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Integrative Modeling and AOP-based Simulation of Developmental Toxicity
Citation:
Knudsen, T. Integrative Modeling and AOP-based Simulation of Developmental Toxicity. Presented at European Societies of Toxicology (EuroTox), Brussels, N/A, BELGIUM, September 02 - 05, 2018. https://doi.org/10.23645/epacomptox.7098329
Impact/Purpose:
Presentation at Eurotox Sep 2018. The in silico reconstruction of tissue dynamics from the bottom-up, cell-by-cell and interaction-by-interaction, can return a probabilistic rendering of where, when and how a developmental defect might emerge.
Description:
Integrated Approaches to Testing and Assessment (IATA) can help focus DART resources by strategically targeting the most probable developmental hazards predicted by alternative in vitro assays and non-testing in silico platforms. Advances in biomedical engineering and computational sciences now enable high-throughput screening (HTS) to profile large chemical libraries for bioactivity. EPA’s ToxCast program has provided HTS data on thousands of chemicals and hundreds of in vitro assays that include biochemical assays, reporter cell lines, zebrafish developmental toxicity and stem cell platforms. Integration of HTS data with toxicokinetics (HTK), chemical structure-activity relationships (SAR), human cell-based organotypic culture models (OCM), adverse outcome pathways (AOPs), and multicellular agent-based models (ABM) offers a heuristic approach to an IATA for DART. Computational biology is uniquely position to translate this information predictively (bioactivity to apical outcome) and mechanistically (apical outcome to bioactivity) in a ‘virtual embryo’ that recapitulates the spatial and temporal diversity of morphological development. The in silico reconstruction of tissue dynamics from the bottom-up, cell-by-cell and interaction-by-interaction, can return a probabilistic rendering of where, when and how a developmental defect might emerge. This abstract does not reflect US EPA policy.
URLs/Downloads:
DOI: Integrative Modeling and AOP-based Simulation of Developmental Toxicity
EUROTOX_IATA_2018_V2_M.PDF (PDF, NA pp, 4948.105 KB, about PDF)