title: Proteomic analysis of ascending colon biopsies from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn's disease from UC.
abstract: Accurate differentiation between Crohn's disease (CD) and UC is important to ensure early and appropriate therapeutic intervention. We sought to identify proteins that enable differentiation between CD and UC in children with new onset IBD.
  
  
  
  Mucosal biopsies were obtained from children undergoing baseline diagnostic endoscopy prior to therapeutic interventions. Using a super-stable isotope labeling with amino acids in cell culture (SILAC)-based approach, the proteomes of 99 paediatric control and biopsies of patients with CD and UC were compared. Multivariate analysis of a subset of these (n=50) was applied to identify novel biomarkers, which were validated in a second subset (n=49).
  
  
  
  In the discovery cohort, a panel of five proteins was sufficient to distinguish control from IBD-affected tissue biopsies with an AUC of 1.0 (95% CI 0.99 to 1.0); a second panel of 12 proteins segregated inflamed CD from UC within an AUC of 0.95 (95% CI 0.86 to 1.0). Application of the two panels to the validation cohort resulted in accurate classification of 95.9% (IBD from control) and 80% (CD from UC) of patients. 116 proteins were identified to have correlation with the severity of disease, four of which were components of the two panels, including visfatin and metallothionein-2.
  
  
  
  This study has identified two panels of candidate biomarkers for the diagnosis of IBD and the differentiation of IBD subtypes to guide appropriate therapeutic interventions in paediatric patients.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Starr
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Deeke
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Cheng-Kang
authors.initials: CK
authors.lastname: Chiang
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.|Department of Microbiology and Immunology, Mansoura University, Mansoura, Egypt.
authors.forename: Walid
authors.initials: W
authors.lastname: Mottawea
authors.affiliation: Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Ruth
authors.initials: R
authors.lastname: Singleton
authors.affiliation: Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada.|Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.|School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Eric I
authors.initials: EI
authors.lastname: Benchimol
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Ming
authors.initials: M
authors.lastname: Wen
authors.affiliation: Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada.|Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: Mack
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Stintzi
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.|Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Figeys
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy / Q000379:methods; D002170:Canada; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D044682:Colon, Ascending / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D061345:Early Medical Intervention; D005260:Female; D006801:Humans; D008297:Male; D063993:Mitochondrial Trifunctional Protein, beta Subunit / Q000032:analysis*; D054409:Nicotinamide Phosphoribosyltransferase / Q000032:analysis*; D018579:Patient Selection; D040901:Proteomics / Q000379:methods*
chemical_list: D015415:Biomarkers; D063993:Mitochondrial Trifunctional Protein, beta Subunit; D054409:Nicotinamide Phosphoribosyltransferase
keywords: CROHN'S DISEASE; IBD; IBD BASIC RESEARCH; ULCERATIVE COLITIS