Application of Computational Systems Biology to Explore Environmental Toxicity Hazards

Karine Marie Laure Audouze, P. Grandjean

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


BACKGROUND: Computer-based modeling is part of a new approach to predictive toxicology. OBJECTIVES: We investigated the usefulness of an integrated computational systems biology approach in a case study involving the isomers and metabolites of the pesticide dichlorodiphenyltrichloroethane (DDT) to ascertain their possible links to relevant adverse effects. METHODS: We extracted chemical protein association networks for each DDT isomer and its metabolites using Chem Prot, a disease chemical biology database that includes both binding and gene expression data, and we explored protein protein interactions using a human interactome network. To identify associated dysfunctions and diseases, we integrated protein disease annotations into the protein complexes using the Online Mendelian Inheritance in Man database and the Comparative Toxicogenomics Database. RESULTS: We found 175 human proteins linked to p,p'-DDT, and 187 to o,p'-DDT. Dichlorodiphenyldichloroethylene (p,p'-DDE) was the metabolite with the highest number of links, with 52. We grouped proteins for each compound based on their disease annotations. Although the two data sources differed in linkage to diseases, integrated results predicted that most diseases were linked to the two DDT isomers. Asthma was uniquely linked with p,p'-DDT, and autism with o,p'-DDT. Several reproductive and neurobehavioral outcomes and cancer types were linked to all three compounds. CONCLUSIONS: Computer-based modeling relies on available information. Although differences in linkages to proteins may be due to incomplete data, our results appear meaningful and suggest that the parent DDT compounds may be responsible for more disease connections than the metabolites. The findings illustrate the potential use of computational approaches to toxicology.
TidsskriftEnvironmental Health Perspectives
Udgave nummer12
Sider (fra-til)1754-1759
Antal sider6
StatusUdgivet - 2011