A proposed framework to evaluate the quality and reliability of targeted metabolomics assays from the UK Consortium on Metabolic Phenotyping (MAP/UK).


Sarmad, Sarir, Viant, Mark R, Dunn, Warwick B ORCID: 0000-0001-6924-0027, Goodacre, Royston ORCID: 0000-0003-2230-645X, Wilson, Ian D ORCID: 0000-0002-8558-7394, Chappell, Katie E, Griffin, Julian L, O'Donnell, Valerie B, Naicker, Brendon, Lewis, Matthew R et al (show 2 more authors) (2023) A proposed framework to evaluate the quality and reliability of targeted metabolomics assays from the UK Consortium on Metabolic Phenotyping (MAP/UK). Nature protocols, 18 (4). pp. 1017-1027.

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Abstract

Targeted metabolite assays that measure tens or hundreds of pre-selected metabolites, typically using liquid chromatography-mass spectrometry, are increasingly being developed and applied to metabolic phenotyping studies. These are used both as standalone phenotyping methods and for the validation of putative metabolic biomarkers obtained from untargeted metabolomics studies. However, there are no widely accepted standards in the scientific community for ensuring reliability of the development and validation of targeted metabolite assays (referred to here as 'targeted metabolomics'). Most current practices attempt to adopt, with modifications, the strict guidance provided by drug regulatory authorities for analytical methods designed largely for measuring drugs and other xenobiotic analytes. Here, the regulatory guidance provided by the European Medicines Agency, US Food and Drug Administration and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use are summarized. In this Perspective, we have adapted these guidelines and propose a less onerous 'tiered' approach to evaluate the reliability of a wide range of metabolomics analyses, addressing the need for community-accepted, harmonized guidelines for tiers other than full validation. This 'fit-for-purpose' tiered approach comprises four levels-discovery, screening, qualification and validation-and is discussed in the context of a range of targeted and untargeted metabolomics assays. Issues arising with targeted multiplexed metabolomics assays, and how these might be addressed, are considered. Furthermore, guidance is provided to assist the community with selecting the appropriate degree of reliability for a series of well-defined applications of metabolomics.

Item Type: Article
Uncontrolled Keywords: UK Consortium on Metabolic Phenotyping (MAP/UK)
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 06 Mar 2023 13:55
Last Modified: 24 Aug 2023 01:30
DOI: 10.1038/s41596-022-00801-8
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3168749
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