MassIVE MSV000094307

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Multi-omics discovery of hallmark protein and lipid features of circulating small extracellular vesicles in humans

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Description

Extracellular vesicles (EVs) are now being increasingly recognized as an essential signalling entity in human plasma, linking them to health and various diseases. Still, their core protein and lipid componentry, which epicentres EV form and function, remains poorly defined. Achieving this unmet milestone remains greatly hindered by abundant non-vesicular extracellular plasma components (non-EVs) in mass spectrometry-based analyses. Here, we performed high-resolution density gradient fractionation of over 80 human plasma samples to isolate circulating EVs, and systematically construct their quantitative proteome (4500 proteins) and lipidome (829 lipids) landscapes. This led to the discovery of a highly conserved panel of 182 proteins (ADAM10, STEAP23, STX7) and 52 lipids (PS, PIPs, Hex2Cer, PAs), providing a deep survey of hallmark molecular features and biological pathways intrinsic to circulating EVs. Our efforts also mapped the surfaceome diversity, identifying 126 proteins on EV surface. We further establish a set of 42 proteins and 114 lipids features that served as hallmark features of non-EV particles in plasma. We submit ADAM10 and PS(36:1) as conserved EV biological markers that enable precise differentiation between EV and non-EV particles. Our findings, which can be explored via open-source Shiny web tool will serve as a valuable repository to the research community for a clearer understanding of circulating EV biology. [doi:10.25345/C5R20S72N] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: extracellular vesicle ; circulating EV ; plasma ; proteomics ; lipidomics ; repository

Contact

Principal Investigators:
(in alphabetical order) 		David Greening, Baker Heart & Diabetes Institute, Australia
Submitting User: dwgree
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Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

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Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
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