Assessment of Variability in the SOMAscan Assay

TLDR

SOMAscan is an aptamer‑based proteomics assay that measures 1,305 human proteins in serum, plasma, and other matrices with high sensitivity and specificity. The study conducts a comprehensive meta‑analysis of SOMAscan performance across 1.3k and 1.1k assay versions, develops a statistical framework using calibrator‑derived coefficients of variation, evaluates baseline stability, and delivers an interactive web tool for data sharing and reproducibility. The authors analyze multiple serum and plasma runs, discuss normalization and strategies to minimize intra‑ and inter‑plate nuisance effects, estimate coefficients of variation and signal‑over‑background for each analyte, and incorporate these estimates into a theoretical model to enable rigorous statistical testing and quality control across laboratories.

Abstract

SOMAscan is an aptamer-based proteomics assay capable of measuring 1,305 human protein analytes in serum, plasma, and other biological matrices with high sensitivity and specificity. In this work, we present a comprehensive meta-analysis of performance based on multiple serum and plasma runs using the current 1.3 k assay, as well as the previous 1.1 k version. We discuss normalization procedures and examine different strategies to minimize intra- and interplate nuisance effects. We implement a meta-analysis based on calibrator samples to characterize the coefficient of variation and signal-over-background intensity of each protein analyte. By incorporating coefficient of variation estimates into a theoretical model of statistical variability, we also provide a framework to enable rigorous statistical tests of significance in intervention studies and clinical trials, as well as quality control within and across laboratories. Furthermore, we investigate the stability of healthy subject baselines and determine the set of analytes that exhibit biologically stable baselines after technical variability is factored in. This work is accompanied by an interactive web-based tool, an initiative with the potential to become the cornerstone of a regularly updated, high quality repository with data sharing, reproducibility, and reusability as ultimate goals.