SomaScan® Platform confirmation and performance validation
Background
The SomaScan® Platform for proteomic profiling uses 7,288 (7K) SOMAmer® reagents, single-stranded DNA aptamers, to 6,596 unique human protein targets. The modified aptamer binding reagents1, SomaScan Assay2, its performance characteristic for 5K3 and 7K4 content sets, and specificity5,6,7 to human targets have been previously described. We combine profiles of validation and performance metrics with orthogonal confirmation of specificity from published literature to provide a comprehensive view of the specificity and utility of the SomaScan Platform.
Methods
Validation of SOMAmer reagents results in a set of metrics that profile performance of the reagents to the protein standards used
for discovery. These include linear ranges and affinity measures: dose response 50 (apparent K D ), and solution K D . Validation of the SomaScan Platform includes replicates of individual and pooled samples over 15 assay runs in both plasma and serum.
Population ranges and performance are generated from matched plasma and serum drawn from more than 1,000 U.S. normal volunteers. Reproducibility and signaling metrics are summarized and reported. Production use of the SomaScan Platform includes replicates to monitor the accuracy and precision of the assay over time. Results from more than 3,000 replicates are aggregated and reported.
Secondary confirmation of specificity is explored using published outcomes from alternative proteomic or genomic profiling methods. Results are extracted from the literature and assembled by reagent identifier. Alternative experiments that confirm protein targets are described and reported separately.
Conclusion
The SomaScan® Platform for proteomic profiling relies on a deep validation workflow for reagents and for the platform. Transparency in the methods and results is critical to help users interpret platform results.
Authors
Ted Johnson
Darryl Perry
SomaLogic Operating Co., Inc., Boulder, CO USA
References
- Rohloff JC, Gelinas AD, Jarvis TC, et al. Nucleic Acid Ligands With Protein-like Side Chains: Modified Aptamers and Their Use as Diagnostic and Therapeutic Agents. Molecular Therapy Nucleic Acids 2014; 3: e201.
- Gold L, Ayers D, Bertino J, et al. Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoSOne 2010; 5(12): e15004.
- Kim CH, Tworoger SS, Stampfer MJ, et al. Stability and reproducibility of proteomic profiles measured with an aptamer based platform. Sci Rep 2018; 8(1): 8382.
- Candia J, Daya GN, Tanaka T, et al. Assessment of variability in the plasma 7K SomaScan proteomics assay. Sci Rep 12, 17147 (2022).
- Sun BB, Maranville JC, Peters JE, et al. Genomic atlas of the human plasma proteome. Nature 2018; 558(7708): 73-9.
- Emilsson V, Ilkov M, Lamb JR, et al. Co-regulatory networks of human serum proteins link genetics to disease. Science 2018; 361(6404): 769-73.
- Pietzner M, et al. Mapping the proteo-genomic convergence of human diseases. Science 2021; Vol 374, Issue 6569
- Candia J, et al. Assessment of variability in the plasma 7K SomaScan proteomics assay. Sci Rep 2022, Oct 13;12(1):17147. doi: 10.1038/s41598-022-22116-0. PMID: 36229504; PMCID: PMC9561184.
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