Metabolomics Center offers technological window to
observe disease pathways
THE UC DAVIS ‘omics’ community recently received a boost with funding for the UC Davis West Coast Central Comprehensive Metabolomics Resource Core, known as the West Coast Metabolomics Center (WCMC). The funding of the WCMC – which was one of only three such core facilities initially funded by the National Institutes of Health (NIH) in September 2012 (the total has since increased to six) – acknowledges that UC Davis is at the forefront of metabolomics research. Housed within the Genome Center on the Davis campus, the WCMC is a consortium of eight research and service laboratories encompassing 35 mass spectrometers, five nuclear magnetic resonance instruments and advanced statistical software to process highly complex data. The explosion of improved computational and other technologies during the past 15 years has fostered evolution
“Metabolomics uses fast computers and new technologies to very broadly analyze numerous nutritional or xenobiotic compounds and endogenous metabolites in a short time frame,” explained Oliver Fiehn, professor of molecular and cellular biology and director of the WCMC. Using metabolomics methods, investigators can conduct studies not only in a hypothesis-driven approach, but also in a discovery-driven mode. That is the big distinction between classical clinical chemistry and the ‘omics’ disciplines. “A researcher investigating a complex disease is no longer constrained to a single hypothesis. Metabolomics can accommodate numerous variables by testing 50 or more hypotheses simultaneously,” said Fiehn. “Testing only one hypothesis is no longer considered innovative.”
Metabolomics offers a means of answering clinical questions in a way that is both novel and complementary to other disciplines. The object of interest in metabolomics studies – the metabolite – is the ultimate output of a cell, and as such, is much closer to the disease or “endpoint” that is clinically interesting. In other words, the metabolite is closer to the phenotype (observable characteristics) of an organism than the genotype (hereditary profile). Using genotypic data only, a scientist studying massive numbers of people may have difficulty linking genotypes studied with the phenotypes, or characteristics, of interest.
“Using the results of both metabolomics and genomics, you can trace your work from the metabolite level to genotypic variations,” Fiehn explains. “My lab has published at least eight papers on this topic. Together with a consortium led by Rima Kaddurah-Daouk [of Duke University], we used metabolomics to reveal the responses of clinical patients to pharmaceutical interventions in depression, hypertension, high cholesterol and other diseases. We mapped the biochemistry of patients with good responses to therapy and compared these findings with data from those who responded poorly. This information was then used to inform genome-wide association studies to identify SNPs that could potentially predict which patients – based on their genomic and metabolomic profiles at baseline – might benefit from therapy.”
The WCMC offers comprehensive, fee-based data analysis services for preclinical, clinical and translational science researchers. Fiehn describes the WCMC as a service center that responds to the basic and clinical research needs of the biomedical community. During the 2012–13 academic year, the center processed approximately 12,000 samples for 165 studies.
“We have a full-time statistician to help researchers with everything from power calculations and study design to pathway mapping and interpretation of data, which can be areas of difficulty for clinicians and metabolomics researchers,” Fiehn said. “We aid in study design and in the interpretation of data.”
The WCMC also has an Outreach and Promotion Core that includes educational offerings and a pilot program co-led by Lars Berglund, director of the UC Davis CTSC, and Alice Tarantal, director of the CTSC Pilot Translational and Clinical Studies Program and Translational Technologies, Methodologies and Resources Program. This past spring, in collaboration with the CTSC, the WCMC reviewed and funded pilot awards of up to $50,000 in metabolomic services for clinical and translational research studies. The pilot projects funded are focused on enriching existing human cohort or animal model studies, and supporting metabolomics research for new or ongoing studies.
“The CTSC helps researchers conduct pilot studies and organize reviews and ongoing evaluations of funded projects through progress reports,” Fiehn said. “We enrich CTSC educational programs by providing metabolomics instruction to physicians and biomedical researchers enrolled in their courses. Our services and courses are open to everyone, not just affiliates of the UC system, and we have projects with many clinicians and scientists across the U.S. We are working to build a relationship with other institutions in the CTSA consortium,” said Fiehn, who expects the WCMC to offer another pilot funding round within the next few months.
The WCMC conducts educational courses, symposia and monthly seminars explaining applications of metabolomics in translational science. Fiehn hopes that the center, which was established with a five-year, $9.3 million NIH startup grant in 2012, will be self-supporting by 2017.
For information visit http://metabolomics.ucdavis.edu where database applications and other software utilities are available for downloading.