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Feature Articles : Apr 1, 2008 ( )
Metabolomics Studies Rise in Quality
HPLC, Mass Spec, and Nuclear Magnetic Resonance Are Among Elucidating Technologies
Metabolomics is the newest of the omics approaches and perhaps the one that is the closest reflection of what is actually taking place in the living cell. Researchers are looking to this platform, which draws on many different technologies, for new insights into biochemical pathways and hope it will thereby yield products such as biomarkers and new drug targets. Delegates at "metabomeeting 2008," which will take place later this month in Lyon, France, will present a range of specific contributions and approaches to metabolomics research.
John P. Shockcor, Ph.D., director of metabolic profiling business development at Waters, says that small molecule profiling (as metabolomics is sometimes known) is about four simple questions: what has gone up, what has gone down, what is missing, and what is new?
Waters’ HPLC/UPLC and mass spectrometry technologies can help answer these questions by providing information about the composition of complex molecular mixtures. Thereafter, it is the role of the biochemist to integrate this with proteomics and genomic data to understand the context of these changes that may, or may not lead to the identification of a useful biomarker.
Dr. Shockcor will present Waters’ recent work on ion mobility mass spectrometry—a technology that is the basis of the company’s Synapt high-definition MS (HDMS) system. Ion mobility refers to the diffusion of an ion through a gas under the influence of an electric field. The rate of this diffusion depends upon the charge on the ion and its rotational cross-sectional area—the latter being more relevant to metabolomic work.
The Waters system places an ion mobility separation stage just prior to the mass analyzer, and when combined with UPLC, a type of 2-D separation is achieved. The technology allows fine separation of ions with similar masses, and the output gives an accurate mass compared to the nominal mass, which is the more usual output of MS techniques.
Ion mobility with MS is a tool that Waters has pioneered, according to Dr. Shockcor, and other companies are now following its lead. “Waters will continue to develop ion-mobility mass spectrometry beyond the first generation and will focus upon the utility of accurate mass for analysis of complex mixtures,” he adds.
Synapt HDMS is already being used for a wide range of small molecule studies. Dr. Shockcor will discuss its application to lipidomics at the meeting. “So many of the chronic diseases that plague us, heart disease and diabetes, for instance, are linked to the regulation and absorption of lipids,” he explains. “There is a massive subset of tens of thousands of lipids that are extremely challenging to analyze in metabolomic studies. We are developing tools for looking at these in experiments that have not previously been possible.”
Nuclear Magnetic Resonance
Nuclear magnetic resonance (NMR) is another key technology for metabolomics, and Norbert Lutz, Ph.D., research professor at the Faculty of Medicine of the Université de la Méditerranée, will present some cutting-edge applications.
Studying a relatively large number of molecules through this approach can reveal the interdependence of biochemical processes and pathways and represents the complexity of cellular and tissue activity better than the more traditional approach of looking at only a few molecules. These are the important goals of biomedical research, he adds, and “it is hoped that metabolomics can lead to better diagnostics and the discovery of novel forms of therapy.”
As with the other omics, metabolomics can only be of value if dedicated and effective data-management systems are in place. At “metabomeeting,” Dr. Spasic will present MeMo, a data model she developed to support effective and efficient computational analysis of large volumes of experimental data generated through the use of high-throughput metabolomics technologies.
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