Deciphering Diseases and Biological Targets for Environmental Chemicals using Toxicogenomics Networks

Karine Audouze, Agnieszka Sierakowska Juncker, Francisco J S S A Roque, Konrad Krysiak-Baltyn, Nils Weinhold, Olivier Taboureau, Thomas Skøt Jensen and Søren Brunak

PLOS Computational Biology, 2010, vol. 6, issue 5, 1-11

Abstract: Exposure to environmental chemicals and drugs may have a negative effect on human health. A better understanding of the molecular mechanism of such compounds is needed to determine the risk. We present a high confidence human protein-protein association network built upon the integration of chemical toxicology and systems biology. This computational systems chemical biology model reveals uncharacterized connections between compounds and diseases, thus predicting which compounds may be risk factors for human health. Additionally, the network can be used to identify unexpected potential associations between chemicals and proteins. Examples are shown for chemicals associated with breast cancer, lung cancer and necrosis, and potential protein targets for di-ethylhexyl-phthalate, 2,3,7,8-tetrachlorodibenzo-p-dioxin, pirinixic acid and permethrine. The chemical-protein associations are supported through recent published studies, which illustrate the power of our approach that integrates toxicogenomics data with other data types.Author Summary: Exposure to environmental chemicals and drugs may have a negative effect on human health. An essential step towards understanding the effect of chemicals on human health is to identify all possible molecular targets of a given chemical. Recently, various network-oriented chemical pharmacology approaches have been published. However, these methods limit the protein prediction to already known molecular drug targets. New findings can for example be made by using high-confidence protein-protein association databases. Here, we describe a generic, computational systems biology model with the aim of understanding the underlying molecular mechanisms of chemicals and the biological pathways they perturb. We present a novel and complementary approach to existing models by integrating toxicogenomics data, chemical structures, protein-protein interaction data, disease information and functional annotation of proteins. The high confidence protein-protein association network proposed reveals unexpected connections between chemicals and diseases or human proteins. We provide literature support to demonstrate the validity of some predictions, and thereby illustrate the power of an approach that integrates toxicogenomics data with other data types.

Date: 2010
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1000788

DOI: 10.1371/journal.pcbi.1000788

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