Metabolomics
From Biocrawler, the free encyclopedia.
Metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically, the study of their small-molecule metabolite profiles[1] (http://www.biocrawler.com/encyclopedia/Metabolomics#endnote_title_definition) The metabolome represents the collection of all metabolites in a biological organism, which are the end products of its gene expression. Thus, while mRNA gene expression data and proteomic analyses do not tell the whole story of what might be happening in a cell, metabolic profiling can give an instantaneous 'snapshot' of the physiology of that cell. One of the challenges of systems biology is to integrate proteomics, transcriptomics, and metabolomics information to give a more complete picture of living organisms.
The word metabonomics is also used, particularly in the context of drug toxicity assessment. There is some disagreement over the exact differences between 'metabolomics' and 'metabonomics'; in general, the term 'metabolomics' is more commonly used.
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History
One view of the origins of the field of metabolomics holds that it began with Linus Pauling's work toward "orthomolecular medicine" and his hypotheses regarding the predictive capacity of chromatographic profiling of bodily fluids for detection and diagnosis of human disease. Nonetheless, the chromatographic separation techniques that made the initial detection of metabolites possible were developed in the late 1960's, which marks the technical origin of the field.[2] (http://www.biocrawler.com/encyclopedia/Metabolomics#endnote_history)
Key technologies
- Mass spectrometry particularly gas chromatography mass spectrometry (GC MS), and liquid chromatography mass spectrometry (LC MS). In addition, direct-infusion mass spectrometry is becoming increasingly popular, especially for high-resolution techniques such as Fourier-transform ion-cyclotron-resonance mass spectrometry (FT-ICR-MS).
- High performance liquid chromatography (HPLC). Compared to GC, HPLC has inherently lower chromatographic resolution, but it does have the advantage that a much wider range of analytes can potentially be measured (whereas GC is limited to analysis of metabolites that are either volatile or can be made volatile by chemical derivatization).
- Nuclear magnetic resonance (NMR) spectrometry. NMR has a number of benefits as a metabolomics technique. There is no need for derivatization nor separation of the analytes, and the sample can thus be recovered for further analyses. All kinds of small molecule metabolite can be measured simultaneously - NMR is close to being a universal detector. However, it also possesses one major disadvantage, which is that it is relatively insensitive compared to mass spectrometry-based techniques.
- Capillary electrophoresis-mass spectrometry. So far, there are only a relatively small number of publications on use of CE-MS for metabolite profiling. This will no doubt change, as there are a number of advantages of CE-MS: it has a higher theoretical separation efficiency than HPLC, and is suitable for use with a wider range of metabolite classes than is GC.
Key applications
- Toxicity assessment/toxicology. Metabolic profiling (especially of urine or blood plasma samples) can be used to detect the physiological changes caused by toxic insult of a chemical (or mixture of chemicals). In many cases, the observed changes can be related to specific syndromes, e.g. a specific lesion in liver or kidney. This is of particular relevance to pharmaceutical companies wanting to test the toxicity of potential drug candidates: if a compound can be eliminated before it reaches clinical trials on the grounds of adverse toxicity, it saves the enormous expense of the trials.
- Functional genomics. Metabolomics can be an excellent tool for determining the phenotype caused by a genetic manipulation, such as gene deletion or insertion. Sometimes this can be a sufficient goal in itself -- for instance, to detect any phenotypic changes in a genetically-modified plant intended for human or animal consumption. More exciting is the prospect of predicting the function of unknown genes by comparison with the metabolic perturbations caused by deletion/insertion of known genes. Such advances are most likely to come from model organisms such as Saccharomyces cerevisiae and Arabidopsis thaliana.
- Nutrigenomics is a generalised term which links genomics, transcriptomics, proteomics and metabolomics to human nutrition. In general a metabolome in a given body fluid is influenced by endogenous factors such as age, sex, body composition and genetics as well as underlying pathologies. The large bowel microflora are also a very significant potential confounder of metabolic profiles and could be classified as either an endogenous or exogenous factor. The main exogenous factors are diet and drugs. Diet can then be broken down to nutrients and non- nutrients. Metabolomics is one means to determine a biological endpoint, or metabolic fingerprint, which reflects the balance of all these forces on an individual's metabolism. Please consult the external link to NuGo below
External link
- Metabolomics Society (http://www.metabolomicssociety.org/)
- Metabolomic Analysis at the University of California Davis (http://fiehnlab.ucdavis.edu/)
- The European Nutrigenomics Network (http://www.nugo.org/everyone)
See also
Notes
- ^ B. Daviss, "Growing pains for metabolomics," The Scientist, 19[8]:25-28, April 25, 2005.
- ^ Preti, George, "Metabolomics comes of age?" The Scientist, 19[11]:8, June 6, 2005.
