title: Precision high-throughput proton NMR spectroscopy of human urine, serum, and plasma for large-scale metabolic phenotyping.
abstract: Proton nuclear magnetic resonance (NMR)-based metabolic phenotyping of urine and blood plasma/serum samples provides important prognostic and diagnostic information and permits monitoring of disease progression in an objective manner. Much effort has been made in recent years to develop NMR instrumentation and technology to allow the acquisition of data in an effective, reproducible, and high-throughput approach that allows the study of general population samples from epidemiological collections for biomarkers of disease risk. The challenge remains to develop highly reproducible methods and standardized protocols that minimize technical or experimental bias, allowing realistic interlaboratory comparisons of subtle biomarker information. Here we present a detailed set of updated protocols that carefully consider major experimental conditions, including sample preparation, spectrometer parameters, NMR pulse sequences, throughput, reproducibility, quality control, and resolution. These results provide an experimental platform that facilitates NMR spectroscopy usage across different large cohorts of biofluid samples, enabling integration of global metabolic profiling that is a prerequisite for personalized healthcare.
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Dona
authors.forename: Beatriz
authors.initials: B
authors.lastname: Jiménez
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schäfer
authors.forename: Eberhard
authors.initials: E
authors.lastname: Humpfer
authors.forename: Manfred
authors.initials: M
authors.lastname: Spraul
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Lewis
authors.forename: Jake T M
authors.initials: JT
authors.lastname: Pearce
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000652:urine; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000592:standards*; D055442:Metabolome; D055432:Metabolomics / Q000295:instrumentation / Q000592:standards*; D011522:Protons; D011786:Quality Control; D015203:Reproducibility of Results; D013048:Specimen Handling / Q000592:standards*
chemical_list: D015415:Biomarkers; D011522:Protons