genes were identified in liver and kidney from a total of 5 different institutes using a total of 134 liver and 58 kidney transcript profiles. A total of 266 liver genes and 313 kidney genes were identified that exhibited similar behavior (both direction of change and degree of gender difference) in at least 2/4 and 2/3 institutes, respectively. Surprisingly, approximately 1/3 of the kidney genes were regulated in an opposite manner in liver. The gender genes overlapped with well-characterized genes from earlier studies. Using in silico approaches, we identified a number of known response elements in the promoters of co-regulated genes including those involved in determining gender-specific gene expression. Fasting-specific genes were also identified in a similar manner using a total of 89 profiles from 5 institutes. The genes significantly overlapped with those that were known to be regulated by fasting in rodents. Our results demonstrate that biologically relevant genes that are associated with a number of biological variables common to toxicology studies can be identified using a well annotated database of microarray data from multiple sources.