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Multiscale modeling and simulation of embryogenesis for in silico predictive toxicology (WC9)
Knudsen, T. Multiscale modeling and simulation of embryogenesis for in silico predictive toxicology (WC9). Presented at 9th World Congress on Alternatives and Animal use in the Life Sciences, Prague, CZECH REPUBLIC, August 24 - 28, 2014. https://doi.org/10.23645/epacomptox.5080204
Conference title: 9th World Congress on Alternatives and Animal use in the Life Sciences; Theme I – New Technologies, Session I-1 ‘Virtual Tissue Models’
Translating big data from alternative and HTS platforms into hazard identification and risk assessment is an important need for predictive toxicology and for elucidating adverse outcome pathways (AOPs) in developmental toxicity. Understanding how chemical disruption of molecular and cellular function in the human embryo propagates to higher levels of biological organization ultimately requires systems biology and computer simulation to synthesize and recapitulate spatio-temporal dynamics. Virtual Tissue Models (VTMs) can provide this level of detail for discrete morphogenetic events, based on simulating the connectivity between different scales of biological organization with cellular agent-based models (ABMs). The efficacy of VTMs to integrate empirical data with embryological information on an anatomical plane is being explored as a platform to evaluate chemical effects on a variety of systems. Progress will be reviewed for cardiovascular development (angiodysplasia), palatal fusion (cleft palate), limb outgrowth (ectrodactyly) and urethral development (hypospadias) among other systems just getting underway (thyrotropic neurodevelopment). Computer simulation with VTMs can offer a novel problem-solving environment that extends a traditional probabilistic paradigm (e.g., data to models in which ‘A’ will have a value y with probability p and uncertainty u) into a more granular environment based on lifestage-specific, spatio-temporal prediction of toxicological risk (e.g., what happens to system performance if a chemical exposure impacts protein ‘A’ and pathway ‘B’ at lifestage ‘C’ in the context of an AOP). This work was funded by the US EPA under its Chemical Safety for Sustainability Research Program but does not reflect US EPA policy.