title: Contextualised urinary biomarker analysis facilitates diagnosis of paediatric obstructive sleep apnoea.
abstract: BACKGROUND
  Intrinsic variance of the urine proteome limits the discriminative power of proteomic analysis and complicates potential biomarker detection in the context of paediatric sleep disorders.
  
  
  RESULTS
  Using a rigorous workflow for proteomic analysis of urine, we demonstrate that gender and diurnal effects constitute two important sources of variability in healthy children. In the context of disease, complex pathophysiological perturbations magnify these proteomic differences and therefore require contextualised biomarker analysis. Indeed, by performing biomarker discovery in a gender- and diurnal-dependent manner, we identified ∼30-fold more candidate biomarkers of paediatric obstructive sleep apnoea (OSA), a highly prevalent condition in children characterised by repetitive episodes of intermittent hypoxia and hypercapnia, and sleep fragmentation in the context of recurrent upper airway obstructive events during sleep. Remarkably, biomarkers were highly specific for gender and sampling time as poor overlap (∼3%) was observed in the proteins identified in boys and girls across morning and bedtime samples.
  
  
  CONCLUSIONS
  As no clinical basis to explain gender-specific effects in OSA or healthy children is apparent, we propose that implementation of contextualised biomarker strategies will be applicable to a broad range of human diseases, and may be specifically applicable to paediatric OSA.
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Lev
authors.initials: L
authors.lastname: Becker
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Leila
authors.initials: L
authors.lastname: Kheirandish-Gozal
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Eduard
authors.initials: E
authors.lastname: Peris
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Kelly Q
authors.initials: KQ
authors.lastname: Schoenfelt
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA. Electronic address: dgozal@uchicago.edu.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D002940:Circadian Rhythm; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D010455:Peptides / Q000652:urine; D017286:Polysomnography; D011507:Proteinuria / Q000652:urine; D040901:Proteomics; D012737:Sex Factors; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000652:urine*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D010455:Peptides
keywords: Biomarkers; Diagnosis; Gender; Obstructive sleep apnoea; Paediatric; Urine proteomics
references.citation: Pediatrics. 2010 Nov;126(5):e1161-7
references.pmid: 20956420
references.citation: Ann N Y Acad Sci. 2012 Aug;1264:135-41
references.pmid: 22882312
references.citation: Anal Chem. 2007 Sep 15;79(18):6995-7004
references.pmid: 17702530
references.citation: J Proteome Res. 2006 Jan;5(1):112-21
references.pmid: 16396501
references.citation: Mol Cell Proteomics. 2012 Apr;11(4):M111.009449
references.pmid: 22159600
references.citation: Bioinformatics. 2010 Jun 15;26(12):1574-5
references.pmid: 20413636
references.citation: Am J Respir Crit Care Med. 2008 Feb 15;177(4):369-75
references.pmid: 17975198
references.citation: Bioinformatics. 2005 Aug 15;21(16):3448-9
references.pmid: 15972284
references.citation: J Physiol Pharmacol. 2005 Sep;56 Suppl 4:71-7
references.pmid: 16204778
references.citation: Proteomics Clin Appl. 2011 Jun;5(5-6):367-74
references.pmid: 21591268
references.citation: Sci Transl Med. 2010 Feb 24;2(20):20ra14
references.pmid: 20371490
references.citation: Clin Chem Lab Med. 2011 Nov 18;50(3):529-34
references.pmid: 22098435
references.citation: Respir Physiol Neurobiol. 2011 Sep 30;178(3):465-74
references.pmid: 21569868
references.citation: Acta Diabetol. 2012 Dec;49(6):453-64
references.pmid: 22678621
references.citation: Diabetes. 2012 Dec;61(12):3304-13
references.pmid: 22872235
references.citation: Anal Chem. 2002 Oct 15;74(20):5383-92
references.pmid: 12403597
references.citation: PLoS Genet. 2009 Aug;5(8):e1000602
references.pmid: 19680444
references.citation: Sleep Med. 2010 Aug;11(7):708-13
references.pmid: 20621557
references.citation: Cell Metab. 2010 Feb 3;11(2):125-35
references.pmid: 20142100
references.citation: J Biomol Tech. 2009 Apr;20(2):101-8
references.pmid: 19503621
references.citation: Nat Rev Clin Oncol. 2011 Aug 23;8(10):587-96
references.pmid: 21862978
references.citation: Pediatrics. 2006 Mar;117(3):741-53
references.pmid: 16510654
references.citation: Mol Cell Proteomics. 2005 Oct;4(10):1487-502
references.pmid: 15979981
references.citation: Curr Opin Pediatr. 2008 Dec;20(6):654-8
references.pmid: 19005334
references.citation: IEEE Trans Biomed Eng. 2013 Jan;60(1):164-8
references.pmid: 22893371
references.citation: Diabetes Technol Ther. 2010 Dec;12(12):979-88
references.pmid: 20735160
references.citation: Pediatr Int. 2011 Feb;53(1):1-6
references.pmid: 20840485
references.citation: Anal Chem. 2004 Jul 15;76(14):4193-201
references.pmid: 15253663
references.citation: Am J Respir Crit Care Med. 2008 May 15;177(10):1142-9
references.pmid: 18276939
references.citation: Sci Transl Med. 2012 Jul 11;4(142):142ra94
references.pmid: 22786679
references.citation: Cardiol Rev. 2012 May-Jun;20(3):111-7
references.pmid: 22301714
references.citation: Am J Respir Crit Care Med. 2011 Jun 15;183(12):1633-43
references.pmid: 21471098
references.citation: J Proteome Res. 2006 Jan;5(1):183-91
references.pmid: 16396510
references.citation: Anal Chem. 2003 Sep 1;75(17):4646-58
references.pmid: 14632076
references.citation: Mol Cell Proteomics. 2008 Feb;7(2):290-8
references.pmid: 17951555
references.citation: Chest. 2007 Mar;131(3):733-739
references.pmid: 17356087
references.citation: Ann Occup Hyg. 2004 Mar;48(2):171-9
references.pmid: 14990438
references.citation: Proteomics Clin Appl. 2007 Jun;1(6):577-87
references.pmid: 21136709
references.citation: Sleep Breath. 2014 Mar;18(1):13-8
references.pmid: 22903801
references.citation: Am J Respir Crit Care Med. 2009 Dec 15;180(12):1253-61
references.pmid: 19797158
references.citation: PLoS One. 2012;7(3):e33297
references.pmid: 22428014
references.citation: Genome Biol. 2006;7(9):R80
references.pmid: 16948836
references.citation: Proteomics. 2004 Jul;4(7):1985-8
references.pmid: 15221759