title: In-Depth Cerebrospinal Fluid Quantitative Proteome and Deglycoproteome Analysis: Presenting a Comprehensive Picture of Pathways and Processes Affected by Multiple Sclerosis.
abstract: In the current study, we conducted a quantitative in-depth proteome and deglycoproteome analysis of cerebrospinal fluid (CSF) from relapsing-remitting multiple sclerosis (RRMS) and neurological controls using mass spectrometry and pathway analysis. More than 2000 proteins and 1700 deglycopeptides were quantified, with 484 proteins and 180 deglycopeptides significantly changed between pools of RRMS and pools of controls. Approximately 300 of the significantly changed proteins were assigned to various biological processes including inflammation, extracellular matrix organization, cell adhesion, immune response, and neuron development. Ninety-six significantly changed deglycopeptides mapped to proteins that were not found changed in the global protein study. In addition, four mapped to the proteins oligo-myelin glycoprotein and noelin, which were found oppositely changed in the global study. Both are ligands to the nogo receptor, and the glycosylation of these proteins appears to be affected by RRMS. Our study gives the most extensive overview of the RRMS affected processes observed from the CSF proteome to date, and the list of differential proteins will have great value for selection of biomarker candidates for further verification.
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, ‡The KG Jebsen Centre for MS Research, Department of Clinical Medicine, §KG Jebsen Center for Diabetes Research, Department of Clinical Science, and ⊥Computational Biology Unit, Department of Informatics, University of Bergen , Bergen N-5009, Norway.|Center for Medical Genetics and Molecular Medicine and ∥The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital , Bergen N-5021, Norway.
authors.forename: Ann Cathrine
authors.initials: AC
authors.lastname: Kroksveen
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, ‡The KG Jebsen Centre for MS Research, Department of Clinical Medicine, §KG Jebsen Center for Diabetes Research, Department of Clinical Science, and ⊥Computational Biology Unit, Department of Informatics, University of Bergen , Bergen N-5009, Norway.|Center for Medical Genetics and Molecular Medicine and ∥The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital , Bergen N-5021, Norway.
authors.forename: Astrid
authors.initials: A
authors.lastname: Guldbrandsen
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, ‡The KG Jebsen Centre for MS Research, Department of Clinical Medicine, §KG Jebsen Center for Diabetes Research, Department of Clinical Science, and ⊥Computational Biology Unit, Department of Informatics, University of Bergen , Bergen N-5009, Norway.|Center for Medical Genetics and Molecular Medicine and ∥The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital , Bergen N-5021, Norway.
authors.forename: Marc
authors.initials: M
authors.lastname: Vaudel
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, ‡The KG Jebsen Centre for MS Research, Department of Clinical Medicine, §KG Jebsen Center for Diabetes Research, Department of Clinical Science, and ⊥Computational Biology Unit, Department of Informatics, University of Bergen , Bergen N-5009, Norway.|Center for Medical Genetics and Molecular Medicine and ∥The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital , Bergen N-5021, Norway.
authors.forename: Ragnhild Reehorst
authors.initials: RR
authors.lastname: Lereim
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, ‡The KG Jebsen Centre for MS Research, Department of Clinical Medicine, §KG Jebsen Center for Diabetes Research, Department of Clinical Science, and ⊥Computational Biology Unit, Department of Informatics, University of Bergen , Bergen N-5009, Norway.|Center for Medical Genetics and Molecular Medicine and ∥The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital , Bergen N-5021, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Barsnes
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, ‡The KG Jebsen Centre for MS Research, Department of Clinical Medicine, §KG Jebsen Center for Diabetes Research, Department of Clinical Science, and ⊥Computational Biology Unit, Department of Informatics, University of Bergen , Bergen N-5009, Norway.|Center for Medical Genetics and Molecular Medicine and ∥The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital , Bergen N-5021, Norway.
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, ‡The KG Jebsen Centre for MS Research, Department of Clinical Medicine, §KG Jebsen Center for Diabetes Research, Department of Clinical Science, and ⊥Computational Biology Unit, Department of Informatics, University of Bergen , Bergen N-5009, Norway.|Center for Medical Genetics and Molecular Medicine and ∥The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital , Bergen N-5021, Norway.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Torkildsen
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, ‡The KG Jebsen Centre for MS Research, Department of Clinical Medicine, §KG Jebsen Center for Diabetes Research, Department of Clinical Science, and ⊥Computational Biology Unit, Department of Informatics, University of Bergen , Bergen N-5009, Norway.|Center for Medical Genetics and Molecular Medicine and ∥The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital , Bergen N-5021, Norway.
authors.forename: Frode S
authors.initials: FS
authors.lastname: Berven
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D002448:Cell Adhesion; D002556:Cerebrospinal Fluid Proteins / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000276:immunology; D005109:Extracellular Matrix / Q000235:genetics* / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000134:cerebrospinal fluid / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006023:Glycoproteins / Q000134:cerebrospinal fluid / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000276:immunology; D055495:Neurogenesis / Q000235:genetics / Q000276:immunology; D000070816:Nogo Receptor 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D025941:Protein Interaction Mapping; D020543:Proteome / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D000070816:Nogo Receptor 1; D020543:Proteome; C486580:RTN4R protein, human; C081451:olfactomedin
keywords: TMT; biomarkers; cerebrospinal fluid; glycosylation; immune system; inflammation; multiple sclerosis; neuron development; protein networks