Glycoinformatic Profiling of Label-Free Intact Heparan Sulfate Oligosaccharides

Area of Science:

• Biochemistry
• Glycobiology
• Proteomics

Background:

• Heparan sulfates (HS) are structurally diverse sulfated polysaccharides crucial in various physiological and pathological processes, including cancer, cardiovascular, and kidney diseases.
• The heterogeneity of HS structures presents significant challenges for analytical methods, hindering clinical applications.
• Existing analytical techniques often struggle to capture the complexity of native HS structures.

Purpose of the Study:

• To develop a mass spectrometry (MS)-based glycoprofiling approach for analyzing native HS oligosaccharides in human plasma.
• To establish an HS 'index' (Heparan-ome) for individual patients, preserving structural complexity.
• To demonstrate the potential of HS glycoprofiling for clinical diagnostics, particularly in kidney diseases.

Main Methods:

• Development of an MS-based glycoprofiling strategy for native HS oligosaccharides.
• Application of bioinformatics for data analysis and generation of an HS 'index' or Heparan-ome.
• Analysis of 53 plasma samples from healthy individuals and four groups of kidney disease patients.

Main Results:

• Successful development of an MS glycoprofiling approach for native HS oligosaccharides.
• Generation of patient-specific HS 'indices' (Heparan-omes).
• Identification of a distinct HS profile subset in 21% of membranous glomerulopathy (MG) patients, differentiating them from other kidney disease groups.

Conclusions:

• HS glycoprofiling is a powerful approach for retaining structural complexity and holds significant potential for clinical applications.
• Distinct HS profiles can serve as biomarkers for specific kidney diseases, such as membranous glomerulopathy.
• Further development into quantitative oliGAGomics and clinical diagnostics for kidney and other diseases is warranted.