Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteome
Abstract Extracellular vesicles (EVs) in plasma are composed of exosomes, microvesicles, and apoptotic bodies. We report a plasma EV enrichment strategy using magnetic beads called Mag-Net. Proteomic interrogation of this plasma EV fraction enables the detection of proteins that are beyond the dynam...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60595-7 |
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| author | Christine C. Wu Kristine A. Tsantilas Jea Park Deanna Plubell Justin A. Sanders Previn Naicker Ireshyn Govender Sindisiwe Buthelezi Stoyan Stoychev Justin Jordaan Gennifer Merrihew Eric Huang Edward D. Parker Michael Riffle Andrew N. Hoofnagle William S. Noble Kathleen L. Poston Thomas J. Montine Michael J. MacCoss |
| author_facet | Christine C. Wu Kristine A. Tsantilas Jea Park Deanna Plubell Justin A. Sanders Previn Naicker Ireshyn Govender Sindisiwe Buthelezi Stoyan Stoychev Justin Jordaan Gennifer Merrihew Eric Huang Edward D. Parker Michael Riffle Andrew N. Hoofnagle William S. Noble Kathleen L. Poston Thomas J. Montine Michael J. MacCoss |
| author_sort | Christine C. Wu |
| collection | DOAJ |
| description | Abstract Extracellular vesicles (EVs) in plasma are composed of exosomes, microvesicles, and apoptotic bodies. We report a plasma EV enrichment strategy using magnetic beads called Mag-Net. Proteomic interrogation of this plasma EV fraction enables the detection of proteins that are beyond the dynamic range of liquid chromatography-mass spectrometry of unfractionated plasma. Mag-Net is robust, reproducible, inexpensive, and requires <100 μL plasma input. Coupled to data-independent mass spectrometry, we demonstrate the measurement of >37,000 peptides from >4,000 proteins. Using Mag-Net on a pilot cohort of patients with neurodegenerative disease and healthy controls, we find 204 proteins that differentiate (q-value < 0.05) patients with Alzheimer’s disease dementia (ADD) from those without ADD. There are also 310 proteins that differ between individuals with Parkinson’s disease and without. Using machine learning we distinguish between individuals with ADD and not ADD with an area under the receiver operating characteristic curve (AUROC) = 0.98 ± 0.06. |
| format | Article |
| id | doaj-art-ff8d68dac6ef4e49a5104f3ced67943e |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ff8d68dac6ef4e49a5104f3ced67943e2025-08-20T03:03:41ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-60595-7Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteomeChristine C. Wu0Kristine A. Tsantilas1Jea Park2Deanna Plubell3Justin A. Sanders4Previn Naicker5Ireshyn Govender6Sindisiwe Buthelezi7Stoyan Stoychev8Justin Jordaan9Gennifer Merrihew10Eric Huang11Edward D. Parker12Michael Riffle13Andrew N. Hoofnagle14William S. Noble15Kathleen L. Poston16Thomas J. Montine17Michael J. MacCoss18Department of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonDepartment of Computer Science, University of WashingtonCSIRReSyn BiosciencesCSIRReSyn BiosciencesReSyn BiosciencesDepartment of Computer Science, University of WashingtonDepartment of Computer Science, University of WashingtonVision Core Lab, Department of Ophthalmology, University of WashingtonDepartment of Biochemistry, University of WashingtonDepartment of Lab Medicine and Pathology, University of WashingtonDepartment of Genome Sciences, University of WashingtonDepartment of Neurology & Neurological Sciences, Stanford UniversityDepartment of Pathology, Stanford UniversityDepartment of Genome Sciences, University of WashingtonAbstract Extracellular vesicles (EVs) in plasma are composed of exosomes, microvesicles, and apoptotic bodies. We report a plasma EV enrichment strategy using magnetic beads called Mag-Net. Proteomic interrogation of this plasma EV fraction enables the detection of proteins that are beyond the dynamic range of liquid chromatography-mass spectrometry of unfractionated plasma. Mag-Net is robust, reproducible, inexpensive, and requires <100 μL plasma input. Coupled to data-independent mass spectrometry, we demonstrate the measurement of >37,000 peptides from >4,000 proteins. Using Mag-Net on a pilot cohort of patients with neurodegenerative disease and healthy controls, we find 204 proteins that differentiate (q-value < 0.05) patients with Alzheimer’s disease dementia (ADD) from those without ADD. There are also 310 proteins that differ between individuals with Parkinson’s disease and without. Using machine learning we distinguish between individuals with ADD and not ADD with an area under the receiver operating characteristic curve (AUROC) = 0.98 ± 0.06.https://doi.org/10.1038/s41467-025-60595-7 |
| spellingShingle | Christine C. Wu Kristine A. Tsantilas Jea Park Deanna Plubell Justin A. Sanders Previn Naicker Ireshyn Govender Sindisiwe Buthelezi Stoyan Stoychev Justin Jordaan Gennifer Merrihew Eric Huang Edward D. Parker Michael Riffle Andrew N. Hoofnagle William S. Noble Kathleen L. Poston Thomas J. Montine Michael J. MacCoss Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteome Nature Communications |
| title | Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteome |
| title_full | Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteome |
| title_fullStr | Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteome |
| title_full_unstemmed | Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteome |
| title_short | Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteome |
| title_sort | enrichment of extracellular vesicles using mag net for the analysis of the plasma proteome |
| url | https://doi.org/10.1038/s41467-025-60595-7 |
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