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Optimization and application of direct infusion nanoelectrospray hrms method for large-scale urinary metabolic phenotyping in molecular epidemiology

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Title: Optimization and application of direct infusion nanoelectrospray hrms method for large-scale urinary metabolic phenotyping in molecular epidemiology
Authors: Chekmeneva, E
Dos Santos Correia
Nicholson, J
Holmes, E
Item Type: Journal Article
Abstract: Large-scale metabolic profiling requires the development of novel economical high-throughput analytical methods to facilitate characterization of systemic metabolic variation in population phenotypes. We report a fit-for-purpose direct infusion nanoelectrospray high-resolution mass spectrometry (DI-nESI-HRMS) method with time-of-flight detection for rapid targeted parallel analysis of over 40 urinary metabolites. The newly developed 2 min infusion method requires <10 μL of urine sample and generates high-resolution MS profiles in both positive and negative polarities, enabling further data mining and relative quantification of hundreds of metabolites. Here we present optimization of the DI-nESI-HRMS method in a detailed step-by-step guide and provide a workflow with rigorous quality assessment for large-scale studies. We demonstrate for the first time the application of the method for urinary metabolic profiling in human epidemiological investigations. Implementation of the presented DI-nESI-HRMS method enabled cost-efficient analysis of >10 000 24 h urine samples from the INTERMAP study in 12 weeks and >2200 spot urine samples from the ARIC study in <3 weeks with the required sensitivity and accuracy. We illustrate the application of the technique by characterizing the differences in metabolic phenotypes of the USA and Japanese population from the INTERMAP study.
Issue Date: 28-Feb-2017
Date of Acceptance: 28-Feb-2017
URI: http://hdl.handle.net/10044/1/45088
DOI: https://dx.doi.org/10.1021/acs.jproteome.6b01003
ISSN: 1535-3907
Publisher: American Chemical Society
Start Page: 1646
End Page: 1658
Journal / Book Title: Journal of Proteome Research
Volume: 16
Issue: 4
Copyright Statement: © 2017 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
Sponsor/Funder: University Of Northwestern
University Of Northwestern
National Institutes of Health
National Institutes of Health
Imperial College Healthcare NHS Trust- BRC Funding
National Institutes of Health
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: 0600 370 D315 586
1 RO1 HL50490
IMTERMAP Subaward No. 60024563
0600 370 D330 1362
RDC01 79560
60024563 ICL
Keywords: direct infusion mass spectrometry
high-throughput analysis
metabolic profiling
molecular epidemiology
Biochemistry & Molecular Biology
06 Biological Sciences
03 Chemical Sciences
Publication Status: Published
Appears in Collections:Department of Surgery and Cancer