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Cited by 206Advanced Biosensing Techniques and ApplicationsAdvanced Proteomics Techniques and ApplicationsBiomarkers in Disease Mechanisms

Proteomic profiling platforms head to head: Leveraging genetics and clinical traits to compare aptamer- and antibody-based methods

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Katz, Daniel H., Robbins, Jeremy M., Deng, Shuliang, Tahir, Usman A., Bick, Alexander G., Pampana, Akhil, Yu, Zhi, Ngo, Debby +11 more·2022·Science Advances
DOI 10.1126/sciadv.abm5164PMC PMC9390994
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Abstract

High-throughput proteomic profiling using antibody or aptamer-based affinity reagents is used increasingly in human studies. However, direct analyses to address the relative strengths and weaknesses of these platforms are lacking. We assessed findings from the SomaScan1.3K ( N = 1301 reagents), the SomaScan5K platform ( N = 4979 reagents), and the Olink Explore ( N = 1472 reagents) profiling techniques in 568 adults from the Jackson Heart Study and 219 participants in the HERITAGE Family Study across four performance domains: precision, accuracy, analytic breadth, and phenotypic associations leveraging detailed clinical phenotyping and genetic data. Across these studies, we show evidence supporting more reliable protein target specificity and a higher number of phenotypic associations for the Olink platform, while the Soma platforms benefit from greater measurement precision and analytic breadth across the proteome.

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  • 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 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 [12]

    In Results, ‘Accuracy: Platform correlation and cis pQTLs’ (page unavailable), the paper reports that highly correlated Olink–SomaScan reagent pairs were likely to show cis-pQTLs on both platforms. It also reports that lower-correlation pairs were more likely to show a cis-pQTL on Olink only. The evidence therefore supports an association with detection on both platforms, but not the unqualified claim that detecting a cis-pQTL for a protein measure is a strong predictor of its inter-platform correlation coefficient. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Proximity extension assays have been shown to be sensitive and specific.

    “We mainly used proximity extension assays (PEA), which have been shown to be sensitive and specific (Assarsson et al, 2014; Katz et al, 2022)”

    From The genetic regulation of protein expression in cerebrospinal fluid (2023) · cites this paper as Katz et al, 2022

    The Discussion (page unavailable) reports evidence supporting the specificity of Olink’s proximity-extension-based measurements, including cis-pQTL associations and agreement with ELISA for four proteins. It does not establish generally high sensitivity: the authors say they could not independently determine detection limits, although the reagents in their ELISA validation quantified at least as low as the levels measured by ELISA. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Existing 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 [12]

  • 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 [12]

  • The 644 proteins with a cis-pQTL detected on both platforms had higher inter-platform correlation (mean Pearson r = 0.58, SD = 0.20) than proteins with no significant cis-pQTL (mean r = 0.21, SD = 0.30).

    “Similar to prior studies12,17, the 644 proteins with a cis-pQTL detected on both platforms had higher inter-platform correlation (mean Pearson’s r = 0.58, SD = 0.20) than proteins with no significant cis-pQTL (mean Pearson’s r = 0.21, SD = 0.30)(Fig. 3C and Supplementary Data 7).”

    From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [12]

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Authors
Katz, D. H., Robbins, J. M., Deng, S., Tahir, U. A., Bick, A. G., Pampana, A., Yu, Z., Ngo, D., Benson, M. D., Chen, Z.-Z., Cruz, D. E., Shen, D., Gao, Y., Bouchard, C., Sarzynski, M. A., Correa, A., Natarajan, P., Wilson, J. G., & Gerszten, R. E.
Affiliations
  • Beth Israel Deaconess Medical Center (US)
  • Broad Institute (US)
  • University of Mississippi Medical Center (US)
  • Pennington Biomedical Research Center (US)
  • University of South Carolina (US)
Corresponding author
Gerszten, Robert E.
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-08-19
Volume
8
Issue
33
Pages
eabm5164-eabm5164
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.abm5164
PMC
PMC9390994
OpenAlex
W4293102181
Cited by
206
References
55
Citations by year
2026: 45 · 2025: 63 · 2024: 50 · 2023: 44 · 2022: 4
FWCI
13.31
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science Advances (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Scholar Commons (University of South Carolina) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (KL2TR002542, 1r01hl120393-01a1, DP5OD029586, 5t32hl007374-41)
  • National Institute on Aging (RF1AG063507)
  • National Heart, Lung, and Blood Institute (R01HL047327, HHSN268201100037C, R01HL127564, HHSN268201800012C, R01-HL120393, HHSN268201800010 I, T32‐HL007374, HHSN268201800014 I, HHSN268201800001C, HHSN268201800012 I, R01HL047317, R01HL132320, U01HL120393, HHSN268201800014C, K08HL145095, HHSN268201800015I, K23HL150327, HHSN268201800011C, HHSN268201800011I, R01HL047323, R01HL146462, R01HL117626, F32HL150992, R01HL045670, R01HL142711, R01HL133870)
  • National Institute of Nursing Research (R01NR019628)
  • National Institute of General Medical Sciences (P30GM118430)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U24DK112340, R01DK081572)
  • National Center for Advancing Translational Sciences
  • National Institute on Minority Health and Health Disparities (HHSN268201800013I)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Keywords
proteomic profiling, SomaScan, platform comparison, measurement precision, phenotypic association, genetic data, Jackson Heart Study, HERITAGE Family Study, human proteome
MeSH terms
Adult, Antibodies, Humans, Longitudinal Studies, Phenotype, Proteome, Proteomics, Aptamers, Peptide

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