Dataset Information

Ultradeep N-glycoproteome Atlas of Mouse Reveals Spatiotemporal Signatures of Brain Aging and Neurodegenerative Diseases

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.

ORGANISM(S): Mus Musculus

SUBMITTER: Pan Fang

PROVIDER: PXD061436 | iProX | Tue Mar 04 00:00:00 GMT 2025

REPOSITORIES: iProX

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Ultradeep N-glycoproteome atlas of mouse reveals spatiotemporal signatures of brain aging and neurodegenerative diseases.

Fang Pan P Yu Xiangming X Ding MengYang M Qifei Cong C Jiang Hongyu H Shi Qi Q Zhao Weiwei W Zheng Weimin W Li Yingning Y Ling Zixiang Z Kong Wei-Jun WJ Yang Pengyuan P Shen Huali H

Nature communications 20250701 1

The current depth of site-specific N-glycoproteomics is insufficient to fully characterize glycosylation events in biological samples. Herein, we achieve an ultradeep and precision analysis of the N-glycoproteome of mouse tissues by integrating multiple workflows. The largest N-glycoproteomic dataset to date is established on mice, which contains 91,972 precursor glycopeptides, 62,216 glycoforms, 8939 glycosites and 4563 glycoproteins. The database consists of 6.8 million glyco-spectra (containi ...[more]

PMID: 40593524

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Project description:Site-specific O-glycoproteome mapping in complex biological system provides molecular basis for understanding the structure-function relationships of glycoproteins and their roles in physiological and pathological processes. Previous O-glycoproteome analysis in cerebrospinal fluid (CSF) focused on sialylated glycoforms, and many CSF glycoproteins have not been characterized comprehensively with respect to their O-glycosylation. In order to provide an unbiased O-glycosylation profiling, we have developed an integrated strategy combining universal boronic acid enrichment, high-pH fractionation, and electron-transfer and higher-energy collision dissociation (EThcD) for improved intact O-glycopeptide analysis. This strategy was applied to analyze O-glycoproteome in CSF, leading to identifications of 308 O-glycopeptides from 110 O-glycoproteins, covering both sialylated and non-sialylated glycoforms. To our knowledge, this is the largest number of O-glycoproteins and O-glycosites reported for CSF so far, including 154 novel O-glycosites. Due to a lack of peptidomics workflow that could incorporate glycosylation analysis, the glycosylation state of CSF endogenous peptides has not been comprehensively studied. Here, we developed a peptidomics workflow that utilizes the EThcD fragmentation and a three-step database searching strategy, allowing both N-glycosylation and O-glycosylation, as well as other common peptide PTMs, to be analyzed at the same time. Interestingly, among the 1492 endogenous peptides identified, 95 of them were O-glycosylated and only 1 N-glycosylated peptide was found, indicating CSF endogenous peptides were preferentially O-glycosylated. By referring to human neuropeptide database, 15 of them were actually O-glycosylated neuropeptides deriving from ProSAAS and secretogranin-1. O-glycoproteome and endogenous peptidome PTMs analysis were also conducted in MCI and AD patients to give a landscape picture of glycosylation in these disease states. The results showed that a decreased fucosylation trend was found in MCI and AD, suggesting its potential relation to the progression of AD.

Dataset Information

Ultradeep N-glycoproteome Atlas of Mouse Reveals Spatiotemporal Signatures of Brain Aging and Neurodegenerative Diseases

Publications

Ultradeep N-glycoproteome atlas of mouse reveals spatiotemporal signatures of brain aging and neurodegenerative diseases.

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