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Main Authors: Shen, Molly L., Wallucks, Andreas, Martel, Rosalie, Jin, Zijie, Alexandre, Lucile, DeCorwin-Martin, Philippe, de Araujo, Lorenna Oliveira Fernandes, Ng, Andy, Siegel, Peter M., Juncker, David
Format: Preprint
Published: 2023
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Online Access:https://arxiv.org/abs/2301.04051
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author Shen, Molly L.
Wallucks, Andreas
Martel, Rosalie
Jin, Zijie
Alexandre, Lucile
DeCorwin-Martin, Philippe
de Araujo, Lorenna Oliveira Fernandes
Ng, Andy
Siegel, Peter M.
Juncker, David
author_facet Shen, Molly L.
Wallucks, Andreas
Martel, Rosalie
Jin, Zijie
Alexandre, Lucile
DeCorwin-Martin, Philippe
de Araujo, Lorenna Oliveira Fernandes
Ng, Andy
Siegel, Peter M.
Juncker, David
contents Extracellular vesicles (EVs) are cell-derived secretions that mediate tissue homeostasis and intercellular communication through their diverse cargos, such as proteins. Distinct EV biogenesis pathways suggest specific association and co-enrichment of proteins sharing a biogenesis pathway, and non-association and co-depletion of proteins segregated into distinct pathways. Yet these associations elude conventional protein expression or co-expression measurements. Here, we propose and define pairwise protein co-enrichment (CoEn) to quantify whether a given protein is co-enriched or co-depleted with another protein relative to its overall expression. We measure CoEn, and differential CoEn (dCoEn) between a stimulus and a reference condition, of up to 240 protein pairs in EVs using antibody microarrays. We validate CoEn by modulating well-known EV biogenesis pathways, and find that dCoEn quantifies expected changes between perturbed and reference conditions while uncovering new ones; CoEn and dCoEn in three model cell lines and parental and organotropic breast cancer progeny cell lines reveals both preserved and variable CoEn that may warrant further studies. Collectively, our result suggest that CoEn reflects and illuminates cell physiology and EV biogenies, is readily measurable, and could further serve as quality control in EV biomanufacturing as well as underpin new EV biomarkers.
format Preprint
id arxiv_https___arxiv_org_abs_2301_04051
institution arXiv
publishDate 2023
record_format arxiv
spellingShingle Co-Enrichment of Proteins in Extracellular Vesicles
Shen, Molly L.
Wallucks, Andreas
Martel, Rosalie
Jin, Zijie
Alexandre, Lucile
DeCorwin-Martin, Philippe
de Araujo, Lorenna Oliveira Fernandes
Ng, Andy
Siegel, Peter M.
Juncker, David
Quantitative Methods
Extracellular vesicles (EVs) are cell-derived secretions that mediate tissue homeostasis and intercellular communication through their diverse cargos, such as proteins. Distinct EV biogenesis pathways suggest specific association and co-enrichment of proteins sharing a biogenesis pathway, and non-association and co-depletion of proteins segregated into distinct pathways. Yet these associations elude conventional protein expression or co-expression measurements. Here, we propose and define pairwise protein co-enrichment (CoEn) to quantify whether a given protein is co-enriched or co-depleted with another protein relative to its overall expression. We measure CoEn, and differential CoEn (dCoEn) between a stimulus and a reference condition, of up to 240 protein pairs in EVs using antibody microarrays. We validate CoEn by modulating well-known EV biogenesis pathways, and find that dCoEn quantifies expected changes between perturbed and reference conditions while uncovering new ones; CoEn and dCoEn in three model cell lines and parental and organotropic breast cancer progeny cell lines reveals both preserved and variable CoEn that may warrant further studies. Collectively, our result suggest that CoEn reflects and illuminates cell physiology and EV biogenies, is readily measurable, and could further serve as quality control in EV biomanufacturing as well as underpin new EV biomarkers.
title Co-Enrichment of Proteins in Extracellular Vesicles
topic Quantitative Methods
url https://arxiv.org/abs/2301.04051