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Metabolomics activity screening for identifying metabolites that modulate phenotype

Abstract

Metabolomics, in which small-molecule metabolites (the metabolome) are identified and quantified, is broadly acknowledged to be the omics discipline that is closest to the phenotype1,2,3. Although appreciated for its role in biomarker discovery programs, metabolomics can also be used to identify metabolites that could alter a cell's or an organism's phenotype. Metabolomics activity screening (MAS) as described here integrates metabolomics data with metabolic pathways and systems biology information, including proteomics and transcriptomics data, to produce a set of endogenous metabolites that can be tested for functionality in altering phenotypes. A growing literature reports the use of metabolites to modulate diverse processes, such as stem cell differentiation, oligodendrocyte maturation, insulin signaling, T-cell survival and macrophage immune responses. This opens up the possibility of identifying and applying metabolites to affect phenotypes. Unlike genes or proteins, metabolites are often readily available, which means that MAS is broadly amenable to high-throughput screening of virtually any biological system.

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Figure 1: MAS for the identification of endogenous metabolites that modulate phenotype.
Figure 2: MAS demonstrated in stem-cell differentiation, a mouse model of type 2 diabetes, T-cell function and activity, macrophage response to a fungal stimulus, and a remyelination model for multiple sclerosis.

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Acknowledgements

We gratefully acknowledge financial support from the National Institutes of Health (Grants R01 GM114368-03, P30 MH062261-10, P01 DA026146-02), and support was also received from Ecosystems and Networks Integrated with Genes and Molecular Assemblies (http://enigma.lbl.gov), a Scientific Focus Area Program at Lawrence Berkeley Laboratory for the US Department of Energy, Office of Science, Office of Biological and Environmental Research under Contract DE-AC02-05CH11231.

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Correspondence to Gary Siuzdak.

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Guijas, C., Montenegro-Burke, J., Warth, B. et al. Metabolomics activity screening for identifying metabolites that modulate phenotype. Nat Biotechnol 36, 316–320 (2018). https://doi.org/10.1038/nbt.4101

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