Serum N-Glycosylation in Parkinson's Disease: A Novel Approach for Potential Alterations

• Published in: Molecules (Basel, Switzerland) Switzerland), 2019-06, Vol.24 (12), p.2220
• Main Authors: Váradi, Csaba, Nehéz, Károly, Hornyák, Olivér, Viskolcz, Béla, Bones, Jonathan
• Format: Article
• Language: English
• Subjects: Algorithms; Capillaries; capillary electrophoresis; Classification; Conditioning; Digestion; Disease; Electrolytes; Electroosmosis; Electrophoresis, Capillary; Flow stability; Glycosylation; Humans; Identification; label-free quantitation; Males; Parkinson Disease - metabolism; Parkinson's disease; Polyethylene; Polyethylene oxide; Silica; Support Vector Machine; Support vector machines; Tandem Mass Spectrometry
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24122220

In this study, we present the application of a novel capillary electrophoresis (CE) method in combination with label-free quantitation and support vector machine-based feature selection (support vector machine-estimated recursive feature elimination or SVM-RFE) to identify potential glycan alterations in Parkinson's disease. Specific focus was placed on the use of neutral coated capillaries, by a dynamic capillary coating strategy, to ensure stable and repeatable separations without the need of non-mass spectrometry (MS) friendly additives within the separation electrolyte. The developed online dynamic coating strategy was applied to identify serum N-glycosylation by CE-MS/MS in combination with exoglycosidase sequencing. The annotated structures were quantified in 15 controls and 15 Parkinson's disease patients by label-free quantitation. Lower sialylation and increased fucosylation were found in Parkinson's disease patients on tri-antennary glycans with 2 and 3 terminal sialic acids. The set of potential glycan alterations was narrowed by a recursive feature elimination algorithm resulting in the efficient classification of male patients.