BOULDER, Colo., May 14, 2021 — Researchers at the University of Cambridge report the largest, systematic assessment of two different affinity-based proteomic platform technologies to date. By truncating the 5000-plex aptamer-based SomaScan® Assay results down to consider approximately 900 overlapping targets on a polyclonal antibody-based assay and running both assays on the same 485 genotyped samples, the researchers successfully replicated most proteogenomic signals on both platforms. A preprint describing the study is available on bioRxiv.
The researchers use both aptamer-based and antibody-based assays to link genetic variants to changes in blood levels of proteins. These proteogenomic associations, known as protein quantitative trait loci or pQTLs, can provide evidence of causal factors in disease and are used by major pharmaceutical companies to prioritize protein drug targets or repurpose existing drugs. Genetic variants located within or around the gene that encodes the measured protein, called cis-pQTLs, represent the best independent truth standard for testing whether a protein measurement technique is correctly identifying its intended targets.
“The ability of the SomaScan Platform to identify a similar number of cis-pQTLs for the same proteins measured on the same samples confirms that the exquisite specificity of aptamers is a match for antibody pairs,” said Stephen Williams, Chief Medical Officer of SomaLogic and a co-author on the study. “Expanding the data set to include the thousands of protein targets uniquely measured by the SomaScan Platform demonstrates the superior breadth of aptamer-based methods for large-scale proteomics at the population level.”
For 871 proteins that were shared between the two proteomic platforms, the detection of cis-pQTLs was equivalent, and the degree of agreement across platforms was 60 to 70 percent. Some of the differences could be explained by the distinct measurement characteristics of aptamers vs. polyclonal antibody pairs.
Unlike antibodies, aptamers can be highly multiplexed to detect several thousands of protein targets at a time. The cross-platform comparison was therefore limited to the fraction of proteins measured by both techniques in 485 participants of the Fenland Study, a population-based cohort of 12,435 adults aged 29-64 years old from the Cambridgeshire region of the UK. When the study sample was expanded to the whole Fenland cohort, the researchers found pQTLs for approximately 40 percent of the nearly 5,000 proteins measured by the aptamer-based SomaScan Assay.
At the time of the study, the SomaScan Assay measured 5,000 proteins. The current version of the assay measures over 7,000 proteins simultaneously in a single biological sample.
SomaLogic seeks to deliver precise, meaningful, and actionable health-management information that empowers individuals worldwide to continuously optimize their personal health and wellness throughout their lives. This essential information, to be provided through a global network of partners and users, is derived from SomaLogic’s precise, proprietary, and personalized measurement of important changes in an individual’s proteins over time.
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Laura S. Mizoue, Ph.D.