  Environmental contaminant exposure can pose significant risks to human
health. Therefore, evaluating the impact of this exposure is of great
importance; however, it is often difficult because both the molecular mechanism
of disease and the mode of action of the contaminants are complex. We used
network biology techniques to quantitatively assess the impact of environmental
contaminants on the human interactome and diseases with a particular focus on
seven major contaminant categories: persistent organic pollutants (POPs),
dioxins, polycyclic aromatic hydrocarbons (PAHs), pesticides,
perfluorochemicals (PFCs), metals, and pharmaceutical and personal care
products (PPCPs). We integrated publicly available data on toxicogenomics, the
diseasome, protein-protein interactions (PPIs), and gene essentiality and found
that a few contaminants were targeted to many genes, and a few genes were
targeted by many contaminants. The contaminant targets were hub proteins in the
human PPI network, whereas the target proteins in most categories did not
contain abundant essential proteins. Generally, contaminant targets and
disease-associated proteins were closely associated with the PPI network, and
the closeness of the associations depended on the disease type and chemical
category. Network biology techniques were used to identify environmental
contaminants with broad effects on the human interactome and
contaminant-sensitive biomarkers. Moreover, this method enabled us to quantify
the relationship between environmental contaminants and human diseases, which
was supported by epidemiological and experimental evidence. These methods and
findings have facilitated the elucidation of the complex relationship between
environmental exposure and adverse health outcomes.
