Can we build biological signatures for toxicity endpoints of interest to allow us to predict the chemical toxicity using genomic expression?
◦ Find other compounds with similar toxicity mechanism
◦ Use time series data (gene expression response response at different time points) to support hypotheses/draw conclusions
◦ Find compounds with apparently different genomic response at different time points, and use this to construct explanatory models
How reliable are genomic data as an alternative approach for animal toxicity testing?
• Compare expression of the known toxicants across different timepoints and databases.
• Compare pathways hypothesized based on gene expressions with other compounds of similar phenotypic toxicity.
Data to be used in case studies
ToxCast and Tox21 High-Throughput Screening Data: Over 8000 chemical substances screened against over 800 in vitro assay targets to identify potential toxicity endpoints.
ToxRefDB: in vivo animal toxicity and pathology data from US EPA guideline studies.
Open TG-GATEs: Open Toxicogenomics Project-Genomics Assisted Toxicity Evaluation system (Open TG-GATEs) is a toxicogenomics database open to the public for researchers to utilize research results of the Toxicogenomics Project (TGP) and the Toxicogenomics and Informatics Project (TGP2), and releases the data of 170 compounds analysed in the original TG-GATEs project. In Open TG-GATEs, it is possible to search toxicogenomics data by compound name or pathological finding. It is also possible to download gene expression data associated with phenotypic data such as pathological findings as a CEL file.