Published November 28, 2023
| Version v1
Journal article
Open
A proteomic meta-analysis refinement of plasma extracellular vesicles
Creators
- 1. Brigham Young University
- 2. Pacific Northwest National Laboratory
- 3. University of Chicago
- 4. University of Alabama at Birmingham
- 5. Indiana University
Description
Extracellular vesicles play major roles in cell-to-cell communication and are excellent biomarker candidates. However, studying plasma extracellular vesicles is challenging due to contaminants. Here, we performed a proteomics meta-analysis of public data to refine the plasma EV composition by separating EV proteins and contaminants into different clusters. We obtained two clusters with a total of 1717 proteins that were depleted of known contaminants and enriched in EV markers with independently validated 71% true-positive. These clusters had 133 clusters of differentiation (CD) antigens and were enriched with proteins from cell-to-cell communication and signaling. We compared our data with the proteins deposited in PeptideAtlas, making our refined EV protein list a resource for mechanistic and biomarker studies. As a use case example for this resource, we validated the type 1 diabetes biomarker proplatelet basic protein in EVs and showed that it regulates apoptosis of β cells and macrophages, two key players in the disease development. Our approach provides a refinement of the EV composition and a resource for the scientific community.
Data availability
Additional data are available in Open Science Framework (https://doi.org/10.17605/OSF.IO/2UQPK). This includes MaxQuant results and parameter files for each dataset under the folder "MaxQuant_results_and_parameters", which are named based on their Pride accession numbers; an excel file containing the complete abundance data matrix under the folder "Processed_data_matrix"; and the results from the DAVID functional enrichment analysis under the folder "Enrichment analyses".
The R and Python scripts written to generate Fig. 5 and Figure S2 are available in GitHub (https://doi.org/10.5281/zenodo.10079817).
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Proteomic-meta-analysis-refinement-of-plasma-extracellular-vesicles.pdf
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Additional details
Identifiers
- DOI
- 10.1038/s41597-023-02748-1
- Other
- oai:uchicago.tind.io:10033
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases
- U01 DK127786
- National Institute of Diabetes and Digestive and Kidney Diseases
- R01 DK060581
- National Institute of Diabetes and Digestive and Kidney Diseases
- R01 DK133881
- National Institute of Diabetes and Digestive and Kidney Diseases
- R01 DK121929
- National Institute of Diabetes and Digestive and Kidney Diseases
- R01 DK126444
- UAB
- DRC P&F
- UAB
- Comprehensive Diabetes Center