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Reproducible determination of HDL proteotypes

ABSTRACT: High-density lipoprotein (HDL) is a heterogenous mixture of blood-circulating multimolecular particles containing many different proteins, lipids, and RNAs. Recent advancements in Mass spectrometry-based proteotype analysis enables the sensitive and reproducible quantification of proteoforms across large patient cohorts. To create spectral libraries enabling data-independent acquisition (DIA) strategies HDL was isolated from plasma of more than 300 patients with a multiplicity of physiological HDL states. HDL proteome spectral libraries consisting of 296 protein groups and 341 peptidoforms of potential biological relevance were established and used to evaluate HDL proteotype differences in between healthy individuals and patients suffering from diabetes mellitus type 2 and/or coronary heart disease. Bioinformatic interrogation of the data revealed quantitative differences in the patient-derived HDL proteotypes including a depletion of phosphatidylinositol-glycan-specific phospholipase D (PHLD) from disease-derived HDL particles. The DIA-based HDL proteotyping strategy enables the digitization of HDL proteotypes derived from heterogenous patient cohorts and provides insights into the composition of HDL particles as a rational basis to decode HDL structure-function-disease relationships.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Bernd Wollscheid

PROVIDER: MSV000084733 | MassIVE | Sat Dec 21 16:01:00 GMT 2019

REPOSITORIES: MassIVE

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