PT - JOURNAL ARTICLE AU - María Isabel Alcoriza-Balaguer AU - Juan Carlos García-Cañaveras AU - Marta Benet AU - Oscar Juan Vidal AU - Agustín Lahoz TI - FAMetA: a mass isotopologue-based tool for the comprehensive analysis of fatty acid metabolism AID - 10.1101/2022.05.11.491462 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.05.11.491462 4099 - http://biorxiv.org/content/early/2022/05/11/2022.05.11.491462.short 4100 - http://biorxiv.org/content/early/2022/05/11/2022.05.11.491462.full AB - 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 StatementO.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.