NEW 'OME' IN TOWN

We're living in an "omic" world. Some of these "omes," such as the genome and the proteome, are familiar; others, less so. Now the metabonome, one of the newest omes in name if not in reality, has joined the pantheon of global biological measurements.
METHOD OF CHOICE NMR is the most popular method for metabonomics experiments. The NMR facility at Imperial College is shown here.COURTESY OF JEREMY NICHOLSON The "omics" suffix has come to signify the measurement of the entire complement of a given level of biological molecules and information. Therefore, genomics measures the entire genetic makeup of an organism, while proteomics measures all the proteins expressed under given conditions. Metabonomics is no different. As the name might imply, metabonomics is defined as measurement of the complete metabolic response of an organism to an environmental stimulus or genetic modification. Some people use the term metabolomics to refer to metabonomics at the level of a single cell type, rather than a larger system.
The omics can provide information for basic biological research and for pharmaceutical and clinical applications. One of the challenges is integrating the information from the various omics, something that really is only beginning. The goal of a meeting held last month in San Francisco by the California Separation Science Society was just such an integration. In the process, the organizers coined yet another word--systeomics--which was defined as the integration of genomics, proteomics, and metabonomics.
Despite the goal of integration, scientists appear to be sticking with their favorite ome. Most speakers concentrated on one of the areas without addressing how to fit the three together.
Metabonomics may be the most recently named of the omics, but it's one of the oldest. In fact, metabonomics harkens back to old-fashioned biochemistry, with its emphasis on metabolism, the sum of the processes to acquire and use energy in an organism, to biosynthesize cellular components, and to catabolize wastes.
"We've been doing toxicological and disease diagnostics based on metabolic profiling for more than 20 years. That's before genomics or proteomics raised their ugly heads," Jeremy Nicholson, professor of biological chemistry at Imperial College of Science, Technology & Medicine in London, told C&EN.
Nicholson believes that metabonomics is "more closely related to things in the clinical world" than either genomics or proteomics, owing to the fact that metabonomic signatures reflect both genetic information and environmental influences.
John Lindon, another professor of biological chemistry at Imperial College, agrees. "Genomics and proteomics are in 'omics world.' They're not in the real world," Lindon said. "What you're trying to do is relate changes in gene expression or changes in protein level with some real-world endpoints that relate to a disease or toxic episode."
Adelbert Roscher, professor of biochemical genetics on the medical faculty at the University of Munich, said that metabolite profiling "measures the real outcome of potential changes suggested by genomics and proteomics."
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BIG PICTURE Metabonomics offers the opportunity to find patterns and changes in the entire metabolism, represented here by the metabolic pathways chart designed by Donald E. Nicholson, retired from the University of Leeds.©INTERNATIONAL UNION OF BIOCHEMISTRY & MOLECULAR BIOLOGYTHE VALUE OF genomic and proteomic measurements, Nicholson believes, is "considerably more limited than most people think." For example, changes in gene and protein expression needn't result in an "endpoint change." That is, the change in one gene or protein could be compensated elsewhere, resulting in no net change. "That's always the big problem with genes and proteins," Nicholson said. "Their up or down regulation can be part of the overall homeostatic or corrective process of the cell, not necessarily part of the pathology."
Nicholson suspects that most diseases have a metabolic signature at some level. The challenge is finding that signature. Finding the right matrix is important, whether it be urine, blood, cerebrospinal fluid, or solid tissue.
"Urine carries information on almost everything, because [the kidney is] your ultimate excretory organ, where homeostasis is maintained," Nicholson said. "There's a tremendous amount of information that can be obtained from urine, if you can analyze all the thousands of metabolites that are in there."
Metabonomics experiments are carried out by analyzing biological fluids or tissue extracts with techniques--such as nuclear magnetic resonance spectroscopy, mass spectrometry, or infrared spectroscopy--that provide many data points simultaneously. Even intact tissue samples taken during biopsies can be analyzed, using the NMR technique known as magic angle spinning.
The metabonomic profile is dominated by molecules smaller than 1,000 daltons. That molecular weight range "incorporates pretty much all energy pathways, all catabolic pathways, and many biosynthetic pathways," Nicholson told C&EN.
Nicholson and his colleagues focus on NMR measurements. The subtle differences in NMR spectra are practically impossible to identify just by visual inspection. Data mining and statistical techniques must be used to pull out what Nicholson calls "latent diagnostic information."