The Francis Crick Institute
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Oxonium ion scanning mass spectrometry for large-scale plasma glycoproteomics.

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journal contribution
posted on 2024-04-11, 09:39 authored by Matthew EH White, Ludwig R 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
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.


Crick (Grant ID: CC1119, Grant title: STP Scientific Computing) Crick (Grant ID: CC1063, Grant title: STP Proteomics) Crick (Grant ID: 10134, Grant title: Ralser FC001134) Wellcome Trust (Grant ID: 200829/Z/16/Z, Grant title: WT 200829/Z/16/Z)