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Plasma glycoproteomics delivers high-specificity disease biomarkers by detecting site-specific glycosylation abnormalities

ABSTRACT: The human plasma glycoproteome holds enormous potential to identify personalized biomarkers to diagnose and understand disease. Recent advances in mass spectrometry and software development are opening novel avenues to mine the glycoproteome for protein- and site-specific glycosylation changes. Here, we describe a novel plasma N-glycoproteomics method for disease diagnosis and evaluated its clinical applicability by performing comparative glycoproteomics in blood plasma of 40 controls and a cohort of 74 patients with 13 different genetic diseases that directly impact the protein N-glycosylation pathway. The plasma glycoproteome yielded high-specificity biomarker signatures for each of the individual genetic defects. Bioinformatic analyses revealed site-specific glycosylation differences that could be explained by underlying glycobiology and in specific diseases by protein-intrinsic factors. Our work illustrates the strong potential of plasma glycoproteomics to significantly increase specificity of glycoprotein biomarkers with direct insights in site-specific glycosylation changes to better understand the mechanisms underlying human disease.

INSTRUMENT(S): maXis

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Congenital Disorder Of Glycosylation

SUBMITTER: Hans Wessels

LAB HEAD: Alain J van Gool

PROVIDER: PXD034214 | Pride | 2022-06-01

REPOSITORIES: Pride

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