A New Approach in Applying Systems Engineering Tools and Analysis to Determine Hepatocyte Toxicogenomics Risk Levels to Human Health

摘要

Abstract There is an increasing backlog of potentially toxic compounds that cannot be evaluated with current animal-based approaches in a cost-effective and expeditious manner, thus putting human health at risk. Extrapolation of animal-based test results for human risk assessment often leads to different physiological outcomes. This article introduces the use of quantitative tools and methods from systems engineering to evaluate the risk of toxic compounds by the analysis of the amount of stress that human hepatocytes undergo in vitro when metabolizing GW76471 over extended times and concentrations. Hepatocytes are exceedingly connected systems that make it challenging to understand the highly varied dimensional genomics data to determine risk of exposure. Gene expression data of peroxisome proliferator-activated receptor-α (PPARα)2 binding was measured over multiple concentrations and varied times of GW7647 exposure and leveraging mahalanombis distance to establish toxicity threshold risk levels. The app..." /> rel="meta" type="application/atom+xml" href="http://dx.doi.org/10.1089%2Fcmb.2016.0073" /> rel="meta" type="application/rdf+json" href="http://dx.doi.org/10.1089%2Fcmb.2016.0073" /> rel="meta" type="application/unixref+xml" href="http://dx.doi.org/10.1089%2Fcmb.2016.0073" /> 展开▼