A site-specific map of the human plasma glycome and its age and gender-associated alterations
Open accessAbstract
Alterations in the human glycome have been associated with cancer and autoimmunity. Thus, constructing a site-specific map of the human glycome for biomarker research and discovery has been a highly sought-after objective. However, due to analytical barriers, comprehensive site-specific glycoprofiling is difficult to perform. To develop a platform to detect easily quantifiable, site-specific, disease-associated glycan alterations for clinical applications, we have adapted the multiple reaction monitoring mass spectrometry method for use in glycan biomarker research. The adaptations allow for highly precise site-specific glycan monitoring with minimum sample prep. Using this technique, we successfully mapped out the relative abundances of the most common 159 glycopeptides in the plasma of 97 healthy volunteers. This plasma glycome map revealed 796 significant (FDR < 0.05) site-specific inter-protein and intra-protein glycan associations, of which the vast majority were previously unknown. Since age and gender are relevant covariants in biomarker research, these variables were also characterized. 13 glycopeptides were found to be associated with gender and 41 to be associated with age. Using just five age-associated glycopeptides, a highly accurate age prediction model was constructed and validated (r 2 = 0.62 ± 0.12). The human plasma site-specific glycan map described herein has utility in applications ranging from glycan biomarker research and discovery to the development of novel glycan-altering interventions.
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Recent mass spectrometry studies examining the concentrations of just a few well-studied glycans have been able to accurately predict chronological age and ageing phenotypes.
“Although it is not yet possible to comprehensively survey the glycome, recent mass spectrometry studies examining the concentrations of just a few well-studied glycans have been able to accurately predict chronological age and ageing phenotypes.”
From Measuring biological age using omics data (2022) · cites this paper as [130]
Merleev et al. used mass spectrometry to examine the concentration of 159 glycans on 17 common glycoproteins in plasma, which showed promise as an ageing clock, although results were not validated in an independent cohort nor associated with any ageing phenotypes.
“Merleev et al.130 used mass spectrometry methods to examine the concentration of 159 glycans on 17 common glycoproteins in plasma, which also showed promise as an ageing clock, although results were not validated in an independent cohort nor associated with any ageing phenotypes.”
From Measuring biological age using omics data (2022) · cites this paper as [130]
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- Authors
- Merleev, A. A., Park, D., Xie, Y., Kailemia, M. J., Xu, G., Ruhaak, L. R., Kim, K., Hong, Q., Li, Q., Patel, F., Wan, Y.-J. Y., Marusina, A. I., Adamopoulos, I. E., Lal, N. N., Mitra, A., Le, S. T., Shimoda, M., Luxardi, G., Lebrilla, C. B., & Maverakis, E.
- Affiliations
- University of California Davis Medical Center (US)
- Beth Israel Deaconess Medical Center (US)
- University of California, Davis (US)
- Leiden University Medical Center (NL)
- Shriners Hospitals for Children - Northern California (US)
- Corresponding author
- Lebrilla, Carlito B.
- Maverakis, Emanual
- ORCID
- Venue
- Scientific Reports
- Published
- 2020-10-15
- Volume
- 10
- Issue
- 1
- Pages
- 17505-17505
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7567094
- OpenAlex
- W3092933954
- Cited by
- 17
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute (Physician-Scientist Early Career Award)
- Burroughs Wellcome Fund (Career Awards for Medical Scientists (CAMS))
- Martin and Dorothy Charitable Spatz Foundation (Cutaneous T Cell Lymphoma Pilot Award)
- National Institutes of Health (DP2OD008752)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- glycopeptides, glycan biomarkers, age prediction, glycoproteomics
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Blood Proteins, Female, Glycopeptides, Glycosylation, Humans, Immunoglobulin G, Male, Middle Aged, Polysaccharides, Sex Factors, Biomarkers, Likelihood Functions, Spectrometry, Mass, Electrospray Ionization, Glycomics, Young Adult, Healthy Volunteers
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