Hepatotoxicity Prediction by Systems Biology Modeling of Disturbed Metabolic Pathways Using Gene Expression Data.

The present method describes a systems biology approach for the in silico predictive modeling of drug toxicity. The data from LINCS were used to determine the type and number of pathways disturbed by each compound and to estimate the extent of disturbance (network perturbation elasticity). Moreover, the most frequently disturbed metabolic pathways and reactions were determined across the studied toxicants. The process was exemplified by successful predictions on various statins. In conclusion, an entirely new approach linking gene expression alterations to the prediction of complex organ toxicity was developed.