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Mechanistic modeling of developmental defects through computational embryology (WC10th)
Citation:
Knudsen, T., S. Hunter, N. Baker, R. Spencer, J. Glazier, G. Daston, AND A. Piersma. Mechanistic modeling of developmental defects through computational embryology (WC10th). Presented at 10th World Congress on Alternatives and Animal Use in the Life Sciences, Seattle, WA, August 20 - 24, 2017.
Impact/Purpose:
Slide presentation at the 10th World Congress on Alternatives and Animal Use in the Life Sciences
Description:
Abstract: An important consideration for 3Rs is to identify developmental hazards utilizing mechanism-based in vitro assays (e.g., ToxCast) and in silico predictive models. Steady progress has been made with agent-based models that recapitulate morphogenetic drivers for angiogenesis, somitogenesis, urethrogenesis, and palatogenesis. Additional models are underway for the neurovascular unit, endocardial cushions, and neural tube closure. The models offer a heuristic approach to reconstruct tissue dynamics from the bottom-up, cell-by-cell and interaction-by-interaction. Individually, they can simulate emergent phenotypes and predict adverse outcomes or ‘cybermorphs’ to essentially bring an AOP to life utilizing computational dynamics. Collectively, their compilation into an integrated array or ‘virtual embryo’ motivates the construction of novel ontology systems to integrate molecular pathways, cellular behaviors, and in vitro data on chemical-biological interactions with extant knowledge of embryology. This abstract does not reflect US EPA policy.
URLs/Downloads:
WC10_VTLS_ABSTRACT_032817.PDF (PDF, NA pp, 104.792 KB, about PDF)KNUDSEN_ABM_WC10_M.PDF (PDF, NA pp, 2494.512 KB, about PDF)