Comparison of Proteomic Assessment Methods in Multiple Cohort Studies
Open accessAbstract
Novel proteomics platforms, such as the aptamer‐based SOMAscan platform, can quantify large numbers of proteins efficiently and cost‐effectively and are rapidly growing in popularity. However, comparisons to conventional immunoassays remain underexplored, leaving investigators unsure when cross‐assay comparisons are appropriate. The correlation of results from immunoassays with relative protein quantification is explored by SOMAscan. For 63 proteins assessed in two chronic obstructive pulmonary disease (COPD) cohorts, subpopulations and intermediate outcome measures in COPD Study (SPIROMICS), and COPDGene, using myriad rules based medicine multiplex immunoassays and SOMAscan, Spearman correlation coefficients range from −0.13 to 0.97, with a median correlation coefficient of ≈0.5 and consistent results across cohorts. A similar range is observed for immunoassays in the population‐based Multi‐Ethnic Study of Atherosclerosis and for other assays in COPDGene and SPIROMICS. Comparisons of relative quantification from the antibody‐based Olink platform and SOMAscan in a small cohort of myocardial infarction patients also show a wide correlation range. Finally, cis pQTL data, mass spectrometry aptamer confirmation, and other publicly available data are integrated to assess relationships with observed correlations. Correlation between proteomics assays shows a wide range and should be carefully considered when comparing and meta‐analyzing proteomics data across assays and studies.
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The detection of a cis-pQTL for a given protein measure is often used as a metric to confirm on-target affinity-probe binding.
“The detection of a cis-pQTL for a given protein measure is often used as a metric to confirm on-target affinity-probe binding12,15,16; existing studies comparing SomaScan and Olink measures have established that the detection of a cis-pQTL is a strong predictor of inter-platform correlation coefficients for a given protein12,15,16.”
From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [15]
The Discussion says cis-pQTL presence can provide clues to assay specificity and suggests that a probe has at least some binding to its target protein. It does not treat a cis-pQTL as confirmation of on-target binding: it cautions that binding differences can produce spurious pQTLs and that a cis-pQTL does not exclude off-target binding. (LLM, conf=0.86)
Experimental — accuracy not yet measuredExisting comparisons of SomaScan and Olink platforms have shown that some protein measures are not concordant, with median inter-platform correlation = 0.38-0.50, which challenges the accuracy of protein associations observed.
“However, existing comparisons of SomaScan and Olink platforms have shown that some protein measures are not concordant (median inter-platform correlation = 0.38–0.50)11–16, which challenges the accuracy of protein associations observed, especially as there is no “gold-standard” reference measure for most proteins.”
From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [15]
The Results (Summary; page unavailable) report poor concordance for some SomaScan–Olink protein measures, and the Discussion recommends validating key findings with other methods. However, the Results give a median SomaScan–Olink correlation of 0.36, not 0.38–0.50; the reported 0.38 median is for SomaScan versus MSD. (LLM, conf=0.90)
Experimental — accuracy not yet measuredExisting studies comparing SomaScan and Olink measures have established that the detection of a cis-pQTL is a strong predictor of inter-platform correlation coefficients for a given protein.
“The detection of a cis-pQTL for a given protein measure is often used as a metric to confirm on-target affinity-probe binding12,15,16; existing studies comparing SomaScan and Olink measures have established that the detection of a cis-pQTL is a strong predictor of inter-platform correlation coefficients for a given protein12,15,16.”
From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [15]
The Results section reports that proteins with a SOMAscan cis-pQTL were enriched among the more highly correlated SOMAscan–Olink measures. But the Discussion says the Olink–SOMAscan dataset was too small for cis-pQTL analysis, and cautions that a cis-pQTL does not guarantee high inter-assay correlation. The paper therefore supports an association, not the claim that cis-pQTL detection was established as a strong predictor of correlation coefficients. (LLM, conf=0.86)
Experimental — accuracy not yet measuredcis-pQTL presence/absence is thought to provide one predictor of on-target protein measures.
“Here, and across prior studies, cis-pQTL presence/absence is thought to provide one predictor of on-target protein measures12,15,16.”
From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [15]
The modest overlap between our findings and aptamer-based studies is unsurprising because correlations between proteins measured by both platforms are highly variable and shared genetic signals can be masked by extreme, assay-specific binding affinities.
“This modest overlap is unsurprising, given that correlations between proteins measured by both platforms are highly variable 52,53 , and shared genetic signals can be masked by extreme, assay-specific binding affinities 51 .”
From Plasma proteomic associations with genetics and health in the UK Biobank (2023) · cites this paper as [53]
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Drouard, G., Suhonen, S., Heikkinen, A., Wang, Z., Kaprio, J. A., & Ollikainen, M. (2025) · Aging Cell · doi:10.1111/acel.70088 · Cited by 6 · see citing works
- Authors
- Raffield, L. M., Dang, H., Pratte, K. A., Jacobson, S., Gillenwater, L. A., Ampleford, E., Barjaktarevic, I., Basta, P., Clish, C. B., Comellas, A. P., Cornell, E., Curtis, J. L., Doerschuk, C., Durda, P., Emson, C., Freeman, C. M., Guo, X., Hastie, A. T., Hawkins, G. A., Herrera, J., Johnson, W. C., Labaki, W. W., Liu, Y., Masters, B., Miller, M., Ortega, V. E., Papanicolaou, G., Peters, S., Taylor, K. D., Rich, S. S., Rotter, J. I., Auer, P., Reiner, A. P., Tracy, R. P., Ngo, D., Gerszten, R. E., O'Neal, W. K., Bowler, R. P., & NHLBI Trans‐Omics for Precision Medicine (TOPMed) Consortium
- Affiliations
- University of North Carolina at Chapel Hill (US)
- National Jewish Health (US)
- Wake Forest University Health Sciences (US)
- UCLA Division of Pulmonary and Critical Care David Geffen School of Medicine University of California Los Angeles Los Angeles CA 90095
- Broad Institute (US)
- University of Iowa (US)
- University of Vermont (US)
- University of Michigan (US)
- AstraZeneca (United States) (US)
- The Lundquist Institute (US)
- ProterixBio (United States) (US)
- University of Washington (US)
- National Heart, Lung, and Blood Institute (US)
- University of Virginia (US)
- University of Wisconsin–Milwaukee (US)
- Beth Israel Deaconess Medical Center (US)
- Marsico Lung Institute University of North Carolina at Chapel Hill Chapel Hill NC 27599
- Corresponding author
- Raffield, Laura M.
- ORCID
- Raffield, Laura M.
- Dang, Hong
- Pratte, Katherine A.
- Jacobson, Sean
- Gillenwater, Lucas A.
- Basta, Patricia
- Clish, Clary B.
- Comellas, Alejandro P.
- Curtis, Jeffrey L.
- Doerschuk, Claire
- Durda, Peter
- Emson, Claire
- Freeman, Christine M.
- Guo, Xiuqing
- Hastie, Annette T.
- Johnson, W. Craig
- Labaki, Wassim W.
- Miller, Michael
- Ortega, Victor E.
- Papanicolaou, George
- Peters, Stephen
- Taylor, Kent D.
- Rich, Stephen S.
- Rotter, Jerome I.
- Auer, Paul
- Reiner, Alex P.
- Tracy, Russell P.
- Ngo, Debby
- Gerszten, Robert E.
- Bowler, Russell P.
- Venue
- PROTEOMICS
- Publisher
- Wiley
- Published
- 2020-06
- Volume
- 20
- Issue
- 12
- Pages
- e1900278-e1900278
- ISSN
- 1615-9853 (ISSN-L)
- 1615-9861
- PMC
- PMC7425176
- OpenAlex
- W3022509738
- Cited by
- 184
- References
- 36
- Citations by year
- 2026: 33 · 2025: 31 · 2024: 33 · 2023: 37 · 2022: 29 · 2021: 19 · 2020: 1 · 2012: 1
- FWCI
- 6.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- PROTEOMICS (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (Merit Review I01 CX000911)
- National Heart, Lung, and Blood Institute (R01 HL132947, T32 HL007749, T32 HL129982)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- SomaScan, aptamer-based proteomics, relative protein quantification, proteomics data integration, chronic obstructive pulmonary disease, myocardial infarction, cis-pQTL
- MeSH terms
- Smokers, Adult, Aged, Aged, 80 and over, Female, Humans, Immunoassay, Male, Middle Aged, Myocardial Infarction, Cohort Studies, Proteome, Pulmonary Disease, Chronic Obstructive, Proteomics
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