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20190917 - Status and Prospect of the Virtual Embryo Program (ETS)
Knudsen, T. 20190917 - Status and Prospect of the Virtual Embryo Program (ETS). European Teratology Society 47th annual meeting, Cologne, N/A, GERMANY, September 17 - 20, 2019. https://doi.org/10.23645/epacomptox.9922475
Presentation to the European Teratology Society 47th annual meeting in Sep 2019 for the symposium topic “Digitalisation meets Pathology and Developmental Toxicology”. This presentation will outline progress and challenges for a functional virtual embryo to model teratogenesis at the single-cell level.
Morphogenesis is mediated by coordinated action of cells interacting with one another and their micro-environment through systems of genetic signals and responses that are potentially vulnerable to chemical disruption. Computer models that integrate high-dimensional data on chemical-biological interactions (eg, ToxCast/Tox21) with the best available knowledge of embryology provide new ways to understand and predict developmental toxicity. Computational agent-based models (ABMs) have surfaced as a core technology for this purpose, here conceptualized in a ‘virtual embryo’ possessing artificial intelligence to recapitulate developmental processes and toxicities in silico. Using the CompuCell3D.org modeling environment, we have begun to build and test an array of simulations that self-organize into a morphogenetic series of events. These models self-assemble tissue-level phenomena (eg, biomechanics, epithelial-mesenchymal transition, morphogenetic fusion, contractility, convergent extension, folding, …) from fundamental cellular behaviors (eg, growth, apoptosis, differentiation, cell adhesion and motility, extracellular matrix synthesis) controlled by innate signaling gradients. They can be used to convey specific lesions from ToxCast/Tox21 in vitro data into critical phenomena underlying birth defects such as cleft palate or hypospadias. This presentation will outline progress and challenges for a functional virtual embryo to model teratogenesis at the single-cell level. This abstract does not reflect USEPA policy.
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