SESSION 5: Transcriptomics hit the target
Medical University of Innsbruck
High content omic methods provide a deep insight into changes in mRNA levels upon chemical exposure.
However, this increased analytical precision is not yet matched by the extent of our understanding of molecular mechanisms to make an optimal interpretation of these biological changes.
For transcriptomics (TCX) performed by microarray or more recently RNA sequencing, a particular type of molecular effects can be assessed already: the modulation of the transcriptional activity of a transcription factor (TF).
ChIP-seq datasets reporting groups of genes specifically regulated by a TF are now publicly available for mining, allowing the generation of target gene lists of TFs of toxicological relevance, based on actual protein-DNA interaction and effective modulation of gene expression.
This talk will focus on the generation of target gene signatures for Nrf2, ATF4, HIF1a, AhR and PPAR gamma to monitor their modulation in large in vitro TCX datasets from renal and hepatic models exposed to clinical nephro- and hepato-toxins.
The result is a tool to monitor TF-driven stress responses and other toxicity pathways to inform on mechanisms of toxicity for chemical hazard identification.