Globally Optimized Targeted Mass Spectrometry: Reliable Metabolomics Analysis with Broad Coverage

Haiwei Gu, Ping Zhang, Jiangjiang Zhu, Daniel Raftery

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Targeted detection is one of the most important methods in mass spectrometry (MS)-based metabolomics; however, its major limitation is the reduced metabolome coverage that results from the limited set of targeted metabolites typically used in the analysis. In this study we describe a new approach, globally optimized targeted (GOT)-MS, that combines many of the advantages of targeted detection and global profiling in metabolomics analysis, including the capability to detect unknowns, broad metabolite coverage, and excellent quantitation. The key step in GOT-MS is a global search of precursor and product ions using a single liquid chromatography-triple quadrupole (LC-QQQ) mass spectrometer. Here, focused on measuring serum metabolites, we obtained 595 precursor ions and 1"890 multiple reaction monitoring (MRM) transitions, under positive and negative ionization modes in the mass range of 60-600 Da. For many of the MRMs/metabolites under investigation, the analytical performance of GOT-MS is better than or at least comparable to that obtained by global profiling using a quadrupole-time-of-flight (Q-TOF) instrument of similar vintage. Using a study of serum metabolites in colorectal cancer (CRC) as a representative example, GOT-MS significantly outperformed a large targeted MS assay containing ∼160 biologically important metabolites and provided a complementary approach to traditional global profiling using Q-TOF-MS. GOT-MS thus expands and optimizes the detection capabilities for QQQ-MS through a novel approach and should have the potential to significantly advance both basic and clinical metabolic research.

Original languageEnglish (US)
Pages (from-to)12355-12362
Number of pages8
JournalAnalytical Chemistry
Volume87
Issue number24
DOIs
StatePublished - Dec 15 2015
Externally publishedYes

Fingerprint

Mass spectrometry
Metabolites
Ions
Metabolomics
Liquid chromatography
Mass spectrometers
Ionization
Assays
Monitoring

ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Globally Optimized Targeted Mass Spectrometry : Reliable Metabolomics Analysis with Broad Coverage. / Gu, Haiwei; Zhang, Ping; Zhu, Jiangjiang; Raftery, Daniel.

In: Analytical Chemistry, Vol. 87, No. 24, 15.12.2015, p. 12355-12362.

Research output: Contribution to journalArticle

Gu, Haiwei ; Zhang, Ping ; Zhu, Jiangjiang ; Raftery, Daniel. / Globally Optimized Targeted Mass Spectrometry : Reliable Metabolomics Analysis with Broad Coverage. In: Analytical Chemistry. 2015 ; Vol. 87, No. 24. pp. 12355-12362.
@article{0c2736dfc40745ed99537a4e3490c19f,
title = "Globally Optimized Targeted Mass Spectrometry: Reliable Metabolomics Analysis with Broad Coverage",
abstract = "Targeted detection is one of the most important methods in mass spectrometry (MS)-based metabolomics; however, its major limitation is the reduced metabolome coverage that results from the limited set of targeted metabolites typically used in the analysis. In this study we describe a new approach, globally optimized targeted (GOT)-MS, that combines many of the advantages of targeted detection and global profiling in metabolomics analysis, including the capability to detect unknowns, broad metabolite coverage, and excellent quantitation. The key step in GOT-MS is a global search of precursor and product ions using a single liquid chromatography-triple quadrupole (LC-QQQ) mass spectrometer. Here, focused on measuring serum metabolites, we obtained 595 precursor ions and 1{"}890 multiple reaction monitoring (MRM) transitions, under positive and negative ionization modes in the mass range of 60-600 Da. For many of the MRMs/metabolites under investigation, the analytical performance of GOT-MS is better than or at least comparable to that obtained by global profiling using a quadrupole-time-of-flight (Q-TOF) instrument of similar vintage. Using a study of serum metabolites in colorectal cancer (CRC) as a representative example, GOT-MS significantly outperformed a large targeted MS assay containing ∼160 biologically important metabolites and provided a complementary approach to traditional global profiling using Q-TOF-MS. GOT-MS thus expands and optimizes the detection capabilities for QQQ-MS through a novel approach and should have the potential to significantly advance both basic and clinical metabolic research.",
author = "Haiwei Gu and Ping Zhang and Jiangjiang Zhu and Daniel Raftery",
year = "2015",
month = "12",
day = "15",
doi = "10.1021/acs.analchem.5b03812",
language = "English (US)",
volume = "87",
pages = "12355--12362",
journal = "Analytical Chemistry",
issn = "0003-2700",
publisher = "American Chemical Society",
number = "24",

}

TY - JOUR

T1 - Globally Optimized Targeted Mass Spectrometry

T2 - Reliable Metabolomics Analysis with Broad Coverage

AU - Gu, Haiwei

AU - Zhang, Ping

AU - Zhu, Jiangjiang

AU - Raftery, Daniel

PY - 2015/12/15

Y1 - 2015/12/15

N2 - Targeted detection is one of the most important methods in mass spectrometry (MS)-based metabolomics; however, its major limitation is the reduced metabolome coverage that results from the limited set of targeted metabolites typically used in the analysis. In this study we describe a new approach, globally optimized targeted (GOT)-MS, that combines many of the advantages of targeted detection and global profiling in metabolomics analysis, including the capability to detect unknowns, broad metabolite coverage, and excellent quantitation. The key step in GOT-MS is a global search of precursor and product ions using a single liquid chromatography-triple quadrupole (LC-QQQ) mass spectrometer. Here, focused on measuring serum metabolites, we obtained 595 precursor ions and 1"890 multiple reaction monitoring (MRM) transitions, under positive and negative ionization modes in the mass range of 60-600 Da. For many of the MRMs/metabolites under investigation, the analytical performance of GOT-MS is better than or at least comparable to that obtained by global profiling using a quadrupole-time-of-flight (Q-TOF) instrument of similar vintage. Using a study of serum metabolites in colorectal cancer (CRC) as a representative example, GOT-MS significantly outperformed a large targeted MS assay containing ∼160 biologically important metabolites and provided a complementary approach to traditional global profiling using Q-TOF-MS. GOT-MS thus expands and optimizes the detection capabilities for QQQ-MS through a novel approach and should have the potential to significantly advance both basic and clinical metabolic research.

AB - Targeted detection is one of the most important methods in mass spectrometry (MS)-based metabolomics; however, its major limitation is the reduced metabolome coverage that results from the limited set of targeted metabolites typically used in the analysis. In this study we describe a new approach, globally optimized targeted (GOT)-MS, that combines many of the advantages of targeted detection and global profiling in metabolomics analysis, including the capability to detect unknowns, broad metabolite coverage, and excellent quantitation. The key step in GOT-MS is a global search of precursor and product ions using a single liquid chromatography-triple quadrupole (LC-QQQ) mass spectrometer. Here, focused on measuring serum metabolites, we obtained 595 precursor ions and 1"890 multiple reaction monitoring (MRM) transitions, under positive and negative ionization modes in the mass range of 60-600 Da. For many of the MRMs/metabolites under investigation, the analytical performance of GOT-MS is better than or at least comparable to that obtained by global profiling using a quadrupole-time-of-flight (Q-TOF) instrument of similar vintage. Using a study of serum metabolites in colorectal cancer (CRC) as a representative example, GOT-MS significantly outperformed a large targeted MS assay containing ∼160 biologically important metabolites and provided a complementary approach to traditional global profiling using Q-TOF-MS. GOT-MS thus expands and optimizes the detection capabilities for QQQ-MS through a novel approach and should have the potential to significantly advance both basic and clinical metabolic research.

UR - http://www.scopus.com/inward/record.url?scp=84950126258&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84950126258&partnerID=8YFLogxK

U2 - 10.1021/acs.analchem.5b03812

DO - 10.1021/acs.analchem.5b03812

M3 - Article

C2 - 26579731

AN - SCOPUS:84950126258

VL - 87

SP - 12355

EP - 12362

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 0003-2700

IS - 24

ER -