The Applied Systems Toxicology Approach

Applied systems toxicology refers to the ‘-omics-based evaluation of biological systems upon perturbation by chemical stressors, by monitoring molecular pathways and toxicological endpoints and iteratively integrating these response data to model the toxicological system. A key strength of applied systems toxicology is its emphasis on the integration of data from different studies and analytical platforms to produce a richer and biologically more refined understanding of the toxicological response of a cell, organ, or organism. It is expected that such integration of data will yield a more complete picture of the biology behind the pathway modulations that are associated with a particular toxicant treatment, shedding light not only on what the cell is planning (transcriptomics), but also on what occurs in the proteome and metabolome. Therefore, transcriptomics, proteomics, metabolomics, and high-throughput techniques are collectively used to collect quantitative data for the construction and validation of models, complemented by the use of high-level bioinformatics to integrate and holistically interpret these data.

NTC will develop and advance applied systems toxicology through a three-step research strategy:

  • Seek common denominators in toxic perturbations of the biological system in vitro by applying transcriptomics, proteomics, and metabolomics to identify central hubs in pathway responses which may represent the most reliable predictors of toxicity;
  • Validate in vitro assays for human hazard identification iv vivo, by interacting with clinical trials and pharmacotherapy, and by performing exploratory studies among human volunteers; 
  • Use a systems biology-based approach to develop and implement novel systems models for safety evaluation of chemicals.

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