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FAMetA: a mass isotopologue-based tool for the comprehensive analysis of fatty acid metabolism

View ORCID ProfileMaría Isabel Alcoriza-Balaguer, View ORCID ProfileJuan Carlos García-Cañaveras, View ORCID ProfileMarta Benet, View ORCID ProfileOscar Juan Vidal, View ORCID ProfileAgustín Lahoz
doi: https://doi.org/10.1101/2022.05.11.491462
María Isabel Alcoriza-Balaguer
1Biomarkers and Precision Medicine Unit, Medical Research Institute-Hospital La Fe, Av. Fernando Abril Martorell 106, Valencia, 46026, Spain
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  • ORCID record for María Isabel Alcoriza-Balaguer
Juan Carlos García-Cañaveras
1Biomarkers and Precision Medicine Unit, Medical Research Institute-Hospital La Fe, Av. Fernando Abril Martorell 106, Valencia, 46026, Spain
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Marta Benet
1Biomarkers and Precision Medicine Unit, Medical Research Institute-Hospital La Fe, Av. Fernando Abril Martorell 106, Valencia, 46026, Spain
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Oscar Juan Vidal
1Biomarkers and Precision Medicine Unit, Medical Research Institute-Hospital La Fe, Av. Fernando Abril Martorell 106, Valencia, 46026, Spain
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Agustín Lahoz
1Biomarkers and Precision Medicine Unit, Medical Research Institute-Hospital La Fe, Av. Fernando Abril Martorell 106, Valencia, 46026, Spain
3Analytical Unit, Medical Research Institute-Hospital La Fe, Av. Fernando Abril Martorell 106, Valencia, 46026, Spain
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  • For correspondence: agustin.lahoz@uv.es
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Abstract

The use of stable isotope tracers and mass spectrometry (MS) is the gold standard method for the analysis of fatty acids (FAs) metabolism. Yet current state-of-the-art tools provide limited information about FA biosynthetic routes. Here we present FAMetA, an R-package and a web-based application (www.fameta.es) that use 13C mass-isotopologue profiles to estimate not only FA import, synthesis and elongation, but also desaturation. The FAMetA workflow covers all the functionalities needed for MS data analyses. To illustrate its utility, different in vitro and in vivo experimental settings are used in which FA metabolism is modified. Thanks to the comprehensive characterisation of FA biosynthesis and the easy-to-interpret graphical representations compared to previous tools, FAMetA discloses unnoticed insights into how cells reprogramme their FA metabolism and, when combined with FASN, SCD1 and FADS2 inhibitors, it enables the straightforward identification of new FAs by the metabolic reconstruction of their synthesis route.

Competing Interest Statement

O.J. reports receiving honoraria for advisory roles from Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche/Genetech, AstraZeneca, Pfizer, Eli Lilly, AbbVie. A.L. reports receiving honoraria for advisory roles from AstraZeneca.

Footnotes

  • ↵* Email: agustin.lahoz{at}uv.es

  • https://zenodo.org/record/6511248#.YnuGqOhByUk

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 11, 2022.
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FAMetA: a mass isotopologue-based tool for the comprehensive analysis of fatty acid metabolism
María Isabel Alcoriza-Balaguer, Juan Carlos García-Cañaveras, Marta Benet, Oscar Juan Vidal, Agustín Lahoz
bioRxiv 2022.05.11.491462; doi: https://doi.org/10.1101/2022.05.11.491462
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FAMetA: a mass isotopologue-based tool for the comprehensive analysis of fatty acid metabolism
María Isabel Alcoriza-Balaguer, Juan Carlos García-Cañaveras, Marta Benet, Oscar Juan Vidal, Agustín Lahoz
bioRxiv 2022.05.11.491462; doi: https://doi.org/10.1101/2022.05.11.491462

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