Ultrahigh-Resolution Mass Spectrometry-Based Platform for Plasma Metabolomics Applied to Type 2 Diabetes Research
Autor: | Christopher J. Thompson, Benjamin Wancewicz, Kent Wenger, Ying Ge, Aiko Barsch, Michelle E. Kimple, Yanlong Zhu, Allan R. Brasier, Heino M. Heyman, Yutong Jin, Dawn Belt Davis, Michael D. Schaid, Timothy N. Tiambeng, Elizabeth D. Cox |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Reproducibility Electrospray Chromatography 030102 biochemistry & molecular biology Resolution (mass spectrometry) Metabolite Reproducibility of Results General Chemistry Mass spectrometry Biochemistry Article Fourier transform ion cyclotron resonance Mice Plasma 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Metabolomics Diabetes Mellitus Type 2 chemistry Tandem Mass Spectrometry Mass spectrum Animals |
Zdroj: | J Proteome Res |
ISSN: | 1535-3907 1535-3893 |
Popis: | 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. |
Databáze: | OpenAIRE |
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