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Environmental Factor, July 2015

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Metabolomics as a tool for exposure science

By Kelly Lenox

Patel Speaking

Patel, shown above at the January NIEHS workshop, when he chaired the workgroup on data science, is an assistant professor at the Harvard Center for Biomedical Informatics. (Photo courtesy of Steve McCaw)

Farland Speaking

Farland articulated the hopes of many of the experts present. “We are looking to do science that can enable action,” he said. (Photo courtesy of NRC)

Susan Sumner speaking

Panelist Susan Sumner, Ph.D., directs the National Institutes of Health Eastern Regional Comprehensive Metabolomics Research Center at RTI International, in Research Triangle Park, North Carolina. (Photo courtesy of NRC)

Experts in exposure science joined researchers in metabolomics at a Washington D.C. workshop held by the National Research Council (NRC), planned in conjunction with NIEHS. The May 28-29 event, “Metabolomics as a Tool for Characterizing the Exposome,” explored contributions that the science of metabolomics, which is the study of the chemical fingerprints that cellular processes leave behind, can make to the study of human exposures over the lifetime, which is known as the exposome.

Although significant challenges remain (see sidebar), the workshop demonstrated that metabolomics is a promising addition to exposure data obtained from monitors and sensors. “I think there are great possibilities for discovery,” said workshop moderator Chirag Patel, Ph.D., who is from Harvard University and serves on the NRC Standing Committee on Use of Emerging Science for Environmental Health Decisions , which sponsored the workshop.

Exposome studies provide insights into disease

Patel began by explaining that diseases generally result from interactions between genes and exposures. Genome-wide association studies help scientists understand genetic contributions, but exposure science is not as far along. “We lack [adequate] methods to ascertain and assess exposures,” Patel said, summarizing a January exposome workshop at NIEHS (see story), which led to this event.

David Balshaw, Ph.D., chief of the NIEHS Exposure, Response, and Technology Branch, provided the context for NIEHS. “The exposome features prominently in two of our strategic plan goals,” he said. Those goals include transforming exposure science, by helping to define the concept of the exposome and how it might be applied in research, as well as chemical mixtures research, which involves the study of interactions between environmental factors.

Stephen Rappaport, Ph.D. , from the University of California, Berkeley, pointed out that overall health may be affected by exposures, which can be seen as causal pathways, and the body’s responses to exposure, or reactive pathways. Rappaport explained that studying the metabolome through untargeted exposome-wide association studies may help identify disease biomarkers.

Challenges of metabolomics studies

Discussions between panelists and the audience made it clear that each aspect of mining the metabolome for exposure information is fraught with its own set of challenges.

For example, factors important in sample collection include the timing of collection with respect to exposure, one-time versus long-term collection, and preserving the right metadata, such as the known disease states of participants. Furthermore, both host genetics and bacterial genetics may drive effects in the body, so information on the microbiome is needed. Reproducibility was also discussed at length.

David Wishart, Ph.D. , from the University of Alberta, described several metabolomics databases, including the Human Metabolome Database , which contains free information on more than 40,000 metabolites. He emphasized that study of metabolites can be fast, cheap, and informative, and it is rapidly evolving. “It's in the early days still,” he said, “so these are exciting times.”


The way forward

Rappaport addressed the infrastructure necessary to moving forward. “It's a big enough … project that we need to get cooperation from government, academia, and industry, especially the industries that are involved with technology development,” he said.

William Farland, Ph.D., from Colorado State University and chair of the NRC standing committee, summed up the workshop with a look ahead. “The final discussion, about the chemists and toxicologists and epidemiologists getting together, [points out] that this is a big data problem that's going to require multidisciplinary types of approaches.”

NRC prepared a summary report and posted the agenda, speaker biographies and slides, and a video playlist on its webpage for the workshop .

Cohen Hubal Speaking

Elaine Cohen Hubal, Ph.D. from the U.S. Environmental Protection Agency, described the agency’s Chemical Safety for Sustainability research program, which provides tools to support production and use of safer chemicals. Prediction of exposure levels and effects are integral to that effort. (Photo courtesy of NRC)


“The greatest utility [of the exposome] will be in the area of disease etiology, or finding causes of disease,” said Rappaport, who is a lead researcher at the Berkeley Center for Exposure Biology. (Photo courtesy of NRC)

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