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Emory University Team Assembling Cancer 'Exposome' Atlas


NEW YORK — Scientists at Emory University are creating an exposomics data resource for cancer, which they believe can add key information on top of family history and other multiomics data and bolster understanding of malignancies.

"If we only consider heritability when we're trying to understand disease risk, we're really taking an unbalanced view of human health," Douglas Walker, an associate professor at Emory University's Rollins School of Public Health, said during a presentation at the Mayo Clinic's 11th annual Individualizing Medicine Conference last week.

Exposomics — the study of the cumulative exposures an individual experiences during their life — is a critical contributor to human health that complements insights from genomics, researchers said at the conference. Only between 5 percent and 15 percent of diseases can be attributed to inherited genetic factors, Walker estimated. The remaining 85 percent to 95 percent of the explanation for diseased states are attributable to the environment and lifestyle factors — for example, pollutants, pesticides, and chemicals — and their interaction with the genome. 

That's why Walker and his colleagues are creating exposome atlases, which could serve as a data resource for researchers studying the role of these various exposures on disease, starting with cancer. The vision for the Cancer Exposome Atlas is rooted in the Cancer Genome Atlas, a project led by the National Cancer Institute and the National Human Genome Research Institute, in which researchers sequenced thousands of samples and mapped DNA changes across different cancers. 

Similarly, "we hope to assemble this as an atlas and a resource for understanding how the exposome is linked to these different cancer outcomes," Walker said, adding that the exposure screening methods his team is using can be applied to many other diseases. In fact, this cancer-focused work is part of a broader effort by the Emory team to create various multiomic disease atlases that integrate data on exposomics, genomics, transcriptomics, epigenomics, microbiomics, and proteomics, so researchers can study the relationship between all this data and diseases.

In one of the first projects, Walker is studying the biological effects of benzene exposure and the chemical's link to leukemia, from which the team plans to start to assemble a Cancer Exposome Atlas. To advance this atlas, the researchers are conducting exposome screening on plasma and tissue samples from before and after patients were diagnosed with lung, breast, liver, and colon cancers.

Patients would be screened for biomarkers of exposures. While environmental factors can feel ambiguous — and as such, difficult to study — the exposome screening approach proposed by Walker focuses on measuring changes in the human metabolome as exposure biomarkers. For example, the chemical benzene is metabolized in the human body to produce phenol. The researchers therefore will test patients' samples for chemical compounds like phenol as biomarkers indicative of benzene exposure. 

The exposome disease atlases will be based on an approach to exposure screening developed by Walker, others at Emory, his former lab at the Icahn School of Medicine at Mount Sinai in New York City, and other researchers. The approach involves profiling the human metabolome to pinpoint biomarkers at the molecular level linked with chemical exposures.

For large-scale exposomics research, Walker said it’s "critical" to develop a framework for how to screen a person’s exposome in an "untargeted" way, which requires testing patients for numerous exposures, even ones that might not yet be linked with disease, instead of using tests that detect specific exposures. "It's a very, very complex entity to think about measuring," he said of the exposome. The goal is to "develop analytical methods that allow us to detect as many exposures as possible when they're present, then prioritize those based upon an outcome or some phenotype."

Another difficulty with exposomics research today, he said, is that the field is "fragmented." A lab might develop an assay to address specific research questions, but there aren't standards to ensure that samples are being tested and the results are being interpreted in a way that can be later shared or repurposed for other research.

The untargeted approach Walker proposed, outlined in a Nature Communications study last year, combines gas chromatography high-resolution mass spectrometry (GC-HRMS) and liquid chromatography high-resolution mass spectrometry (LC-HRMS) techniques to detect and screen for a range of biomarkers for known chemical exposures — certain carcinogenic chemical compounds and pesticides, for example — as well as unidentified chemical exposures and endogenous metabolites. Walker's team will conduct the mass spectrometry profiling on plasma and tissue samples. 

The team is also developing a library of standards for detecting signals of more than 7,300 chemicals related to various exposures, drugs, and commercial products using GC-HRMS and LC-HRMS assays. Having these standards, according to Walker, will help researchers identify chemicals more quickly in exposome studies. He and his colleagues are developing the standards based on resources from the US Environmental Protection Agency, IROA Technologies, and MetaSci.

Altogether, that approach "gives us the sensitivity and the robustness to provide functional measures for exposome-wide association studies," Walker said. "The use of these [GC-HRMS and LC-HRMS] platforms … allows us to start thinking about development of exposome-disease atlases."