Glycosphingolipids (GSLs) are important targets in immune, infectious, lysosomal storage diseases, cancer, and neurodegenerative diseases. Circulatory GSL profiling in clinical samples is restricted by the lack of mid- and high-throughput analytical methods and deep coverage of long-chain sialylated glycosphingolipidome.
We present a 4-dimensional (4D)-glycosphingolipidomics platform for routine glycosphingolipidome profiling encompassing: extraction and fractionation of sialylated GSLs with 3 to 15 monosaccharides, neutral GSLs and sulfatides; µL-flow reversed-phase LC-TIMS-PASEF MS analysis; semi-quantification strategy adapted for fractionated glycosphingolipidome, and referential CCS, RT, and m/z values for GSL annotation. 4D-glycosphingolipidomics of human serum reveals a high structural heterogeneity, amounting to 376 GSLs: 159 GSLs of ganglio- and neolacto-series, 145 neutral GSLs and 72 sulfatides.
Here we demonstrate the platform’s utility for clinical profiling of Parkinson’s disease (PD) sera. 41 neolacto- and ganglio-species discriminate PD patients from controls and 14 GSLs differentiate sex subgroups, laying the foundation for further functional GSL studies with PD.
[doi:10.25345/C53J39C93]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: lipidomics ; glycosphingolipids ; TIMS PASEF ; ion mobility mass spectrometry ; DatasetType:Other (Lipidomics)
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Principal Investigators: (in alphabetical order) |
Laura Bindila, Clinical Lipidomics Unit, Institute of Physiological Chemistry, University Medical Center Mainz, Germany |
| Submitting User: | huovo |
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