Ultrahigh-Resolution Mass Spectrometry-Based Platform for Plasma Metabolomics Applied to Type 2 Diabetes Research,Journal of Proteome Research

当前位置： X-MOL 学术 › J. Proteome Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Ultrahigh-Resolution Mass Spectrometry-Based Platform for Plasma Metabolomics Applied to Type 2 Diabetes Research
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-10-15 , DOI: 10.1021/acs.jproteome.0c00510
Yanlong Zhu _{1,

2} , Benjamin Wancewicz ₁ , Michael Schaid _{3,

4} , Timothy N Tiambeng ₅ , Kent Wenger _{1,

2} , Yutong Jin ₅ , Heino Heyman ₆ , Christopher J Thompson ₆ , Aiko Barsch ₇ , Elizabeth D Cox ₈ , Dawn B Davis _{3,

4} , Allan R Brasier ₉ , Michelle E Kimple _{1,

3,

4} , Ying Ge _{1,

2,

5}

Affiliation

Metabolomics—the endpoint of the omics cascade—is increasingly recognized as a preferred method for understanding the ultimate responses of biological systems to stress. Flow injection electrospray (FIE) mass spectrometry (MS) has advantages for untargeted metabolic fingerprinting due to its simplicity and capability for high-throughput screening but requires a high-resolution mass spectrometer to resolve metabolite features. In this study, we developed and validated a high-throughput and highly reproducible metabolomics platform integrating FIE with ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS for analysis of both polar and nonpolar metabolite features from plasma samples. FIE-FTICR MS enables high-throughput detection of hundreds of metabolite features in a single mass spectrum without a front-end separation step. Using plasma samples from genetically identical obese mice with or without type 2 diabetes (T2D), we validated the intra and intersample reproducibility of our method and its robustness for simultaneously detecting alterations in both polar and nonpolar metabolite features. Only 5 min is needed to acquire an ultra-high resolution mass spectrum in either a positive or negative ionization mode. Approximately 1000 metabolic features were reproducibly detected and annotated in each mouse plasma group. For significantly altered and highly abundant metabolite features, targeted tandem MS (MS/MS) analyses can be applied to confirm their identity. With this integrated platform, we successfully detected over 300 statistically significant metabolic features in T2D mouse plasma as compared to controls and identified new T2D biomarker candidates. This FIE-FTICR MS-based method is of high throughput and highly reproducible with great promise for metabolomics studies toward a better understanding and diagnosis of human diseases.

中文翻译：

基于超高分辨率质谱的血浆代谢组学平台应用于 2 型糖尿病研究

代谢组学——组学级联的终点——越来越被认为是了解生物系统对压力的最终反应的首选方法。流动注射电喷雾 (FIE) 质谱 (MS) 由于其简单性和高通量筛选能力而在非靶向代谢指纹识别方面具有优势，但需要高分辨率质谱仪来解析代谢物特征。在本研究中，我们开发并验证了一种高通量、高重现性的代谢组学平台，该平台将 FIE 与超高分辨率傅里叶变换离子回旋共振 (FTICR) MS 相结合，用于分析血浆样品的极性和非极性代谢物特征。FIE-FTICR MS 无需前端分离步骤即可高通量检测单个质谱中的数百种代谢物特征。使用来自患有或不患有 2 型糖尿病 (T2D) 的基因相同的肥胖小鼠的血浆样本，我们验证了我们方法的样本内和样本间重现性及其同时检测极性和非极性代谢物特征变化的稳健性。在正或负电离模式下，只需 5 分钟即可获得超高分辨率质谱图。在每个小鼠血浆组中可重复检测和注释大约 1000 个代谢特征。对于显着改变和高丰度的代谢物特征，可以应用靶向串联 MS (MS/MS) 分析来确认其身份。通过这个集成平台，与对照组相比，我们成功地检测到了 T2D 小鼠血浆中超过 300 种具有统计学意义的代谢特征，并确定了新的 T2D 生物标志物候选者。

更新日期：2020-10-15

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11