A Method for Comparing Proteins Measured in Serum and Plasma by Olink Proximity Extension Assay

Accurate measurement of secreted proteins in serum and plasma is essential for understanding mechanisms and developing reliable biomarkers. Recent technological advancements, such as proximity extension assay (PEA), have enabled high-throughput multiplex protein analyses from small sample volumes in either serum or plasma. Despite the increasing use of PEA-based proteomics and the generation of extensive datasets, integrated data from these two mediums remains challenging due to inherent differences in sample processing. To address this issue, we developed and validated protein-specific transformation factors using linear modeling to normalize protein measurements between serum and plasma proteins quantified using Olink. Our analysis surveyed 1463 proteins across matched serum and plasma samples, identifying 686 transformation factors. The transformation factors were further validated using independent datasets generated from patients with different disease phenotypes and ages, and 551 of the models and transformation factors were reproducible. These transformation factors provide a valuable resource for normalizing PEA-based proteomic data across serum and plasma, ultimately enhancing the capacity for collaborative analyses and facilitating comprehensive insights across diverse disease phenotypes.