Harmonizing human plasma metabolite annotation with Plasma Benchmark

IF 20.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Ville Koistinen, Topi Meuronen, Pekka Keski-Rahkonen, Reza Salek, Otto Savolainen, Hany Ahmed, Carl Brunius, Rikard Landberg, Marko Lehtonen, Seppo Auriola, Augustin Scalbert, Kati Hanhineva
{"title":"Harmonizing human plasma metabolite annotation with Plasma Benchmark","authors":"Ville Koistinen, Topi Meuronen, Pekka Keski-Rahkonen, Reza Salek, Otto Savolainen, Hany Ahmed, Carl Brunius, Rikard Landberg, Marko Lehtonen, Seppo Auriola, Augustin Scalbert, Kati Hanhineva","doi":"10.1038/s42255-025-01376-w","DOIUrl":null,"url":null,"abstract":"<p>The human plasma metabolome has been extensively characterized: version 5.0 of the Human Metabolome Database (HMDB)<sup>1</sup> currently encompasses 37,229 entries for metabolites reported in human blood. Although the analytical coverage of modern LC–MS platforms enables the detection and identification of 1,000–2,000 plasma metabolites, the number of well-known and regularly detected plasma metabolites is considerably smaller: reference values of 144 plasma metabolites in a healthy population<sup>2</sup> and 588 lipids in the National Institute of Standards and Technology’s (NIST) reference plasma sample<sup>3</sup> have been reported previously. The plasma metabolome also exhibits vast interindividual and intraindividual variability, which is explained by variation in the microbiome, dietary habits and genetics<sup>4</sup>. Challenges in consistently reporting the human plasma metabolome arise from interlaboratory variation in non-targeted LC–MS methodologies and varying practices and capabilities in the annotation of the metabolites themselves<sup>5</sup>.</p><p>To construct Plasma Benchmark, three participating laboratories analysed the same in-house pooled plasma and the NIST1950 human reference plasma<sup>6</sup> in four analytical modes, including reversed-phase and hydrophilic interaction chromatography in the positive and negative ionization modes followed by data matrix generation in MS-DIAL<sup>7</sup>. We applied a set of inclusion criteria based on signal-to-noise ratio, relative standard deviation, sample-to-blank ratio, and acquisition of MS/MS data and predicted molecular formula to narrow the number of detected molecular features down to 639 robust molecular features that most probably represent actual plasma metabolites. Nearly 88% of the detected molecular features did not fulfil the signal-to-noise ratio and sample-to-blank ratio criteria, probably due to inherent noise and contaminants in LC–MS data but also because of high variability in the detection of many molecular features across laboratories<sup>8</sup> (Fig. 1b). Manual curation of the robust molecular features resulted in 288 unique metabolites, whereas the rest of the molecular features were classified as redundant molecular features and in-source fragments. The inclusion of four analytical modes was crucial for an extensive coverage of metabolites because most were detected in only one mode (Fig. 1b).</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"42 1","pages":""},"PeriodicalIF":20.8000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s42255-025-01376-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

The human plasma metabolome has been extensively characterized: version 5.0 of the Human Metabolome Database (HMDB)1 currently encompasses 37,229 entries for metabolites reported in human blood. Although the analytical coverage of modern LC–MS platforms enables the detection and identification of 1,000–2,000 plasma metabolites, the number of well-known and regularly detected plasma metabolites is considerably smaller: reference values of 144 plasma metabolites in a healthy population2 and 588 lipids in the National Institute of Standards and Technology’s (NIST) reference plasma sample3 have been reported previously. The plasma metabolome also exhibits vast interindividual and intraindividual variability, which is explained by variation in the microbiome, dietary habits and genetics4. Challenges in consistently reporting the human plasma metabolome arise from interlaboratory variation in non-targeted LC–MS methodologies and varying practices and capabilities in the annotation of the metabolites themselves5.

To construct Plasma Benchmark, three participating laboratories analysed the same in-house pooled plasma and the NIST1950 human reference plasma6 in four analytical modes, including reversed-phase and hydrophilic interaction chromatography in the positive and negative ionization modes followed by data matrix generation in MS-DIAL7. We applied a set of inclusion criteria based on signal-to-noise ratio, relative standard deviation, sample-to-blank ratio, and acquisition of MS/MS data and predicted molecular formula to narrow the number of detected molecular features down to 639 robust molecular features that most probably represent actual plasma metabolites. Nearly 88% of the detected molecular features did not fulfil the signal-to-noise ratio and sample-to-blank ratio criteria, probably due to inherent noise and contaminants in LC–MS data but also because of high variability in the detection of many molecular features across laboratories8 (Fig. 1b). Manual curation of the robust molecular features resulted in 288 unique metabolites, whereas the rest of the molecular features were classified as redundant molecular features and in-source fragments. The inclusion of four analytical modes was crucial for an extensive coverage of metabolites because most were detected in only one mode (Fig. 1b).

Abstract Image

与血浆基准相协调的人血浆代谢物注释
人类血浆代谢组已被广泛表征:人类代谢组数据库(HMDB)1 5.0版目前包含37,229个人类血液中报告的代谢物条目。尽管现代LC-MS平台的分析覆盖范围能够检测和鉴定1,000-2,000种血浆代谢物,但已知和定期检测的血浆代谢物的数量相当少:健康人群中144种血浆代谢物的参考值2和美国国家标准与技术研究所(NIST)参考血浆样品3中的588种脂质已被报道。血浆代谢组也表现出巨大的个体间和个体内部差异,这可以通过微生物组、饮食习惯和遗传的差异来解释。持续报告人类血浆代谢组的挑战来自于非靶向LC-MS方法的实验室间差异以及代谢物本身注释的不同实践和能力5。为了构建Plasma Benchmark,三个参与实验室以四种分析模式分析了相同的内部池等离子体和NIST1950人类参考等离子体6,包括正负电离模式下的反相和亲水相互作用色谱,然后在MS-DIAL7中生成数据矩阵。我们应用了一套基于信噪比、相对标准差、样本空白比、MS/MS数据采集和预测分子式的纳入标准,将检测到的分子特征数量缩小到639个最可能代表实际血浆代谢物的强大分子特征。近88%的检测到的分子特征不符合信噪比和样本空白比标准,这可能是由于LC-MS数据中固有的噪声和污染物,也可能是由于实验室中许多分子特征的检测具有很高的可变性8(图1b)。人工筛选得到288个独特的代谢物,而其余的分子特征被归类为冗余分子特征和源内片段。包含四种分析模式对于代谢物的广泛覆盖至关重要,因为大多数代谢物仅在一种模式下检测到(图1b)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Nature metabolism
Nature metabolism ENDOCRINOLOGY & METABOLISM-
CiteScore
27.50
自引率
2.40%
发文量
170
期刊介绍: Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信