Liquid chromatography quadrupole time-of-flight mass spectrometry characterization of metabolites guided by the METLIN database
Zheng-Jiang Zhu,Andrew Schultz,Junhua Wang,Caroline H. Johnson,Steven M. Yannone,Gary J. Patti,Gary Siuzdak +6 more
TLDR
The protocol starts from untargeted metabolomic LC-Q-TOF-MS data that have been analyzed with the bioinformatics program XCMS, and it describes a strategy for selecting interesting features as well as performing subsequent targeted tandem MS.Abstract:
Untargeted metabolomics provides a comprehensive platform for identifying metabolites whose levels are altered between two or more populations. By using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS), hundreds to thousands of peaks with a unique m/z ratio and retention time are routinely detected from most biological samples in an untargeted profiling experiment. Each peak, termed a metabolomic feature, can be characterized on the basis of its accurate mass, retention time and tandem mass spectral fragmentation pattern. Here a seven-step protocol is suggested for such a characterization by using the METLIN metabolite database. The protocol starts from untargeted metabolomic LC-Q-TOF-MS data that have been analyzed with the bioinformatics program XCMS, and it describes a strategy for selecting interesting features as well as performing subsequent targeted tandem MS. The seven steps described will require 2-4 h to complete per feature, depending on the compound.read more
Citations
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Journal ArticleDOI
Emerging applications of metabolomics in drug discovery and precision medicine
TL;DR: This Review discusses some of the latest technological advances in metabolomics, focusing on the application of metabolomics towards uncovering the underlying causes of complex diseases, the growing role of metabolites in drug discovery and its potential effect on precision medicine.
Journal ArticleDOI
Mass spectral databases for LC/MS- and GC/MS-based metabolomics: state of the field and future prospects
TL;DR: The main characteristics of the mass spectral databases currently used in MS-based metabolomics are reviewed in this paper, underlining their advantages and limitations, and the overlap of compounds with MSn (n ≥ 2) spectra from authentic chemical standards in most public and commercial databases has been calculated for the first time.
Journal ArticleDOI
Identification of small molecules using accurate mass MS/MS search.
Tobias Kind,Hiroshi Tsugawa,Tomas Cajka,Yan Ma,Zijuan Lai,Sajjan S. Mehta,Gert Wohlgemuth,Dinesh Kumar Barupal,Megan R. Showalter,Masanori Arita,Oliver Fiehn,Oliver Fiehn +11 more
TL;DR: Parameters that influence search results, such as mass accuracy, precursor ion isolation width, intensity thresholds, centroiding algorithms, and acquisition speed are critically discussed.
Journal ArticleDOI
Ion mobility derived collision cross sections to support metabolomics applications.
Giuseppe Paglia,Jonathan P. Williams,Lochana C. Menikarachchi,J. Will Thompson,Richard Tyldesley-Worster,Skarphedinn Halldorsson,Ottar Rolfsson,Arthur Moseley,David F. Grant,James I. Langridge,Bernhard O. Palsson,Bernhard O. Palsson,Giuseppe Astarita,Giuseppe Astarita +13 more
TL;DR: The results indicate that adding CCS data to searchable databases and to routine metabolomics workflows will increase the identification confidence compared to traditional analytical approaches.
Journal ArticleDOI
Mass spectrometry-based metabolomics: a guide for annotation, quantification and best reporting practices
Saleh Alseekh,Asaph Aharoni,Yariv Brotman,Kévin Contrepois,John C. D’Auria,Jan Ewald,Jennifer C. Ewald,Paul D. Fraser,Patrick Giavalisco,Robert Hall,Matthias Heinemann,Hannes Link,Jie Luo,Steffen Neumann,Jens Nielsen,Leonardo Perez de Souza,Kazuki Saito,Uwe Sauer,Frank C. Schroeder,Stefan Schuster,Gary Siuzdak,Aleksandra Skirycz,Lloyd W. Sumner,Michael Snyder,Huiru Tang,Takayuki Tohge,Yulan Wang,Weiwei Wen,Si Wu,Guowang Xu,Nicola Zamboni,Alisdair R. Fernie +31 more
TL;DR: In this article, the authors present guidelines covering sample preparation, replication and randomization, quantification, recovery and recombination, ion suppression and peak misidentification, as a means to enable high-quality reporting of liquid chromatography and gas chromatography-mass spectrometry-derived data.
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