Systems biology of liver toxicity predictions (SysBioToP)

Ronde 2014 Internationaal (Innovative Systems Toxicology for Alternatives to Animal Testing): There is a strong need to develop new toxicological approaches, incorporating mechanistic knowledge of toxicant action, using human cells as biological basis and leveraging the recent progress of systems biology. The SysBioToP project will address the exemplary question of liver toxicity by using this new strategy. The main question explored is whether high-throughput dynamic imaging data of cell stress responses can predict potential hepatotoxicity. For this purpose, imaging data sets from liver cells are connected by a systems biology model to toxic responses of the same cells. These two levels of information will be linked by mathematical equations and extensive data sets on toxicant-induced changes of gene transcription, cellular metabolism, and of the role of some of these genes in the stress response. The single cell information will be fed into a computer model of the three-dimensional liver structure. Thus, a network model predicting liver toxicity will be delivered.