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Facets of individual-specific health signatures determined from longitudinal plasma proteome profiling

By Tea Dodig-Crnković, Mun-Gwan Hong, Cecilia Engel Thomas, Ragna S. Häussler, Annika Bendes, Matilda Dale, Fredrik Edfors, Björn Forsström, Patrik K. E. Magnusson, Ina Schuppe-Koistinen, Jacob Odeberg, Linn Fagerberg, Anders Gummesson, Göran Bergström, Mathias Uhlèn, Jochen M. Schwenk

Posted 15 Mar 2020
bioRxiv DOI: 10.1101/2020.03.13.988683

Background: Precision medicine approaches aim to tackle diseases on an individual level through molecular profiling. Despite the growing knowledge about diseases and the reported diversity of molecular phenotypes, the descriptions of human health on an individual level have been far less elaborate. Methods: To provide insights into the longitudinal protein signatures of well-being, we profiled blood plasma collected over one year from 101 clinically healthy individuals using multiplexed antibody assays. After applying an antibody validation scheme, we utilized > 700 protein profiles for in-depth analyses of the individuals' short-term health trajectories. Findings: We found signatures of circulating proteomes to be highly individual-specific. Considering technical and longitudinal variability, we observed both stable and fluctuating proteins in the circulation, as well as networks of proteins that covaried over time. For each participant, there were unique protein profiles and some of these could be explained by associations to genetic variants. Interpretation: This study demonstrates that there was noticeable diversity among clinically healthy subjects, and facets of individual-specific signatures emerged by monitoring the variability of the circulating proteomes over time. Longitudinal profiling of circulating proteomes has the potential to enable a more personal hence precise assessment of health states, and thereby provide a valuable component of precision medicine approaches. Funding: This work was supported by the Erling Persson Foundation for the KTH Centre for Precision Medicine and the Swedish Heart and Lung Foundation for the SCAPIS project. We also acknowledge the Knut and Alice Wallenberg Foundation for funding the Human Protein Atlas project, Science for Life Laboratory for Plasma Profiling Facility, and the Swedish Research Council (Grant no 2017-00641).

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