Abstract
Metabolomics is a rapidly emerging field, whose progress has accelerated over the last decade. As a discipline, it has moved on from the refinement of analytical techniques and methodology toward a new phase where it is being applied to explore fundamental biological and clinical questions. We will address the evolution of metabolomics into an increasingly popular discipline and attempt to show its potential. This includes an overview of the technologies at the forefront of the field and other analytical techniques that provide information about the metabolome in diverse model systems. We will discuss mass spectrometry, NMR, and FTIR and chromatographic techniques that are critical to experimental protocols. Targeted and untargeted metabolomic study design is addressed along with some best practices and resources for practitioners of either methodology. A few technical and analytical hurdles remain, but new solutions continue to be presented. The promise of contemporary metabolomics is to contribute to a systems level understanding of biology and to usher in the era of precision medicine.
In this chapter, we introduce the field of metabolomics in the context of other omics disciplines. We emphasize the trend increased usage of omics technologies but metabolomics especially. We review the need for big-data approaches to modern science and their use. We define the terminologies used in metabolomics and describe the types of methodologies used in the context of the history of the discovery of the electron and the development of mass spectrometry. We discuss the applications of metabolomics and the development of the field.
The next section is a detailed review of methodologies in metabolomics regarding instrumentation (MS, NMR, FTIR, and other techniques). We then discuss separation techniques including principles of operation, covering the use and advantages of different solvent systems such as GC-MS, LC-MS, CE, and IMS. We then offer an overview of sample preparation as it pertains to metabolomics and list the cautions that must be taken when working with unstable or volatile metabolite extracts. We cover different study designs including targeted and untargeted metabolomics.
The final section details challenges that are common to all omics technologies, followed by challenges specific to metabolomics. We discuss technical hurdles to overcome and how they are currently addressed in the field. We conclude with a summary of the chapter and a look at the coming chapters and briefly discuss the coming advances in the field.
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Notes
- 1.
Note that we refer to omics technologies with reference to the actual methodologies – as opposed to the general concept of the comprehensive classification of a field.
- 2.
This is widely accepted to refer to biomolecules <1500 Da.
- 3.
We will focus on metabolomics exclusively in this text, but we refer the reader to an excellent text published by Springer for a thorough examination of proteomics [97].
- 4.
The Orbitrap Mass Analyzer is a version of the ion trap that is licensed exclusively to ThermoFisher Scientific. It is worth mentioning here because of its utility and popularity in metabolomics [98].
- 5.
Almost every MS manufacturer freely provides detailed information about the configuration of the detectors fitted to their instruments. There are many variations on the few that are listed here, but an exhaustive description of all the configurations is outside of the scope of this text.
- 6.
In actuality, when looking for a signal for glucose on a QqQ, commonly a signal is found at 73 m/z in negative mode; we will see why in the next section.
- 7.
Validation of a biomolecule refers to the unambiguous confirmation of a molecule’s identity (including an empirical formula) in a specific method, and it is not a trivial task. Fortunately, guidance exists for small molecules [99, 100], proteins [101], and lipids [102]. Additionally, the FDA offers its own guidance for small molecules [103] but has separate guidelines for validation of analytical methods [104].
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Hartman, T.E., Lees, H.J. (2023). Introduction of Metabolomics: An Overview. In: Soni, V., Hartman, T.E. (eds) Metabolomics. Springer, Cham. https://doi.org/10.1007/978-3-031-39094-4_1
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