Using the Blood Exposome to Discover Causes of Disease

Significance of the Topic

Chronic diseases account for the majority of worldwide mortality with cardiovascular disease and cancer leading the burden. Genetic factors explain only a small fraction of risk for common cancers, indicating that environmental exposures and their interactions with genes are primary drivers of chronic disease. A comprehensive approach to characterize the blood exposome is therefore critical to uncover causal exposures, enable early detection and guide personalized interventions.

Objectives and Overview of the Study

This technical overview introduces the blood exposome concept and proposes a two phase analytical workflow. Phase one consists of untargeted exposome wide association studies to discover chemicals that differentiate diseased individuals from healthy controls. Phase two involves targeted follow up investigations to verify candidate biomarkers, study exposure response relationships, clarify sources and kinetics, and elucidate mechanisms of action.

Methodology and Instrumentation

• Untargeted profiling uses high resolution liquid chromatography and gas chromatography coupled to time of flight mass spectrometers (LC TOF MS and GC TOF MS) to detect tens of thousands of molecular features in microliter volumes of blood or serum.
• Targeted follow up employs robotics and triple quadrupole mass spectrometry with multiple reaction monitoring for high throughput quantitation of verified exposures and disease biomarkers.
• Reactive electrophiles are characterized indirectly by profiling adducts formed at the Cys34 nucleophilic hotspot of human serum albumin using high resolution mass spectrometry.
• Data processing and statistical analysis utilize advanced bioinformatic platforms such as Mass Profiler Professional with pathway mapping tools to identify discriminating features and interpret their biological context.

Main Results and Discussion

Proof of concept studies have successfully identified previously unknown exposure biomarkers for colorectal cancer and cardiovascular disease, as well as biomarkers of disease progression in diabetes. Comparative analysis of blood exposomes demonstrates the ability to distinguish exposure derived indicators from reactive disease biomarkers. High sensitivity and multiplexing capability of the untargeted platforms meet the demands of exposome wide association studies in cohort settings.

Contributions and Practical Applications of the Method

• Novel biomarkers support early disease screening, risk assessment and monitoring of environmental toxicants.
• High throughput assays enable large scale epidemiological studies and quality control in clinical research laboratories.
• Exposome driven insights facilitate personalized medicine by linking specific exposures to disease etiology, progression and individual susceptibility.

Future Trends and Potential Applications

The field is poised to integrate multiple omic technologies including metallomics, metabolomics, proteomics and metagenomics, along with sensor arrays and advanced computational models. Enhanced sensitivity, throughput and data analytics will enable population level exposome mapping, causal inference in gene environment interactions and development of preventive public health strategies.

Conclusion

Exposomics unites epidemiology, toxicology, analytical chemistry and systems biology to reveal environmental determinants of chronic disease. A combined untargeted and targeted approach promises to accelerate discovery of causal exposures, advance early diagnostics, foster personalized interventions and improve population health outcomes.

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