The HeCaToS project (Hepatic and Cardiac Toxicity Systems modelling) aims at developing integrative in silico tools for predicting human liver and heart toxicity. The objective is to develop an integrated modeling framework, by combining advances in computational chemistry and systems toxicology, for modelling toxic perturbations in liver and heart across multiple scales.
This framework will include vertical integrations of representations from drug(metabolite)-target interactions, through macromolecules/proteins, to (sub-)cellular functionalities and organ physiologies, and even the human whole-body level.
In view of the importance of mitochondrial deregulations and of immunological dysfunctions associated with hepatic and cardiac drug-induced injuries, focus will be on these particular Adverse Outcome Pathways. Models will be populated with data from innovative in vitro 3D liver and heart assays challenged with prototypical hepato- or cardiotoxicants; data will be generated by advanced molecular and functional analytical techniques retrieving information on key (sub-)cellular toxic events.