image: Schematic overview of the GlycoHBF workflow, from collection of 15 body fluid types to standardized processing and dual-layer proteomic and glycoproteomic profiling.
Credit: Yong Zhang
Proteins in human body fluids are a goldmine of information for understanding health and detecting disease. However, proteins are often decorated with complex sugar chains called glycans, a modification known as glycosylation, which fine-tunes their function and can signal the onset of conditions like cancer or autoimmune disorders. While blood and urine are routinely analyzed, a systematic and comparable map of the protein and glycosylation landscape across a wide variety of clinically relevant body fluids has been missing.
To bridge this gap, a team led by Dr. Yong Zhang at West China Hospital, Sichuan University, created the GlycoHBF dataset. The team collected and analyzed 15 different types of human body fluids, including plasma, urine, cerebrospinal fluid, saliva, tears, sweat, bile, and even synovial fluid from joints. Notably, the team developed and applied a uniform, standardized workflow for all sample types, from collection and preparation to analysis using state-of-the-art mass spectrometry (LC-MS/MS).
The team identified and quantified thousands of proteins and intact N-glycopeptides. While some proteins are shared across all fluids, each body fluid possesses a unique molecular signature. The differences in glycosylation patterns between fluids were even more pronounced than the differences in protein levels alone. This suggests that glycosylation offer an extra layer of diagnostic specificity that may be more sensitive to local tissue environments.
The findings are published in Glycoscience & Therapy.
Novelty: Unlike previous studies that focused on a single body fluid or used varied methods, GlycoHBF is the first resource to provide a direct, parallel comparison of both proteomic and N-glycoproteomic profiles across 15 distinct human body fluids using a strictly standardized protocol. By employing advanced DIA mass spectrometry for proteins and a combined EThcD-sceHCD fragmentation method for glycopeptides, the study achieves exceptional depth and reproducibility. The resulting dataset, publicly available via iProX (PXD068799), establishes a new benchmark for reproducibility and provides a crucial reference framework for the research community.
Significance: This study lays a foundation for the future of liquid biopsies. By establishing the baseline molecular profiles of healthy and non-malignant body fluids, GlycoHBF better differentiation between normal physiological variation and pathological changes associated with diseases. The standardized methods provided in the study can be directly adopted by clinical researchers to ensure consistent and comparable results across large patient cohorts. Ultimately, this atlas will help accelerate the identification of specific protein or glycopeptide signatures that could serve as early warning signs for diseases affecting the brain (via cerebrospinal fluid), lungs (via pleural fluid), kidneys (via urine), or joints (via synovial fluid), advancing the field of precision medicine.
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Contact the author: Yong Zhang, Department of Thyroid Surgery, Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, PR China, nankai1989@foxmail.com
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Journal
Glycoscience & Therapy
Method of Research
Experimental study
Subject of Research
Human tissue samples
Article Title
GlycoHBF: Mass spectrometry-based glycoproteomics data from 15 types of human body fluids
COI Statement
Yong Zhang is a guest editor for Glycoscience & Therapy and was not involved in the editorial review or the decision to publish this article. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.