Oxonium ion scanning mass spectrometry for large-scale plasma glycoproteomics
Matthew White, Ludwig Sinn, D. Marc Jones, Joost de Folter, Simran Kaur Aulakh, Ziyue Wang, Helen R. Flynn, Lynn Krüger, Pinkus Tober‐Lau, Vadim Demichev, Florian Kurth, Michael Mülleder, Véronique Blanchard, Christoph B. Messner, Markus Ralser
Abstract
Protein glycosylation, a complex and heterogeneous post-translational modification that is frequently dysregulated in disease, has been difficult to analyse at scale. Here we report a data-independent acquisition technique for the large-scale mass-spectrometric quantification of glycopeptides in plasma samples. The technique, which we named 'OxoScan-MS', identifies oxonium ions as glycopeptide fragments and exploits a sliding-quadrupole dimension to generate comprehensive and untargeted oxonium ion maps of precursor masses assigned to fragment ions from non-enriched plasma samples. By applying OxoScan-MS to quantify 1,002 glycopeptide features in the plasma glycoproteomes from patients with COVID-19 and healthy controls, we found that severe COVID-19 induces differential glycosylation in IgA, haptoglobin, transferrin and other disease-relevant plasma glycoproteins. OxoScan-MS may allow for the quantitative mapping of glycoproteomes at the scale of hundreds to thousands of samples.