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

被引:16
作者
Zhu, Yanlong [1 ,2 ]
Wancewicz, Benjamin [1 ]
Schaid, Michael [3 ,4 ]
Tiambeng, Timothy N. [5 ]
Wenger, Kent [1 ,2 ]
Jin, Yutong [5 ]
Heyman, Heino [6 ]
Thompson, Christopher J. [6 ]
Barsch, Aiko [7 ]
Cox, Elizabeth D. [8 ]
Davis, Dawn B. [3 ,4 ]
Brasier, Allan R. [9 ]
Kimple, Michelle E. [1 ,3 ,4 ]
Ge, Ying [1 ,2 ,5 ]
机构
[1] Univ Wisconsin, Dept Cell & Regenerat Biol, Sch Med & Publ Hlth, Madison, WI 53705 USA
[2] Univ Wisconsin, Human Prote Program, Sch Med & Publ Hlth, Madison, WI 53705 USA
[3] Univ Wisconsin, Dept Med, Div Endocrinol Diabet & Metab, Madison, WI 53705 USA
[4] William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI 53705 USA
[5] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA
[6] Bruker Daltonics Inc, Billerica, MA 01821 USA
[7] Bruker Daltonik GmbH, D-28359 Bremen, Germany
[8] Univ Wisconsin, Dept Pediat, Madison, WI 53792 USA
[9] Univ Wisconsin, Inst Clin & Translat Res, Madison, WI 53705 USA
基金
美国国家卫生研究院;
关键词
Fourier transform ion cyclotron resonance mass spectrometry; flow injection electrospray; metabolite fingerprinting; plasma metabolomics; diabetes; high-throughput platform; HIGH-THROUGHPUT; MS; IDENTIFICATION; LIPIDOMICS; MELLITUS; METLIN;
D O I
10.1021/acs.jproteome.0c00510
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:463 / 473
页数:11
相关论文
共 69 条
[1]   High-throughput, nontargeted metabolite fingerprinting using nominal mass flow injection electrospray mass spectrometry [J].
Beckmann, Manfred ;
Parker, David ;
Enot, David P. ;
Duval, Emilie ;
Draper, John .
NATURE PROTOCOLS, 2008, 3 (03) :486-504
[2]   Cyclic dipeptides: from bugs to brain [J].
Bellezza, Ilaria ;
Peirce, Matthew J. ;
Minelli, Alba .
TRENDS IN MOLECULAR MEDICINE, 2014, 20 (10) :551-558
[3]   Quantitative profiling of bile acids in biofluids and tissues based on accurate mass high resolution LC-FF-MS: Compound class targeting in a metabolomics workflow [J].
Bobeldijk, Ivana ;
Hekman, Maarten ;
de Vries-van der Weij, Jitske ;
Coulier, Leon ;
Ramaker, Raymond ;
Kleemann, Robert ;
Kooistra, Teake ;
Rubingh, Carina ;
Freidig, Andreas ;
Verheij, Elwin .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2008, 871 (02) :306-313
[4]   Annotation of the human serum metabolome by coupling three liquid chromatography methods to high-resolution mass spectrometry [J].
Boudah, Samia ;
Olivier, Marie-Francoise ;
Aros-Calt, Sandrine ;
Oliveira, Lydie ;
Fenaille, Francois ;
Tabet, Jean-Claude ;
Junot, Christophe .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2014, 966 :34-47
[5]   Automated workflows for accurate mass-based putative metabolite identification in LC/MS-derived metabolomic datasets [J].
Brown, Marie ;
Wedge, David C. ;
Goodacre, Royston ;
Kell, Douglas B. ;
Baker, Philip N. ;
Kenny, Louise C. ;
Mamas, Mamas A. ;
Neyses, Ludwig ;
Dunn, Warwick B. .
BIOINFORMATICS, 2011, 27 (08) :1108-1112
[6]   Metabolomics applications of FT-ICR mass spectrometry [J].
Brown, SC ;
Kruppa, G ;
Dasseux, JL .
MASS SPECTROMETRY REVIEWS, 2005, 24 (02) :223-231
[7]   Quantitative analysis of biological membrane lipids at the low picomole level by nano-electrospray ionization tandem mass spectrometry [J].
Brugger, B ;
Erben, G ;
Sandhoff, R ;
Wieland, FT ;
Lehmann, WD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (06) :2339-2344
[8]   Validating Quantitative Untargeted Lipidomics Across Nine Liquid Chromatography-High-Resolution Mass Spectrometry Platforms [J].
Cajka, Tomas ;
Smilowitz, Jennifer T. ;
Fiehn, Oliver .
ANALYTICAL CHEMISTRY, 2017, 89 (22) :12360-12368
[9]   Tandem LC columns for the simultaneous retention of polar and nonpolar molecules in comprehensive metabolomics analysis [J].
Chalcraft, Kenneth R. ;
McCarry, Brian E. .
JOURNAL OF SEPARATION SCIENCE, 2013, 36 (21-22) :3478-3485
[10]   MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis [J].
Chong, Jasmine ;
Soufan, Othman ;
Li, Carin ;
Caraus, Iurie ;
Li, Shuzhao ;
Bourque, Guillaume ;
Wishart, David S. ;
Xia, Jianguo .
NUCLEIC ACIDS RESEARCH, 2018, 46 (W1) :W486-W494