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Identification of Absorption, Distribution, Metabolism, and Excretion (ADME) Genes Relevant to Steatosis Using a Differential Gene Expression Approach
Citation:
Suarez, S. AND H. El-Masri. Identification of Absorption, Distribution, Metabolism, and Excretion (ADME) Genes Relevant to Steatosis Using a Differential Gene Expression Approach. SOT, New Orleans, LA, March 13 - 17, 2016.
Impact/Purpose:
This an abstract for a poster presentation in the upcoming Society of Toxicology Annual meeting March 2016.
Description:
Absorption, distribution, metabolism, and excretion (ADME) parameters represent important connections between exposure to chemicals and the activation of molecular initiating events of Adverse Outcome Pathways (AOPs) in cellular, tissue, and organ level targets. ADME parameters underly the mechanism by which chemical dose reaches the location where it can affect molecular targets. In order to better describe ADME parameters and how they can modulate potential hazard posed by chemical exposure, our goal is to create a database of ADME related genes and functional information. Given the scope of this task, we began using hepatic steatosis as a case study. To identify ADME genes related to steatosis, we have utilized the publicly available toxicogenomics database, DrugMatrixTM. This database contains standardized rodent chemical exposure data for over 2000 exposure conditions, along with differential gene expression data and corresponding associated pathological changes. We examined the entire chemical exposure microarray data set, including arrays gathered from chemical exposures resulting in pathologically confirmed cases of steatosis. From this differential gene expression data, we utilized differential and co-expression analyses to identify gene changes resulting from the chemical exposures leading to steatosis. We then utilized pathway enrichment analysis to further expand our gene set and identify differentially expressed genes (DEGs) related to ADME. These DEGs include multiple genes involved in the metabolism and clearance of chemical exposures, lipid metabolism and transport, and energy regulation. These results demonstrate the utility of a disease-focused case study as one method to populate our ADME gene database, thus increasing our understanding of the connection between exposure and AOPs.