Comparative evaluation of Olink Explore 3072 and mass spectrometry with peptide fractionation for plasma proteomics.
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Sissala N, Babačić H, Leo IR, Cao X, Forshed J, Eriksson LE, Lehtiö J, Fredolini C, Åberg M, Pernemalm M
Commun Chem 8 (1) 327 [2025-11-04; online 2025-11-04]
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.
Affinity Proteomics Stockholm [Collaborative]
NGI Uppsala (SNP&SEQ Technology Platform) [Service]
National Genomics Infrastructure [Service]
PubMed 41188494
DOI 10.1038/s42004-025-01753-2
Crossref 10.1038/s42004-025-01753-2
pii: 10.1038/s42004-025-01753-2
pmc: PMC12586489