A standardized framework for circulating blood proteomics

The circulating blood proteome holds immense potential for biomarker discovery and understanding disease mechanisms. Notable advances in mass spectrometry and affinity-based technologies have been made, but data integration across studies and platforms is hindered by the absence of unified analytical standards. This limitation impedes comprehensive exploration of human biology across diverse phenotypes and cohorts as well as the translation of findings into clinical applications. The disparities between datasets, stemming from a combination of factors related to differences in sample collection, pre-analytical handling, measurement methods and instrumentation, further complicate data integration. In this Perspective, we outline key challenges in blood-based proteomics and propose actionable strategies. Central to our recommendations are high-quality, technology-agnostic reference samples, which can bridge disparate datasets and enable robust cross-study comparisons. By fostering interconnected investigations across proteomic technologies, blood sample collections, clinical phenotypes and different populations, these references will accelerate the field and its translation.