The unexplainable plasma protein measurements from Proximity Extension Assays

Plasma proteomics assays aim to capture biologically interpretable circulating protein signals. Here we systematically assess Olink Explore targets with exceptionally low variance explainability by integrating genetic associations, cross-platform concordance and tissue and peptide atlases. We identify a subset of protein targets likely lacking robust plasma signals, highlighting assay- and tissue-specific limitations with implications for panel design, statistical power and interpretation of large-scale proteomics studies.