New techniques, such as metabolite imaging, and improved analytical technologies are making metabolomics increasingly useful for a wider range of biomedical and pharmaceutical applications.
Metabolomics has already entered the clinic, with applications in newborn screening. Many other metabolomic-based clinical applications and tests are now emerging.
Metabolomics is revealing surprising metabolic causes and metabolite biomarkers for several prominant diseases such as diabetes, Alzheimer disease, atherosclerosis and cancer. These findings are identifying previously unsuspected therapeutic targets and novel potential therapeutic strategies.
Metabolomics is reducing the cost of toxicological screening, enabling improved clinical trial design, allowing better patient selection and monitoring and shortening the time needed for drugs to move through the development pipeline.
Metabolomics is beginning to play a part in precision medicine through the development of personalized phenotyping and individualized drug-response monitoring.
The use of metabolomics to phenotype tumours and to design custom cancer therapies represents the most 'cutting-edge' example of metabolomics enabling precision medicine.
Metabolomics is an emerging 'omics' science involving the comprehensive characterization of metabolites and metabolism in biological systems. Recent advances in metabolomics technologies are leading to a growing number of mainstream biomedical applications. In particular, metabolomics is increasingly being used to diagnose disease, understand disease mechanisms, identify novel drug targets, customize drug treatments and monitor therapeutic outcomes. This Review discusses some of the latest technological advances in metabolomics, focusing on the application of metabolomics towards uncovering the underlying causes of complex diseases (such as atherosclerosis, cancer and diabetes), the growing role of metabolomics in drug discovery and its potential effect on precision medicine.
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The author wishes to thank Genome Canada, the Canadian Institutes for Health Research (CIHR) and Alberta Innovates for financial support.
The author declares no competing financial interests.
- Metabolic phenotyping
The characterization of a cell, organism or biological system using metabolomics or metabolic profiling. Metabolic phenotyping is a method of describing the phenotype using chemical or metabolite readouts as a proxy for an organism's observable biochemical traits.
- Endogenous metabolites
Metabolites that are biosynthesized or potentially biosynthesized by the host organism and/or its endogenous microflora. Endogenous metabolites also include xenobiotics that have been metabolically transformed by the host.
- Exogenous metabolites
Xenobiotic metabolites or chemicals that the host (and/or its endogenous microflora) is not capable of biosynthesizing or that have not yet been metabolically transformed.
A branch of omics science that involves the study of the complete collection of environmental exposures (chemicals, foods, pollutants and pathogens) that a human is exposed to from conception onwards, which is referred to as the exposome.
- Coulometric array detectors
Multi-array electrochemical detection systems for detecting redox-active compounds as they elute from a high performance liquid chromatography (HPLC) column. Chemicals or metabolites react with specific electrodes in the detector depending on their redox potential.
- Inductively coupled plasma mass spectrometers
Mass spectrometers that are specifically designed to detect and quantify metals at very low concentrations. Metal ions are ionized by inductive heating to create an electrically conductive plasma that is then sent to a conventional mass spectrometer for detection.
- Evaporative light-scattering detectors
(ELSDs). Instruments that detect compounds eluting from a high-performance liquid chromatography (HPLC) system on the basis of light scattering rather than ultraviolet absorption or fluorescence. ELSDs permit the detection of far more compounds than other optical techniques.
- Secondary ion MS
(SIMS). A mass spectrometry (MS) technique that can be used to analyse and image the composition of thin films. Ions (that is, secondary ions) are generated by sputtering the surface of the sample with an intense ion beam.
- Desorption electrospray ionization MS
(DESI-MS). A mass spectrometry technique (MS) that uses atmospheric pressure ion sources to ionize samples in open air under ambient conditions. It is a combination of both electrospray and desorption ionization techniques wherein ionization occurs by spraying an electrically charged mist onto the sample surface.
The collection of microorganisms that reside in or on a larger organism, a larger organ or within a specific environmental niche.
The collection of chemical compounds that act on DNA as well as the collection of chemical modifications to DNA (and histones) that direct and/or alter the original instructions in the genome.
An agent (specifically, a chemical, protein or pathogen) that damages arteries leading to atherosclerosis or cardiovascular disease.
A metabolic process involving the catabolism of glutamine to generate energy as well as nitrogen and carbon byproducts. It is an important energy pathway for tumour cells.
- Mammalian target of rapamycin
(mTOR). A serine/threonine kinase that acts as a master controller of cell metabolism, cell growth, cell proliferation, cell survival and protein synthesis.
A field of information science that extracts useful information from chemical data using statistical or data-driven techniques.
A branch of omics science that involves the study of the microbiome.
A branch of metabolomics that involves the metabolomic analysis of both pharmaceutical compounds and endogenous metabolites after the administration of a pharmaceutical compound.
- Intronic SNP
A single nucleotide polymorphism (SNP) found in an intron or a non-coding region of a gene.
The metabolic equivalent of phenotypes. A metabotype is a metabolic profile that defines or classifies an individual's biochemical state at a given point in time.
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Wishart, D. Emerging applications of metabolomics in drug discovery and precision medicine. Nat Rev Drug Discov 15, 473–484 (2016). https://doi.org/10.1038/nrd.2016.32
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