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Metabolomics. 2015;11:9-26. Epub 2014 Jul 25.

Molecular phenotyping of a UK population: defining the human serum metabolome.

Author information

1
Faculty of Engineering and Physical Sciences, School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK ; Faculty of Engineering & Physical Sciences, Manchester Centre for Integrative Systems Biology, Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK ; Faculty of Medical and Human Sciences, Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester, UK ; Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, M13 9WL UK ; School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
2
Faculty of Engineering and Physical Sciences, School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK ; Faculty of Medical and Human Sciences, Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester, UK ; Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, M13 9WL UK.
3
Faculty of Engineering and Physical Sciences, School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK ; Department of Medicine, Katz Group Centre for Pharmacy & Health, University of Alberta, Edmonton, AB T6G 2R3 Canada.
4
Faculty of Engineering and Physical Sciences, School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK.
5
Faculty of Engineering & Physical Sciences, School of Computer Science, The University of Manchester, Manchester, M13 9PL UK.
6
Faculty of Medical & Human Sciences, Institute of Inflammation and Repair, Salford Royal Dermatopharmacology, The University of Manchester, Manchester, M6 8HD UK.
7
Clinical & Cognitive Neurosciences, Faculty of Medical & Human Sciences, Institute of Brain, Behaviour & Mental Health, The University of Manchester, Manchester, M13 9PT UK.
8
Faculty of Medical and Human Sciences, Institute of Cancer Sciences, Christie Hospital, The University of Manchester, Manchester, M20 4BX UK.
9
Faculty of Engineering and Physical Sciences, School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK ; Faculty of Engineering & Physical Sciences, Manchester Centre for Integrative Systems Biology, Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK.
10
Faculty of Medical & Human Sciences, Institute of Human Development, The University of Manchester, Manchester, M13 9WL UK.
11
Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, Third Avenue, Harlow, Essex, CM19 5AW UK.
12
Faculty of Medical & Human Sciences, Institute of Cardiovascular Sciences, The University of Manchester, Manchester, M13 9PT UK ; St Thomas' Hospital, King's College, University of London & King's Health Partners, London, SE1 9NH UK.
13
Faculty of Medical & Human Sciences, Institute of Cardiovascular Sciences, The University of Manchester, Manchester, M13 9PT UK.
14
Investigative Preclinical Toxicology, GlaxoSmithKline, David Jack Centre for Research and Development, Park Road, Ware, Hertfordshire, SG12 0DP UK.
15
Faculty of Medicine, Department of Surgery & Cancer, Sir Alexander Fleming Building, Imperial College London, London, SW7 2AZ, UK ; DMPK Innovative Medicines, AstraZeneca, Cheshire, SK10 4TF UK.

Abstract

Phenotyping of 1,200 'healthy' adults from the UK has been performed through the investigation of diverse classes of hydrophilic and lipophilic metabolites present in serum by applying a series of chromatography-mass spectrometry platforms. These data were made robust to instrumental drift by numerical correction; this was prerequisite to allow detection of subtle metabolic differences. The variation in observed metabolite relative concentrations between the 1,200 subjects ranged from less than 5 % to more than 200 %. Variations in metabolites could be related to differences in gender, age, BMI, blood pressure, and smoking. Investigations suggest that a sample size of 600 subjects is both necessary and sufficient for robust analysis of these data. Overall, this is a large scale and non-targeted chromatographic MS-based metabolomics study, using samples from over 1,000 individuals, to provide a comprehensive measurement of their serum metabolomes. This work provides an important baseline or reference dataset for understanding the 'normal' relative concentrations and variation in the human serum metabolome. These may be related to our increasing knowledge of the human metabolic network map. Information on the Husermet study is available at http://www.husermet.org/. Importantly, all of the data are made freely available at MetaboLights (http://www.ebi.ac.uk/metabolights/).

KEYWORDS:

Clinical biochemistry; Human serum; Mass spectrometry; Metabolic phenotyping; UK population

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