Deciphering diseases and biological targets for environmental chemicals using toxicogenomics networks.
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.
Audouze
Karine
K
Department of Systems Biology, Technical University of Denmark, Center for Biological Sequence Analysis, Lyngby, Denmark.
Juncker
Agnieszka Sierakowska
AS
Roque
Francisco J S S A
FJ
Krysiak-Baltyn
Konrad
K
Weinhold
Nils
N
Taboureau
Olivier
O
Jensen
Thomas Skøt
TS
Brunak
Søren
S
D016000:Cluster Analysis; D030562:Databases, Protein; D004785:Environmental Pollutants / Q000032:analysis / Q000506:poisoning*; D005786:Gene Expression Regulation; D015386:Hazardous Substances / Q000032:analysis / Q000506:poisoning*; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced*; D025341:Principal Component Analysis; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000379:methods*; D015203:Reproducibility of Results; D049490:Systems Biology / Q000379:methods*; D043922:Toxicogenetics / Q000379:methods*
D004785:Environmental Pollutants; D015386:Hazardous Substances