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Developmental Systems Toxicology: computer simulation in a ‘Virtual Embryo’ prototype (SEURAT-1 Progress Meeting)
Citation:
Knudsen, T. Developmental Systems Toxicology: computer simulation in a ‘Virtual Embryo’ prototype (SEURAT-1 Progress Meeting). SEURAT-1 Progress Meeting, Brussels, BELGIUM, December 04, 2015. https://doi.org/10.23645/epacomptox.5077654
Impact/Purpose:
This demo presentation will be presented as an active exhibit at the SEURAT-1 Symposium entitled "Painting the future animal-free safety assessment of chemical ingredients: Achievements of SEURAT-1".
Description:
Evaluating and assessing impacts to development is an Agency priority (EPA’s Children’s Environmental Health Research Roadmap); however, the quantity of chemicals needing assessment and challenges of species extrapolation require alternative approaches to traditional animal studies. One approach is to profile the human exposure universe of chemicals with HTS assays (in vitro) and then build computational (in silico) models that integrate these data with biological knowledge representing human development. Imputing HTS data into spatially-dynamic computer models of developmental signaling networks can then be used to simulate how an embryonic system might respond to a disturbance in the maternal environment. An in silico strategy with virtual tissue models can yield theoretical answers to relevant questions that are not attainable experimentally. This exhibition will demonstrate a workflow to build a cell agent-based computer model, seed it with HTS data, analyze cellular response networks and emergent properties, and compare simulations to adverse outcomes. This exploratory platform may be useful to evaluate chemical effects on development, such as disruption of cardiovascular development (angiodysplasia), palatal fusion (cleft palate), limb outgrowth (ectrodactyly) and urethral fusion (hypospadias) among other systems. Simulations of AOPs for embryonic disruption in a ‘Virtual Tissue Laboratory System’ can be built with biological information and parameterized with in vitro data for chemical prioritization and early lifestage exposure considerations. The views expressed in this presentation are those of the author and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency.
URLs/Downloads:
DOI: Developmental Systems Toxicology: computer simulation in a ‘Virtual Embryo’ prototype (SEURAT-1 Progress Meeting)
VEMBRYO_2015_SURAT_DEMO.PDF (PDF, NA pp, 3513.211 KB, about PDF)