SIMPEL: using stable isotopes to elucidate dynamics of context specific metabolism.


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
12 Feb 2024
Historique:
received: 03 08 2022
accepted: 23 01 2024
medline: 13 2 2024
pubmed: 13 2 2024
entrez: 12 2 2024
Statut: epublish

Résumé

The capacity to leverage high resolution mass spectrometry (HRMS) with transient isotope labeling experiments is an untapped opportunity to derive insights on context-specific metabolism, that is difficult to assess quantitatively. Tools are needed to comprehensively mine isotopologue information in an automated, high-throughput way without errors. We describe a tool, Stable Isotope-assisted Metabolomics for Pathway Elucidation (SIMPEL), to simplify analysis and interpretation of isotope-enriched HRMS datasets. The efficacy of SIMPEL is demonstrated through examples of central carbon and lipid metabolism. In the first description, a dual-isotope labeling experiment is paired with SIMPEL and isotopically nonstationary metabolic flux analysis (INST-MFA) to resolve fluxes in central metabolism that would be otherwise challenging to quantify. In the second example, SIMPEL was paired with HRMS-based lipidomics data to describe lipid metabolism based on a single labeling experiment. Available as an R package, SIMPEL extends metabolomics analyses to include isotopologue signatures necessary to quantify metabolic flux.

Identifiants

pubmed: 38347116
doi: 10.1038/s42003-024-05844-z
pii: 10.1038/s42003-024-05844-z
pmc: PMC10861564
doi:

Substances chimiques

Carbon Isotopes 0
Carbon 7440-44-0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

172

Subventions

Organisme : NIDDK NIH HHS
ID : P30 DK058404
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA235508
Pays : United States

Informations de copyright

© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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Auteurs

Shrikaar Kambhampati (S)

Donald Danforth Plant Science Center, St. Louis, MO, 63132, USA. skambhampati@salk.edu.
Jack H. Skirball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, CA, 92037, USA. skambhampati@salk.edu.

Allen H Hubbard (AH)

Donald Danforth Plant Science Center, St. Louis, MO, 63132, USA.

Somnath Koley (S)

Donald Danforth Plant Science Center, St. Louis, MO, 63132, USA.

Javier D Gomez (JD)

Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA.

Frédéric Marsolais (F)

London Research and Development Center, London, ON, N5V 4T3, Canada.
Department of Biology, University of Western Ontario, London, ON, N6A 5B7, Canada.

Bradley S Evans (BS)

Donald Danforth Plant Science Center, St. Louis, MO, 63132, USA.

Jamey D Young (JD)

Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37235, USA.

Doug K Allen (DK)

Donald Danforth Plant Science Center, St. Louis, MO, 63132, USA. doug.allen@ars.usda.gov.
Agricultural Research Service, US Department of Agriculture, St. Louis, MO, 63132, USA. doug.allen@ars.usda.gov.

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Classifications MeSH