Finding Unanticipated Modifications to N-Glycans in Glycoproteomics Data

CSEF · 2026 Biochemistry/ Molecular Biology (Senior Division)

Overview

Protein glycosylation is a highly diverse and complex post-translational modification that is critical to many biological processes, such as intercellular communication and protein folding. Glycoproteins are frequently studied using mass spectrometry, and successful data interpretation using database search requires a complete protein database—a condition that is frequently satisfied—as well as a complete glycan database—a condition that is often not satisfied. The goals of this project are to: (1) develop software that helps build improved N-glycan databases by performing a sample-specific analysis of the mass spectrometry data to look for unanticipated modifications to N-linked glycans, and (2) use the software to discover unanticipated modifications in mass spectrometry data that has been deposited in public mass spectrometry data repositories, such as PRIDE (https://www.ebi.ac.uk/pride/) and MassIVE (https://massive.ucsd.edu/). This project builds on top of the GlycoNetworks software (https://doi.org/10.1021/acs.jproteome.5c00006). GlycoNetworks uses building blocks specified in advance by the user to construct glycan networks and then analyzes individual networks to build improved N-glycan databases. My software enhances GlycoNetworks to find building blocks of arbitrary mass (i.e., unanticipated modifications) by looking for masses that are unusually effective at connecting different networks. Examples of unanticipated building block masses that I found in PRIDE and MassIVE datasets include 28 Da (which can be ascribed to formylation, an undesirable sample prep artifact that can occur when samples are stored in formic acid), 165 Da (which can be explained as phosphorylcholine, a building block that is known to occur in insects), and 114 Da (still unexplained). Furthermore, my software can identify the mass with high accuracy and precision and can thus distinguish modifications of nearly identical mass—for example, phosphorylation (79.966 Da) vs sulfation (79.957 Da).

Competition history

  • CSEF 2026 Biochemistry/ Molecular Biology (Senior Division) · Entry S-04-19

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