Evidence map›Paper›PMID 40955644›Full record

ReviewProteomics2026

Challenges and Opportunities in State-of-the-Art Proteomics Analysis for Biomarker Development From Plasma Extracellular Vesicles.

Panshak P Dakup, Ivo Diaz Ludovico, Youngki You, Chaitra Rao, Javier Flores, Lisa M Bramer, Marian Rewers, Bobbie-Jo M Webb-Robertson, Thomas O Metz, Raghavendra G Mirmira and 2 more

Abstract readReview
In one paragraph

Review in Proteomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Panshak P DakupBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0003-3534-7744
Ivo Diaz LudovicoBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-3475-5191
Youngki YouBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-2189-9049
Chaitra RaoDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.ORCID 0000-0002-2834-7458
Javier FloresBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-1550-1655
Lisa M BramerBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-8384-1926
Marian RewersBarbara Davis Center For Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID 0000-0003-3829-9207
Bobbie-Jo M Webb-RobertsonBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-4744-2397
Thomas O MetzBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0001-6049-3968
Raghavendra G MirmiraDepartment of Medicine and the Kovler Diabetes Center, The University of Chicago, Chicago, Illinois, USA.ORCID 0000-0002-5013-6075
Emily K SimsDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.ORCID 0000-0002-4393-954X
Ernesto S NakayasuBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-4056-2695

Funding

Renewal of the Human Islet Research Enhancement Center (HIREC) for the Type-1-Diabetes-Focused Human Islet Research Network (HIRN).U24DK104162 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI John S. Kaddis, Joyce Carol Niland · 2019 to 2026
$12.3M
Transcriptional Mechanisms Governing Beta Cell DifferentiationR01DK060581 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Raghavendra G Mirmira · 2002 to 2026
$8.5M
The Integrated Stress Response in Human Islets During Early T1DU01DK127786 · NIDDK · UNIVERSITY OF CHICAGO · PI EVANS-MOLINA, CARMELLA, MIRMIRA, RAGHAVENDRA G · 2020 to 2025
$7.1M
Role of Polyamines and Hypusine in Nutrient-Induced Beta-Cell Growth and ReplicationR01DK124906 · NIDDK · UNIVERSITY OF CHICAGO · PI Raghavendra G Mirmira · 2020 to 2026
$4.0M
Alternative RNA splicing events contribute to the onset of islet dysfunction in T1DU01DK127505 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI NAKAYASU, ERNESTO SATOSHI, SUSSEL, LORI · 2020 to 2023
$2.9M
Implications of Changes in Islet Exosomal Cargo in Type 1 DiabetesR01DK133881 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI EVANS-MOLINA, CARMELLA, MIRMIRA, RAGHAVENDRA G · 2022 to 2025
$2.7M
Beta cell extracellular vesicles in health and diseaseR01DK121929 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI SIMS, EMILY K · 2020 to 2024
$2.0M
Systematic validation of biomarkers predictive of IA and T1D and their relationship with disease developmentR01DK138335 · NIDDK · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI Thomas O Metz, Ernesto Satoshi Nakayasu · 2024 to 2026
$1.9M
Breakthrough T1D fellowship 3-PDF-2024-1496-A-NDiabetes Research ConnectionNIDDK NIH HHS R01 DK060581NIDDK NIH HHS R01 DK121929NIDDK NIH HHS R01 DK124906NIDDK NIH HHS R01 DK133881NIDDK NIH HHS R01 DK138335NIDDK NIH HHS U01 DK127505NIDDK NIH HHS U01 DK127786NIDDK NIH HHS U24 DK104162
6 · The paper itself

Abstract

Extracellular vesicles (EVs) are membrane-bound particles secreted by cells, playing crucial roles in intercellular communication. The composition of EVs can undergo changes in response to stress and disease conditions, making them excellent biomarker candidates. However, extracting protein information from EVs can be challenging due to their low abundance in complex biofluids and copurification with contaminant proteins and particles. Techniques to enrich EVs have their strengths and limitations, without one being able to purify EVs to complete homogeneity. This can lead to compromised recovery rates and increased complexity, making data interpretation difficult. In this viewpoint article, we explore the concept that better characterization of EV composition, followed by quantification of EV proteins in complex samples, might be a more viable route for biomarker development. Mass spectrometers can provide reproducible deep coverage of the EV proteome, despite sample impurities. This paradigm shift presents opportunities to integrate advanced bioinformatics tools to refine the EV proteome landscape, identify novel biomarkers, and streamline validation processes in biomarker development. By focusing on leveraging technology rather than achieving absolute purity, this approach can transform current practices and open opportunities for robust biomarker discovery. Herein, we highlight not only such opportunities but also challenges to implement this concept. SUMMARY: Extracellular vesicles (EVs) have enormous potential as biomarkers of diseases, as they can carry signatures of the cells they are derived from and the pathogenesis process. Biofluids, such as blood plasma, are highly complex and contain many components with physicochemical properties similar to those of EVs, making it challenging to obtain pure EV fractions. Challenges in obtaining pure preparations represent a main hurdle for studying EVs, and their components are potential biomarkers. This article explores the concept of studying EV proteins within complex samples, discussing opportunities and needs to move this field forward.

Indexed as

BiomarkersExtracellular VesiclesProteomeProteomicsHumansMass SpectrometryBiomarkersProteome

Identifiers

PMID40955644
PMCPMC12604859

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.