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The Virtual Liver Project (v-Liver™):
A computational system for simulating chemical-induced injury in hepatic tissues
v-Liver™ Navigation
Short-term (1-2 year) and long-term (3-5 year) goals
The 5-year plan for v-Liver™ is to develop a knowledgebase for qualitatively describing species-specific toxicity pathways due to exposure to chemicals, and to develop a virtual liver tissue that lays the foundation for quantitatively predicting the risk of non-genotoxic neoplastic lesions due to activation of certain genetic regulatory elements (ie, nuclear receptors and other transcription factors) in humans.
The short-term goals of the project are to: (a) curate mechanistic knowledge about non-genotoxic cancer in rodents and humans and to formally describe the species differences; (b) develop initial dynamic models of literature-derived NR-mediated molecular interaction networks, beginning with xenobiotic metabolism; and (c) develop an initial tissue level model of the hepatic lobule representing the key cell types, their interactions, and the nutrients and xenobiotic gradient due to blood flow.
The long-term goals are to: (a) extend the KB with additional molecular mechanisms; (b) expand the molecular interaction network to include additional key modules in relation to cell states; and (c) integrate the cell state model into the tissue model for multiscale simulation of injury. Once these goals area achieved the system will be extended to represent additional modes of action.