WP7 Omics analyses

Description

The most challenging ‘omics technology to be incorporated into the  toxicogenomics approach in the near future, undoubtedly is next generation sequencing, which is capable of generating big data on molecular events induced by toxicants while simultaneously providing extensive information on yet unexplored responses such as alternative splicing.

Reporter assays with Green-Fluorescent-Protein or Luciferase constructs are interesting tools for high through put screening, and can be developed once a relevant mechanism specific target gene/protein is identified. However, because these will not provide global information at the systems biology level (such as whole genome effects, splice variants, transcription factors, etc.) they will not be applied within HeCaToS.

At the post-transcriptional expression and regulation level, proteomics has long lacked the capacity and accuracy to accurately analyse and describe large and complex systemsof proteins in signalling and functional networks. With the advent of latest generation separation (UPLC) and analytical techniques (high resolution, high speed, high accuracymass spectrometers) that can be used in combination with isotope label-based approachesand novel label-free bioinformatics approaches, proteomics today allow for the quantitative analysis of biological events at the proteome level including metabolic enzymes and key signalling molecules. While protein occurrence and abundance information is a central requirement for the development and refinement of systems oriented computational models, key information about enzyme activity and signalling activity is often not contained in this information but only revealed when investigating the phosphorylation modifications of the respective proteins.