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Gummesson, A.

Publications and source records attributed to Gummesson, A..

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

BackgroundPrecision 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. MethodsTo 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. FindingsWe 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. InterpretationThis 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. FundingThis 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).

biochemistry

Human immune system variation during one year

The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components, and the inference of global regulatory principles. Here we present a longitudinal, systems-level analysis in 99 healthy adults, 50 to 65 years of age and sampled every 3rd month during one year. We describe the structure of inter-individual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited markers of poor metabolic health suggestive of a functional link between metabolic and immunologic homeostatic regulation. HIGHLIGHTSLongitudinal variation in immune cell composition during one year Inter-individual variation can be described along a principal curve Immune cell and protein relationships are inferred Variability over time is an individual feature correlating with markers of poor metabolic health

immunology