Supporting data for "Map and Model – moving from observation to prediction in toxicogenomics"

Chemicals induce compound specific changes on the transcriptome of an organism (toxicogenomic finngerprints). This provides potential insights about the cellular or physiological responses to chemical exposure and adverse effects, which is needed in assessment of chemical related hazards or environmental health. In this regard, comparison or connection of dfferent experiments becomes important when interpreting toxicogenomic experiments. Due to lack of capturing response dynamics, comparability is often limited. In this study, we aim to overcome these constraints. <br>We developed an experimental design and bioinformatic analysis strategy to infer time and concentration-resolved toxicogenomic fingerprints. We projected the fingerprints to a universal coordinate system (toxicogenomic universe), based on a self-organizing map of toxicogenomic data retrieved from public databases. Genes clustering together in regions of the map indicate functional relation due to co-expression under chemical exposure. To allow for quantitative description and extrapolation of the gene-expression responses we developed a time and concentration-dependent regression model.<br> We applied the analysis strategy in a microarray case study exposing zebrafish embryos to three selected model compounds including two cyclooxygenase inhibitors. After identification of key responses in the transcriptome we could compare and characterise their association to developmental, toxicokinetic, and toxicodynamic processes using the parameter estimates for affected gene clusters. Furthermore, we discuss an association of toxicogenomic effects with measured internal concentrations. The design and analysis pipeline described here could serve as a blueprint for creating comparable toxicogenomic fingerprints of chemicals. It integrates, aggregates, and models time and concentration-resolved toxicogenomic data.