Work package 3.2.2

Toxicogenomics is defined as the study of global changes of the abundances of biological molecules (transcripts, proteins, metabolites) caused by an external stimulus such as drug treatment. Modern high throughput assay technologies like metabonomics and proteomics and transcriptomics , in combination with conventional toxicology endpoints, contribute to a new systems toxicology approach.

Within the InnoMed PredTox project, the task of the toxicotranscriptomics work package is to analyze the changes on the gene expression profiles of several tissues after systemic exposure to the 16 test compounds selected in WP 3.1. With this purpose, tissue samples from liver and kidney, as well as blood from all animals, were collected for subsequent RNA extraction and microarray analysis.

The microarray analysis was performed on commercially available Genechips® from Affymetrix, representing all known sequences of the rat genome RAE 230 2.0. The assays were run based on a standardized protocol at several consortium member sites. Gene expression analysis in liver and kidney was performed essentially as suggested by Affymetrix. An additional step for globin reduction using Genelogic globin reduction oligonucleotides was included for the analysis of gene expression in blood. All the raw data were transferred to the central database hosted at Genedata. Statistics-based quality control of the raw data and standardized processing for further analyses were performed with Genedata Expressionist.