Deciphering Diseases and Biological Targets for Environmental Chemicals using Toxicogenomics Networks

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.

Human Environmental Disease Network: Deciphering disease-disease and chemicaldisease associations using chemical contaminants information_suppl

“…Chronic (long-term) inhalation exposure of procedure built on a neighbor protein procedure, which scores the associations between diseases, to the EDN model. The performance of this approach has been shown in previous studies (Audouze et al, 2010. Only the SE layer was used.…”

“…To predict diseases potentially linked to a chemical, a neighbor disease approach was performed based on the neighbor protein procedure described previously (Audouze et al, 2010). This approach is a multi-step procedure.…”

Advanced Molecular Biologic Techniques in Toxicologic Disease

“…For example, one statistical model based on known proteinchemical interactions is the Comparative Toxicogenomic Database (CTD). This system compares exposure to 2,490 chemicals and production of 6,060 proteins to identify 42,194 potential associations with specific adverse events [27]. For instances, di-ethylhexylphthalate (DEHP), a plasticizer for polyvinyl chlorate, is used in a variety of substances including intravenous tubing and nasogastric tubes.…”

“…PRKCE was then shown to be associated with brain tumor formation in a study evaluating TCDD neurotoxicity in cerebellar granule cells [32]. Therefore, the computational system biology approach may be useful in predicting specific toxicologic outcomes of specific exposures [27].…”

Human environmental disease network: A computational model to assess toxicology of contaminants

“…To develop our EDN, we took advantage of the computational network biology approach that we developed previously with toxicogenomics data (Audouze et al, 2010). The concept, originally based on Protein-Protein Associations Network (P-PAN), can be transposed to other areas of application and has shown success with experimental validation of novel associations between chemicals and biological targets .…”