Abstract
Metabolites, the chemical entities that are transformed during metabolism, provide a functional readout of cellular biochemistry. With emerging technologies in mass spectrometry, thousands of metabolites can now be quantitatively measured from minimal amounts of biological material, which has thereby enabled systems-level analyses. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanism are being revealed and are shaping our understanding of cell biology, physiology and medicine.
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Acknowledgements
The authors gratefully acknowledge that their work is supported by the California Institute of Regenerative Medicine (grant TR1-01219; G.S.), the US National Institutes of Health (grants R24 EY017540-04, P30 MH062261-10 and P01 DA026146-02; G.S.), the US Department of Energy (grants FG02-07ER64325 and DE-AC0205CH11231; G.S.), the US National Institutes of Health/National Institute on Aging (L30 AG0 038036; G.J.P.) and start-up funds from Washington University (G.J.P.).
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Glossary
- Imaging mass spectrometry
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A surface-based approach in which molecules such as metabolites and proteins are spatially analysed in biological specimens. Common imaging mass spectrometry techniques are matrix-assisted laser desorption ionization (MALDI), secondary ion mass spectrometry (SIMS) and nanostructure-initiator mass spectrometry (NIMS).
- Ion trap
-
A type of mass spectrometer that traps ions by using electric or magnetic fields. Once trapped, the ions are analysed to determine their mass-to-charge ratios. Tandem mass spectrometry can also be performed on selected ions by isolating them in the trap and then subjecting them to dissociation.
- Matrix-assisted laser desorption ionization
-
(MALDI). A surface-based mass spectrometry approach in which analytes are embedded in a chemical matrix that absorbs energy from an ultraviolet laser, resulting in analyte desorption and ionization.
- MS1 mode
-
The mode of a mass spectrometer in which only the mass-to-charge ratio of the intact ion is measured. In these experiments no tandem mass spectrometry is performed.
- Nanostructure-initiator mass spectrometry
-
(NIMS). A nanostructure surface-based mass spectrometry approach that does not require a matrix. NIMS is commonly used for metabolomic studies and metabolite imaging.
- Nuclear magnetic resonance
-
(NMR). An analytical technique that exploits the different responses to radiofrequency stimuli by chemically distinct atomic nuclei in an external magnetic field to provide information about the structure and dynamics of molecules.
- Quadrupole time-of-flight
-
(QTOF). A mass spectrometer commonly used to perform untargeted metabolomics. By using the quadrupole as a focusing lens, the time-of-flight mass analyser can be used to acquire profiling data. Alternatively, the quadrupole can be used to select ions for tandem mass spectrometry experiments.
- Tandem mass spectrometry
-
(MS/MS). A type of mass spectrometry in which ions are selectively isolated and then fragmented. The mass-to-charge ratio of each molecular fragment is measured and used for structural characterization.
- Triple quadrupole
-
(QqQ). A type of mass spectrometer that is often used for targeted studies owing to its sensitivity and specificity. The QqQ analyser consists of a quadrupole, a quadrupole collision cell and a second quadrupole, respectively. The first selects and analyses ions of interest, the second is used as a collision cell for fragmentation and the third analyses fragments.
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Patti, G., Yanes, O. & Siuzdak, G. Metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol 13, 263–269 (2012). https://doi.org/10.1038/nrm3314
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DOI: https://doi.org/10.1038/nrm3314
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