Glycoinformatic profiling of label-free intact heparan sulfate oligosaccharides

Heparan sulfates (HS) are a group of heterogenous linear, sulfated polysaccharides that play a role in in health and many diseases including cancer, cardiovascular, and kidney diseases. The structural variety of HS has greatly challenged the development and utility of HS analytics, particularly for native structures, leaving a significant gap in HS technologies for clinical application. Mass spectrometry (MS)-based profiling with bioinformatics offers a top-down approach that can retain variety in large data sets. Using healthy human plasmas, we developed an MS glycoprofiling approach for native HS oligosaccharides, which retains the structural complexity of each individual HS chain and generates an HS index (or Heparan-ome) for each patient. As a proof of concept, analysis of 56 plasma samples ranging from 6 groups of kidney disease patients revealed a new subset cluster (20%, 4/20) of membranous glomerulopathy (MG) patients with distinct HS profiles, highlighting the potential of HS glycoprofiling as a powerful new approach into clinical practice, which warrants future development into clinical diagnostics of kidney and other diseases.