Metabolomics as a tool for exposure science
By Kelly Lenox
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.”
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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.