Table of Contents
The next generation of “omics” paves way for integrated lifesciences research
- Metabolomics has been increasingly garnering a lot of interest as a suitable “omics” platform for use in drug discovery and development, post marketing surveillance, diagnosis; food and environment analysis; nutritional studies; and so on. Along with other “omics” platforms, it can be integrated into a systems biology toolkit.
- Developments in analytical methods have improved the sample extraction and preparation, and detection of multiple metabolites from complex mixtures, and the quest continues to improve sensitivity, detection limits of metabolites and ease of data analysis from metabolic profiles.
- Both metabolic fingerprinting (non quantitative) and metabolic profiling (quantitative) are used as complementary tools in basic and applied research.
- An increase in funding has been evident in the last xxyears with several federal grants allocated toward translational projects as well as basic research in metabolomics, and also to promote research collaborations.
- With developments in analytical techniques and metabolomic assay kits, adoption of metabolite biomarker tests is picking up, and can be used more widely in biological and pharmaceutical research.
Overview of Metabolomics
It is a nascent technology when compared to othe omics platforms that are increasingly being used for biomarker research, drug discovery, food and nutrition studies. It is a powerful tool and recent advances in LC-MS based metabolomics are enabling accurate measurement of metabolites in different types of samples such as, cell cultures, urine, saliva, and blood.
- Increasing number of biotech and pharmaceutical companies are incorporating research on metabolic biomarkers for drug discovery and clinical development. This is because of the high-biological relevance of biochemicals.
- Metabolomic analysis has the advantage to work with multiple samples types (tissues, blood, urine, food, and so on). Real-time picture of diseased cellular processes can be achieved with metabolomics analysis as the metabolome is more dynamic than proteome and genome.
- Small molecules are tested for in more than 90% of current diagnostic tests and most of drugs in the market and under development are small molecules.
- Altered metabolism is instrumental for development of several genetic and acquired diseases, and metabolomic analysis could be useful for discovery of biomarkers that could serve target for new drug or diagnostics development.
- The field of metabolic profiling has profound applications in various areas including food and nutritional studies, environmental studies, and so on.
- Due to the complexity of the metabolome (comprises both exogenous and endogenous metabolites), and diversity of chemicals, no single platform apt for detection of all metabolites.
- Different separation methods or combination of multiple separation and detection techniques are necessary for certain metabolite classes or sample types. The exhibit alongside lists out some of the major classes of metabolites that are studied using metabolomics experiments.
- Integrated platforms using multiple analytical methods or combining with other platforms can provide more coverage of metabolites.
- Metabolite extraction and separation is the first step for metabolite analysis, and developments in improvements in sample preparation with ionization techniques, such as DESI (desorption electrospray ionization), DART (direct analysis in real-time), and EESI (extractive electrospray ionization) are enabling use of direct MS in metabolomics studies.
- Automated platforms for sample preparation have also simplified metabolomics experiments to a certain extent, but they need to be more reproducible and standards have to be established.
- Mass spectrometry and nuclear magnetic resonance (NMR) are the main detection methods used and different types of mass spectrometers such as, quadrupole time-of-flight (QTOF) mass spectrometer, Orbitrap, MALDI, Triple Quadrupole, Ion Trap (non-FT) have different resolutions, sensitivity, selectivity, and need to be used according to the type of experiment (that is, targeted or untargeted)
- There are several databases for data storage and sharing (Human Metabolome Database [HMDB], Metlin, Metabolights] but the quest continues to expand on this and provide more comprehensive libraries.
- Sample preparation is a critical step in metabolomics studies, and it can have a major impact on the quality of data. This step is also important to improve the detection limits of metabolites from complex samples.
- Sample preparation must be absolutely reproducible, and standards need to be established.
- Ideally, sample preparation should contain as few steps as possible to reduce errors associated with each step, and the extraction conditions should capture the types of metabolites of interest.
- The common types of separation methods deployed in metabolomics studies are GC, LC, HPLC, CE. The choice of separation method depends on the number of analytes to be assessed, the concentration, type of metabolite, and so on.
- A few companies are working on developing internal standards to reduce the errors due to multiple sampling. By testing both control and sample in a single component, experimental errors can be reduced considerably (for example, NextGen Metabolomics).
- Automated sample preparation methods have also been developed for improving the quality and reducing time of large scale metabolomics studies significantly.
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