A proteomic meta-analysis refinement of plasma extracellular vesicles
Milene C. Vallejo, Soumyadeep Sarkar, Emily C. Elliott, Hayden R. Henry, Samantha Powell, Ivo Diaz Ludovico, Youngki You, Fei Huang, Samuel Payne, Sasanka Ramanadham, Emily K. Sims, Thomas Metz, Raghavendra G. Mirmira, Ernesto Nakayasu
Abstract
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.