title: Reproducibility of metabolomic profiles among men and women in 2 large cohort studies.
abstract: BACKGROUND
  Rigorous studies are necessary to demonstrate suitability of metabolomics platforms to profile metabolites in archived plasma within epidemiologic studies of human disease, for which attenuation of effect estimates due to measurement error is a key concern.
  
  
  METHODS
  Using a liquid chromatography-tandem mass spectrometry platform, we quantified 257 metabolites from archived plasma to evaluate metabolite interassay reproducibility, reproducibility with delayed processing, and within-person reproducibility over time. Interassay reproducibility was assessed with CVs from 60 duplicate plasma samples donated by participants in the Nurses' Health Study and Health Professionals Follow-up Study, and 20 QC pool plasma replicates. Metabolite reproducibility over a 24- to 48-h processing delay (n = 48 samples) and within-person reproducibility over 1-2 years (n = 80 samples) were assessed using Spearman and intraclass correlation coefficients (ICCs).
  
  
  RESULTS
  CVs were <20% for 92% of metabolites and generally were similar by plasma anticoagulant type (heparin or EDTA) and fasting time. Approximately 75% of metabolites were reproducible over delays in processing of blood samples (Spearman correlation or ICC ≥ 0.75, comparing immediate and 24-h delayed processing). Carbohydrates and purine/pyrimidine derivatives were most adversely affected by the processing delay. Ninety percent of metabolites were reproducible over 1-2 years within individuals (Spearman correlation or ICC ≥ 0.4).
  
  
  CONCLUSIONS
  For potential use in epidemiologic studies, the majority of plasma metabolites had low CVs and were reproducible over a 24-h processing delay and within individuals over 1-2 years. Certain metabolites, such as carbohydrates and purine/pyrimidine derivatives, may be challenging to evaluate if samples have delayed processing.
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA;
authors.forename: Mary K
authors.initials: MK
authors.lastname: Townsend
authors.forename: Clary B
authors.initials: CB
authors.lastname: Clish
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Souza
authors.forename: Amy A
authors.initials: AA
authors.lastname: Deik
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.forename: Brian M
authors.initials: BM
authors.lastname: Wolpin
mesh_terms: D000328:Adult; D000368:Aged; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D015203:Reproducibility of Results; D012737:Sex Factors; D053719:Tandem Mass Spectrometry
references.citation: Nature. 2011 Aug 31;477(7362):54-60
references.pmid: 21886157
references.citation: J Natl Cancer Inst. 1998 Sep 2;90(17):1292-9
references.pmid: 9731736
references.citation: Cancer Epidemiol Biomarkers Prev. 2001 Jan;10(1):65-8
references.pmid: 11205491
references.citation: Clin Chem. 1989 Dec;35(12):2313-6
references.pmid: 2591049
references.citation: J Clin Oncol. 2007 Apr 20;25(12):1482-8
references.pmid: 17372279
references.citation: BMC Clin Pathol. 2009 Nov 27;9:10
references.pmid: 19941666
references.citation: Int J Epidemiol. 2008 Apr;37 Suppl 1:i23-30
references.pmid: 18381390
references.citation: Circulation. 2012 May 8;125(18):2222-31
references.pmid: 22496159
references.citation: Cancer Causes Control. 2006 Sep;17(7):889-99
references.pmid: 16841256
references.citation: Clin Chem. 2005 Jan;51(1):230-2
references.pmid: 15613719
references.citation: Cytokine. 2009 Jan;45(1):44-9
references.pmid: 19058974
references.citation: Cancer Epidemiol Biomarkers Prev. 1995 Sep;4(6):649-54
references.pmid: 8547832
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1571-5
references.pmid: 20080599
references.citation: J Natl Cancer Inst. 2003 Mar 5;95(5):373-80
references.pmid: 12618502
references.citation: Clin Chem. 2003 Apr;49(4):652-5
references.pmid: 12651820
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):938-46
references.pmid: 20332276
references.citation: Epidemiology. 2008 Mar;19(2):338-44
references.pmid: 18300693
references.citation: N Engl J Med. 1981 Jan 8;304(2):65-70
references.pmid: 7442730
references.citation: Nature. 2009 Feb 12;457(7231):910-4
references.pmid: 19212411
references.citation: BMC Clin Pathol. 2007 Nov 12;7:9
references.pmid: 17997839
references.citation: Int J Obes Relat Metab Disord. 2001 Mar;25(3):346-53
references.pmid: 11319631
references.citation: Diabetes. 2013 Aug;62(8):2689-98
references.pmid: 23382451
references.citation: J Chromatogr A. 2006 Aug 25;1125(1):76-88
references.pmid: 16759663
references.citation: Clin Chem. 2013 May;59(5):833-45
references.pmid: 23386698
references.citation: Clin Chem Lab Med. 2008;46(9):1289-95
references.pmid: 18611105
references.citation: Cancer Epidemiol Biomarkers Prev. 1998 Oct;7(10):885-9
references.pmid: 9796633
references.citation: Clin Chem. 1990 Jan;36(1):81-7
references.pmid: 2297938
references.citation: Metabolomics. 2009 Dec;5(4):507-516
references.pmid: 20046864
references.citation: PLoS One. 2011;6(7):e21230
references.pmid: 21760889
references.citation: Nat Med. 2011 Apr;17(4):448-53
references.pmid: 21423183
references.citation: Am J Epidemiol. 1992 Dec 1;136(11):1400-13
references.pmid: 1488967
references.citation: J Clin Invest. 2011 Apr;121(4):1402-11
references.pmid: 21403394