Biology subjects

Lageveen-Kammeijer, G. S. M.

Publications and source records attributed to Lageveen-Kammeijer, G. S. M..

3 recordsLinked to original sources

bioRxiv2025

Decoding the Glycan Signature: Unraveling N-Glycosylation Alterations in Glycogen Storage Disease Ia and Ib

Glycogen storage disease (GSD) types Ia and Ib are rare inherited metabolic disorders caused by pathogenic variants in G6PC or SLC37A4, respectively. These defects disrupt glucose homeostasis and may affect protein glycosylation. We systematically profiled sera N-glycomes from retrospectively collected GSD Ia (n=17), GSD Ib (n=8), and control (n=21) samples. Derived traits analyses revealed distinct, subtype-specific, and shared glycomic alterations, including shifts from 2,3-to 2,6-sialylation in both subtypes. GSD Ia showed enhanced branching and reduced fucosylation, whereas GSD Ib displayed elevated fucosylation, bisection, and reduced branching. In GSD Ia patients with hepatocellular adenoma/carcinoma (HCA/HCC), further enrichment of oligomannosidic and 2,3-sialylation was observed. Several individual N-glycans showed strong discriminatory performance, supporting their potential as biomarkers for GSD I subtyping and HCA/HCC surveillance. This study provides the first comprehensive characterization of systemic N-glycans in GSD Ia and Ib, revealing glycomic remodeling as a potential biomarker of disease subtypes and tumor progression. Take-home message (synopsis) of the articleSerum/plasma N-glycomic profiling reveals distinct glycosylation signatures in GSD Ia and GSD Ib, including tumor-associated shifts in GSD Ia, highlighting novel biomarkers for disease subtyping and surveillance of hepatic complications.

biochemistry↗

bioRxiv2025

Employing neutron-encoded monoUbs to study E2/E3 ligase activity and selectivity for assembling Ub chains

While protein ubiquitination is an extensively studied post-translational modification, many aspects of this process remain unclear. Ubiquitin conjugation involves the action of three different types of enzymes working in concert to install ubiquitin onto substrate proteins. Despite efforts, an in vitro mid/high-throughput screen to quickly determine which enzymes work together to build ubiquitin chains and directly analyze the type(s) of chains formed does not exist. In this study, we developed a new multiplexed mass spectrometry-based E1-E2-E3 assay that enables the analysis of whether E2/E3 pairs work together to form ubiquitin chains and concomitantly reports on the nature of the formed ubiquitin chain type(s). The assay employs synthetic modified neutron-encoded monoUb substrates with a distinct molecular weight, enabling the simultaneous analysis of these substrates. Overall, various E2-E3 pairs were screened for their ability to build Ub chains, which furnished a three-dimensional overview of linkage selectivity over time and enzyme concentration. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/655449v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@130203aorg.highwire.dtl.DTLVardef@93c9adorg.highwire.dtl.DTLVardef@9d9bedorg.highwire.dtl.DTLVardef@167ea0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

GlycoGenius: the ultimate high-throughput glycan composition identification tool

Mass spectrometry is recognized as the gold standard for glycan analysis, yet the complexity of generated data hampers progress in glycobiology, as existing tools lack full automation, requiring extensive manual effort. We introduce GlycoGenius, an open-source program offering an automated workflow for glycomics data analysis, featuring an intuitive graphical interface. With algorithms tailored to reduce manual workload, it allows for data visualization and automatically constructs search spaces, identifies, scores, and quantifies glycans, filters results, and annotates fragment spectra of N- and O-glycans, glycosaminoglycans and more. It seamlessly guides researchers of all expertise levels from raw data to publication-ready figures. Our findings demonstrate that GlycoGenius achieves results comparable with manual analysis or competing tools, identifying more glycans, including novel ones, while significantly reducing processing time. This groundbreaking tool represents a significant advancement in the study of glycoconjugates, empowering researchers to focus on insights rather than data processing.

bioinformatics↗