Metabolomics

Metabolomics is the study of the metabolic profile of a given cell, tissue, fluid, organ or organism at a given point in time. The metabolome represents the end products of 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 (mRNA gene transcripts do not necessarily reflect either concentration or activity of a gene product in a cell, and do not account for posttranslational modifications; proteomic profiles are a lot closer to representing the 'actual' phenotype of a cell, but the presence/concentration of a protein still does not always reflect its biological activity), metabolites and their relative accumulation 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.

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 pressure 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.

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.

See also: proteomics, glycomics, DNA microarrays