A proposed framework to evaluate the quality and reliability of targeted metabolomics assays from the UK Consortium on Metabolic Phenotyping (MAP/UK)
A proposed framework to evaluate the quality and reliability of targeted metabolomics assays from the UK Consortium on Metabolic Phenotyping (MAP/UK)
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DOI：
10.1038/s41596-022-00801-8
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发表时间：
2023-02-24
期刊：
影响因子：
14.8
通讯作者：
Suzuki，Toru
中科院分区：
文献类型：
--
作者：
Sarmad，Sarir;Viant，Mark R.;Suzuki，Toru
通常使用液相色谱-质谱法测量数十或数百种预先选择的代谢物的靶向代谢物测定法正在越来越多地被开发并应用于代谢表型研究。这些既可用作独立的表型分析方法，也可用于验证从非靶向代谢组学研究中获得的推定代谢生物标志物。然而，科学界没有广泛接受的标准来确保靶向代谢物测定（此处称为“靶向代谢组学”）开发和验证的可靠性。目前大多数实践都试图经过修改，采用药物监管机构为主要用于测量药物和其他外源分析物的分析方法提供的严格指导。本文总结了欧洲药品管理局、美国食品和药物管理局以及国际人用药品技术要求协调委员会提供的监管指南。在本视角中，我们对这些指南进行了调整，并提出了一种不太繁琐的“分层”方法来评估各种代谢组学分析的可靠性，满足了对除全面验证之外的社区接受的、统一的分层指南的需求。这种“适合目的”的分层方法包括四个层次——发现、筛选、鉴定和验证——并在一系列靶向和非靶向代谢组学检测的背景下进行讨论。考虑了靶向多重代谢组学检测中出现的问题以及如何解决这些问题。此外，还提供了指导，以帮助社区为一系列明确定义的代谢组学应用选择适当的可靠性程度。
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.