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Cited by 25Advanced Proteomics Techniques and ApplicationsAdvanced Biosensing Techniques and ApplicationsMass Spectrometry Techniques and Applications

Comparative evaluation of Olink Explore 3072 and mass spectrometry with peptide fractionation for plasma proteomics

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Sissala, Noora, Babačić, Haris, Leo, Isabelle R., Cao, Xiaofang, Forshed, Jenny, Eriksson, Lars E., Lehtiö, Janne, Fredolini, Claudia +2 more·2025·Communications Chemistry
DOI 10.1038/s42004-025-01753-2PMC PMC12586489

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Abstract

Plasma proteomics technologies are advancing rapidly, offering new opportunities for biomarker discovery and precision medicine. Direct comparisons of available technologies are needed to understand how platform selection affects downstream findings. We compared the performance of a peptide fractionation-based mass spectrometry method (HiRIEF LC-MS/MS) and the Olink Explore 3072 proximity extension assays on 88 plasma samples, analyzing 1129 proteins with both methods. The platforms exhibited complementary proteome coverage, high precision, and concordance in estimating sex differences in protein levels. Quantitative agreement between platforms was moderate (median correlation 0.59, interquartile range 0.33-0.75), mainly influenced by technical factors. Finally, we present a publicly available tool for peptide-level analysis of platform agreement and demonstrate its utility in clarifying cross-platform discrepancies in protein and proteoform measurements. Our findings provide insights for platform selection and study design, and highlight the value of combining mass spectrometry and affinity-based approaches for more comprehensive and reliable plasma proteome profiling.

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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 [41]

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Cited by

Sorted by citations

Authors
Sissala, N., Babačić, H., Leo, I. R., Cao, X., Forshed, J., Eriksson, L. E., Lehtiö, J., Fredolini, C., Åberg, M., & Pernemalm, M.
Affiliations
  • Science for Life Laboratory (SE)
  • Karolinska Institutet (SE)
  • Uppsala University (SE)
Corresponding author
  • Sissala, Noora
  • Pernemalm, Maria
ORCID
Venue
Communications Chemistry
Publisher
Springer Science and Business Media LLC
Published
2025-11-04
Volume
8
Issue
1
Pages
327-327
ISSN
2399-3669 (ISSN-L)
DOI
10.1038/s42004-025-01753-2
PMC
PMC12586489
OpenAlex
W4415881868
Cited by
25
References
5
Citations by year
2026: 25
FWCI
6.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Chemistry (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • City Research Online (City University London) (acceptedVersion)
  • Diva portal (Dalarna University Library) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Vetenskapsrådet (2022-01176)
  • Cancerföreningen i Stockholm (211073)
  • Science for Life Laboratory
  • National Institute of Allergy and Infectious Diseases (T32AI155387)
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, proximity extension assay, peptide fractionation, platform comparison, proteoforms, biomarker discovery, platform selection

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