Host Response to Environmental Hazards: Using Literature, Bioinformatics, and Computation to Derive Candidate Biomarkers of Toxic Industrial Chemical Exposure

Abstract : It is essential to protect Service Members from toxic and hazardous chemicals and materials across the entire range of deployment missions, from humanitarian to theater-level combat. Tools that rapidly and accurately quantify exposure-induced health effects would enable Commanders to make informed decisions on return-to-duty and allow service members to thrive in environments of uncertainty and danger. Currently, U.S. Forces lack a suitable method to rapidly screen and assess risk of toxic end organ injury following chemical exposures in the field. Markers of end-organ injury and toxicity and other health effects markers, particularly those used in a clinical setting, could be integrated into a lab-on-a-chip fieldable detection cartridge for molecular indicators of injury following chemical exposure or for routine surveillance when operating in dangerous environments. We utilized large public repositories of drug toxicity data to infer biomarkers of toxic industrial chemicals exposure. Using a computational and relational approach we prioritized militarily relevant toxic industrial chemicals and their anticipated adverse health effects, to include potential threats related to megacities. Initially, we focused on liver and kidney toxicity because these organs are particularly susceptible to toxic injury, often used in drug toxicity studies with large amounts of publically available data, and in some cases have established FDA-qualified biomarker panels or clinical assays. We mined the literature and databases (e.g., DrugMatrix and the Comparative Toxicogenomics Database) for candidate gene targets to make predictions about biomarkers related to toxic industrial chemicals that cause the same adverse health effects. We identified 78 and 244 gene modules associated with liver and kidney injury, respectively, and qualified some of these targets in independent animal studies.