What is metabolomics
The human body has several mysteries starting from the genome and ending with the whole body----and the study of metabolomics is one of them----call it advanced biochemistry that offers a link between genotypes and phenotypes. It is often referred to as metabonomics as well.
Metabolomics involves the analysis of biofluids (could be saliva, blood, urine and cerebrospinal fluids) and tissues to determine the extent of metabolites. As metabolism connotates phenotype integrating everything from nutritional aspects to the effects of environment to genetics, it is the only way to assess a person's health condition and provide a description of the cumulative state of an entire living being -----and that is possible only by studying the metabolome.
Metabolites are the end products of cellular processes, and the cumulative collection of metabolites in a cell, tissue, organ or organism is what is called a "metabolome. The University of Alberta report on the metabolome states that there are 2500 metabolites in the human metabolome although other researchers believe it may be on the lower side. These metabolites are usually small molecules with differences in molecular weights (wide range), concentrations and polarity. Researchers Fiehn and Weckworth have established that the metabolome is predictive of phenotype, because changes that occur in the metabolome indicate how the organism reacts to disease and genetic/environmental factors. Therefore, through the study of metabolomics or detailed profiling of metabolites one can reckon with disease diagnosis and other toxic effects on phenotype.
Metabolic profiling and metabolic fingerprinting
How are metabolomic evaluations done? There are two ways. The first possibility at the basic level involves the development of quantitative analytical methods for metabolites in a specific metabolic pathway----this is called metabolic profiling. A specific metabolic profile thus obtained is a standalone database and can be linked to other pathways. But when cumulative quantitative assessment of different metabolites from various other biochemical pathways is undertaken it's called metabolomics---that's when metabolic profiling becomes metabolomics. Metabolic profiling can be done on a single cell, whole organism or on substances such as urine, plasma and other body fluids.
Metabolic fingerprinting represents the other method. Herein individual compounds are not identified or quantitatively assessed, but on the contrary, metabolic patterns or fingerprints are assessed for their response to diseases or toxins. These fingerprints are often NMR or mass spectra or chromatogram data and the comparison is done using hierarchical cluster analysis (segregating the sample into unique metabolic clusters) which is a statistical tool---a tool that characteristically identifies groupings.
Metabolic profiling plus metabolic fingerprinting can be combined to give functional metabolomics----at one level fingerprint changes are correlated to metabolic profile and linked to a then prevailing physiological state (without being aware of fingerprint constituents)---in another approach key ingredients in the fingerprints become the subject matter for further quantitative metabolite analysis. Therefore, apart from contributing to our understanding of biology, if these biomarkers (metabolites that indicate a clinical endpoint---- the same way in which glucose levels are tagged to diabetes) can be analyzed in a specific assay it could become an excellent predictive diagnostic tool for the physician. The same way, there are biomarkers that signal drug safety and efficacy, or biomarkers that signal a drug's suitability for an individual.
Unlike typical aspects of physiology that have standalone role for specialists, "metabolomics" has a role for everyone---from analysts, toxicologists, molecular and computational biologists, nutritionists, physicians and many others.
Applications of metabolomics
Metabolic profiling gives insight into metabolic pathways, and how metabolites react with genes, proteins----and how they react with other factors emanating from nutritional aspects and the environment.
Metabolomics offers possibilities in profiling disease-related biochemical and signaling events. For example, concerning plants there are studies to show that certain soil bacteria produce antibiotics to save the plant from disease----and consequently a signaling mechanism is initiated between the plant and the bacteria in the soil which surrounds the plant roots (rhizosphere).Metabolomics helps to study this phenomenon.
Some metabolites are biologically active while others are sequestered which means they are in an inactive state. Metabolomics can show how to identify the biologically active fraction.
In future, metabolomics may be able to tell us where metabolites are located in the cell so that we can understand the role of metabolites in specific biochemical pathways.
Metabolomics can tell us about the etiology of disease and has contributed to both toxicology and toxicogenomics----and now we are beginning to see fruits by way of diagnostics and drug safety screening methodology. In short, the development of drug discovery oriented screening tools is one of the major offshoots of metabolomic research. The Consortium for Metabonomic Toxicology which is at the forefront of these research efforts have found out how to predict liver and kidney toxicity with respect to several compounds using NMR data.
Metabolomics can streamline the drug discovery process in terms of designing not too costly therapeutic targeting and can help in the development of early-stage toxicity screens----- and this means using lesser number of animals for research purposes. There are more uses of metabolomics in drug research. For example, a drug might induce an animal to lose weight in clinical studies and a researcher could attribute it to the drug's toxicity. But when metabolite profiling is done it might reflect a nutritional benefit rather than toxicity. This is one of the important aspects of metabolomic studies.
The extent of metabolites in biofluids can help diagnose certain genetic conditions and the physical condition of the human body in the aftermath of exposure to certain xenobiotics (a chemical that is not expected to be found in an organism but is nonetheless present.
Porphyria is a metabolic disorder that can only be diagnosed with metabolic tests that determine extent of porphyrin. Similarly, lactate to pyruvate ratio is determined for diagnosing zidovudine myopathy. Other metabolites especially amino acids and their derivatives that are usually evaluated in serum (using spectrophotometric methods) are glutamine, citrulline, arginine, ornithine, valine, leucine, isoleucine,aspartic acid, glutamic acid, phenylalanine, tyrosine, tryptophan, methionine, cystine, glycine,praline, alanine, threonine, lysine and hydroxyl-proline.
Analytical Methods Used in Metabolomics
It is wrong to completely assume that metabolomics is ordinary analytical chemistry that biologists and biochemists have been doing all along. That's because in order to completely decipher the metabolome, not only modern instrumentation like nuclear magnetic resonance is required but also multi-analytical platforms with high resolution and sensitivity.
Gas chromatography, liquid chromatography and capillary electrophoresis are the methods used for separation of metabolites. Thereafter, mass spectrometry (MS) is the most commonly used analytical technique, but at times it cannot quantify certain compounds.
At high metabolite concentrations NMR-based metabolic fingerprinting is usually effective as it can give both structural and quantitative data and also doesn't require much pre-analytical preparation as mass spectrometry (MS) needs. But the problem with NMR is the fact that its sensitivity depends on the strength of the magnet used and besides NMR data has to be statistically analyzed which needs trained personnel.
At lower metabolic concentrations mass spectrometry-based tools are used for metabolic fingerprinting. These are the analytical tools that have advanced the cause of metabolomics and all these instruments need software for data deconvolution. Either way, metabolomics has been confirmed as a vital parameter in physiological studies.
Research based companies in metabolomics
One of the leading metabolomic research companies is Metabolon----they deal in patented biochemical profiling platforms so that others can use them for analyzing biological samples in order to discover markers and mechanisms that can detect diseases early on (which means they can enable the profiling of metabolites in a given sample). Metabolon has also successfully used metabolomics for determining biomarkers for diseases such as "Amyotrophic Lateral Sclerosis, Alzheimer's disease, Parkinson's Disease, Huntington's Disease, depression and schizophrenia"
Phenomenome Discoveries Inc (PDI)
PDI is a company that separates and quantifies metabolites and is into biomarker discovery and represents the changing face of drug research. For example, PDI is researching human biofluids for finding out biomarkers that can forewarn metastatic cancer. Metastatic cancer is a cancer that originates in a tissue or organ somewhere in the body and that has spread to other organs----similarly research is also underway to find out biomarkers for autism.
Constraints in metabolomic research
Metabolites have divergent physical properties and concentration and differences of opinion persist regarding the definition of metabolites itself. For instance, since metabolites are defined as products of metabolism, should smaller peptides and vitamins be counted as such?
As a constituent of systems biology, the future of metabolomics lies in data-linking metabolic, genomic and proteomic data. In order to help with the integration of evolving metabolomic data with genomic and proteomic data it is important to have a basic database of metabolic profiles that are linked to protein and gene expression databases. Researchers must have access to isotopic labeled metabolite standards and pathway maps as that will help in data interpretation. That is one of the future challenges.
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