S08: The challenge of integrating different “omics” technologies

“Omics” technologies like toxicogenomics, metabonomics and proteomics, offer new opportunities to investigate the effects of a chemical exposure as part of toxicology studies. However, none of these methods alone can provide the whole picture of a biological system. The PredTox (Predictive Toxicology) consortium focuses on the combined application of established toxicological endpoints and “omics” technologies to characterize hepato- and nephrotoxicants on the molecular level. Sixteen compounds were tested in rats at different sites using a harmonized experimental protocol. Classical toxicological parameters were monitored and additional samples (tissue, blood, urine) collected for toxicogenomics, proteomics and metabonomics. Protocols for “omics” technologies were standardized regarding technical aspects and quality control. Concomitantly, a database to house these highly interlinked data was created and implemented. The generated data are analyzed separately as well as within and across technologies and studies. First results indicate a site specific clustering for toxicogenomics and partly metabonomics. This effect could be overcome by normalization or application of correction algorithms. Integration of “omics” technologies is first applied within individual studies. Pathway analysis is expected to offer opportunities to compare changes on the gene, protein and metabolite level. Comparison across studies should lead to the generation of hypotheses to understand the underlying mechanisms of the observed toxicities as well as the identification of biological markers of hepato- or nephrotoxicity. In summary, only the integration of data from different biological levels will give a global insight into cellular behaviour. The development of methodologies for data integration constitutes a major research challenge within the PredTox Consortium.