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The Virtual Liver Project (v-Liver™):
A computational system for simulating chemical-induced injury in hepatic tissues

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Approach

There are three main components of the v-Liver™ Project. 

  1. A Liver Knowledgebase (KB) to describe the biological components, connections and the overall wiring diagram. This information is incomplete and dispersed across incompatible source. A semantic approach enables the intelligent organization of complex concepts that can be used to draw useful inferences. Representing tissue-level knowledge is organized across three main scales:
    1. Networks of molecular connections responsible for the fundamental activities of cells. Chemicals can interact with these networks and alter their topology or their dynamics
    2. Cells consisting of molecular networks, adapting to external stimuli such as nutrients, xenobiotics, or signals from other cells or organs
    3. The tissue as a network of parenchymal cells, connective tissue and vasculature, undergoing changes as the cells respond to stimuli. Injury is ultimately manifested at the tissue scale
  2. A simulation engine to analyse the independent/integrated behaviour of selected molecular, cellular and tissue level components. The goal of the simulator is to predict cellular changes emerging for the collective behaviour of liver cells, where each cell autonomously processes local information (nutrients, xenobiotics and signals) through molecular circuits.
  3. Novel experimental models to build, calibrate and evaluate the tissue model.

These strategic initiatives are aligned with the National Research Council’s report on "Toxicity Testing in the 21st Century: A Vision and a Strategy," which emphasizes the need for innovative approaches for testing toxicity of chemicals in humans.

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