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Cited by 111Advanced Proteomics Techniques and ApplicationsAdvanced Biosensing Techniques and ApplicationsMass Spectrometry Techniques and Applications

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Current landscape of plasma proteomics from technical innovations to biological insights and biomarker discovery

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Kirsher, Douglas Y., Chand, Shreya, Phong, Aron, Nguyen, Bich, Szoke, Balazs G., Ahadi, Sara·2025·Communications Chemistry
DOI 10.1038/s42004-025-01665-1PMC PMC12462477
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Abstract

Abstract Plasma is a rich source of biomolecules, including proteins, that reflect both health and disease. Due to their key roles in biological processes, proteins hold significant potential as biomarkers, fueling the rise of plasma proteome profiling in recent years. Despite widespread adoption, few studies have directly compared different plasma proteomics platforms, particularly those using mass spectrometry. Our study provides a comprehensive comparison of seven platforms across three leading technologies - SomaLogic, Olink, and Mass Spectrometry (MS) - including affinity-based approaches and various MS techniques, covering over 13,000 proteins. By applying these methods to the same cohort, we assess their performance, revealing key differences and complementary strengths. Our findings offer valuable insights for researchers, highlighting trade-offs in coverage and their implications for biomarker discovery and clinical applications. This study serves as an essential resource, offering both technical evaluation and biological insights to support the development of novel diagnostics and therapeutics through plasma proteomics.

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  • Platform comparisons incorporating MS protein measures are already proving informative to further depict genetically encoded isoform differences and impacts of splicing on detected protein structures.

    “Platform comparisons incorporating MS protein measures are already proving informative to further depict genetically encoded isoform differences and impacts of splicing on detected protein structures24,40,41, and will be especially important to expand across ancestrally diverse sets of participants.”

    From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [40]

    In Results and discussion, under “Correlations between shared proteins among platforms” (Fig. 4; page not provided), the paper uses MS peptides to compare genetically encoded ApoE isoforms across platforms and assess isoform specificity. It does not report effects of splicing on detected protein structures; a search for alternative splicing found no passage addressing that part of the claim. (LLM, conf=0.86)

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  • The SomaScan assay uses DNA-based slow off-rate modified aptamers (SOMAmer reagents) to quantify the relative abundance of approximately 7000 proteins with high specificity and limits of detection largely comparable to antibody-based assays.

    “The assay uses DNA-based slow off-rate modified aptamers (SOMAmerTM reagents) to quantify the relative abundance of approximately 7000 proteins with high specificity and limits of detection largely comparable to antibody-based assays.”

    From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [40]

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Metadata

Authors
Kirsher, D. Y., Chand, S., Phong, A., Nguyen, B., Szoke, B. G., & Ahadi, S.
Affiliations
Alkahest, Inc. (United States) (US)
Corresponding author
Ahadi, Sara
ORCID
Venue
Communications Chemistry
Publisher
Springer Science and Business Media LLC
Published
2025-09-25
Volume
8
Issue
1
Pages
279-279
ISSN
2399-3669 (ISSN-L)
DOI
10.1038/s42004-025-01665-1
PMC
PMC12462477
OpenAlex
W4414514925
Cited by
111
References
8
Citations by year
2026: 96 · 2025: 14
FWCI
26.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Chemistry (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Grifols
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
Keywords
plasma proteomics, biomarker discovery

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