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Integrative Network Analysis Linking Clinical Outcomes With Environmental Exposures and Molecular Variations in
Juilee Thakar1, Thomas H Thatcher, Matthew Ryan Smith
1Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, Georgia (Dr Smith, Dr Walker, Dr Go, Dr Jones, Dr Uppal); Department of Microbiology & Immunology and Department of Biostatistics & computational Biology (Dr Thakar); Department of Environmental Medicine (Dr Thakar, Dr Utell); Department of Medicine, Pulmonary Division (Dr Thatcher, Dr Woeller, Dr Utell); Department of Public Health Sciences (Dr Hopke), University of Rochester Medical Center, Rochester, New York; Department of Preventive Medicine & Biostatistics, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda (Dr Mallon, Dr Krahl); Armed Forces Health Surveillance Center, Silver Spring (Ms Rohrbeck), Maryland.
Objective:
To develop a computational approach to link clinical outcomes with environmental exposures and molecular variations measured in Department of Defense (DOD) serum-repository samples.
Methods:
International Classification of Diseases, Ninth Division codes which corresponded to cardiopulmonary symptoms for service personnel were selected to test for associations with deployment-related inhalation hazards and metabolomics, micro-RNA, cytokine, plasma markers, and environmental exposure analyses for corresponding samples. xMWAS and Mummichog were used for integrative network and pathway analysis.
Results:
Comparison between 41 personnel exhibiting new cardio-pulmonary diagnoses after deployment start-date to 25 personnel exhibiting no symptoms identified biomarkers associated with cardiopulmonary conditions. Integrative network and pathway analysis showed communities of clinical, molecular, and environmental markers associated with fatty acid, lipid, nucleotide, and amino acid metabolism pathways.
Conclusions:
The current proof of principle study establishes a computational framework for integrative analysis of deployment-related exposures, molecular responses, and health outcomes.