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Ultradeep N-glycoproteome Atlas of Mouse Reveals Spatiotemporal Signatures of Brain Aging and Neurodegenerative Diseases
Open accessPreprint — published as 10.1038/s41467-025-60437-6
Abstract
The current depth of site-specific N-glycoproteomics is insufficient to fully characterize glycosylation events in biological samples. Herein, we achieved an ultradeep and precision analysis of the N-glycoproteome of mouse tissues by integrating multiple workflows. The largest N-glycoproteomic dataset to date was established on mice, which contained 91,972 precursor glycopeptides, 62,216 glycoforms, 8,939 glycosites and 4,563 glycoproteins. The database consisted of 6.8 million glyco-spectra (containing oxonium ions), among which 160,928 were high-quality spectra with confident N-glycopeptide identifications. The large-scale and high-quality dataset enhanced the performance of current artificial intelligence models for glycopeptide tandem spectrum prediction. Using this ultradeep dataset, we observed tissue specific microheterogeneity and functional implications of protein glycosylation in mice. Furthermore, the region-resolved brain N-glycoproteomes for Alzheimer’s Diseases, Parkinson Disease and aging mice revealed the spatiotemporal signatures and distinct pathological functions of the N-glycoproteins. A comprehensive database resource of experimental N-glycoproteomic data from this study and previous literatures were further established. This N-glycoproteome atlas serves as a promising tool for revealing the role of protein glycosylation in biological systems.
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Metadata
- Authors
- Fang, P., Yu, X., Ding, M., Cong, Q., Jiang, H., Shi, Q., Zhao, W., Zheng, W., Li, Y., Ling, Z., Kong, W.-J., Yang, P., & Shen, H.
- Affiliations
- Soochow University (CN)
- Shanghai Medical College of Fudan University (CN)
- Second Affiliated Hospital of Soochow University (CN)
- The Affiliated Taizhou People's Hospital of Nanjing Medical University (CN)
- Tongji University (CN)
- Fudan University (CN)
- Corresponding author
- Fang, Pan
- Shen, Huali
- ORCID
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2025-02-19
- Volume
- 16
- Issue
- 1
- Pages
- 5568-5568
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC12215503
- OpenAlex
- W4411887142
- Cited by
- 13
- References
- 1
- Citations by year
- 2026: 7 · 2025: 6
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.biorxiv.org/about/FAQ#license (vor)
- Locations
- Nature Communications (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81827901, 32200778, 22201217, 82272174, 62475179, 32101026, 2022ZD0211600, 32471014)
- Government of Jiangsu Province
- Science and Technology Commission of Shanghai Municipality (22S31901900)
- Ministry of Education, India
- Natural Science Foundation of Jiangsu Province (BK20220494)
- Soochow University
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- National Key Research and Development Program of China (2021YFA1301601, 2022YFC2503904)
- Second Affiliated Hospital of Soochow University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- N-glycoproteome, protein glycosylation, mouse tissues, brain aging, Alzheimer's disease, Parkinson's disease, neurodegenerative diseases, glycopeptide identification, glycoforms
- MeSH terms
- Aging, Alzheimer Disease, Animals, Brain, Glycopeptides, Glycoproteins, Glycosylation, Humans, Male, Mice, Inbred C57BL, Parkinson Disease, Neurodegenerative Diseases, Proteome, Databases, Protein, Proteomics, Mice
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