Short-term, Long-term, and Genetic Determinants of Human Plasma Proteome Variability
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Plasma proteomics is increasingly used for biomarker discovery and predictive modeling, yet diurnal protein trajectories remain insufficiently characterized. In our review of recent proteomic biomarker studies, 43% of the identified biomarkers had previously been reported to display 24-h rhythmicity. We demonstrate that ignoring these short-term dynamic effects compromises the robustness of reported models predicting health outcomes. We integrated a population-scale multi-ethnic longitudinal cohort with repeated measures over 10 years, with two cohorts of healthy adults undergoing frequent plasma sampling across days under controlled circadian, sleep and food-intake conditions. This design enabled estimation of short-term intraindividual variability (ST), long-term intraindividual variability (LT), population-level variability (POP) and genetic effects (GEN) across 7,289 protein targets. ST, LT, POP, and GEN define diverse protein trajectories, including rapid dynamics, long-term change, and individual-specific signatures. Using and generalizing this framework will facilitate covariate selection, study design, biomarker prioritization, and variability-aware modeling by users of proteomic data. Graphical abstract
Authors: David Benacom, Adrien Specht, Jayna C Nicholas, Robin Guillard, Madeline Gillman, Ruth Dubin, Peter Ganz, Jerome I Rotter, Kent D Taylor, Stephen S Rich, Peter Y Liu, Alexis C Wood, Michael Y Mi, Rajat Deo, Kirsi-Marja Zitting, Laura M Raffield, Charles A Czeisler, Jeanne F Duffy, Emmanuel Mignot
Institutions: Stanford University, University of North Carolina at Chapel Hill, The University of Texas Southwestern Medical Center, University of California, San Francisco, University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, University of Virginia, Baylor College of Medicine, Children's Nutrition Research Center at Baylor College of Medicine, Beth Israel Deaconess Medical Center, University of Pennsylvania, Brigham and Women's Hospital, Harvard University
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7202023459