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- Dodig-Crnkovic, Tea, et al.
(författare)
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Facets of individual-specific health signatures determined from longitudinal plasma proteome profiling
- 2020
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Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 57
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Tidskriftsartikel (refereegranskat)abstract
- 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 that 49% of the protein profiles were stable over one year. We also identified eight networks of proteins in which 11-242 proteins covaried over time. For each participant, there were unique protein profiles of which some could be explained by associations to genetic variants. Interpretation: This observational and non-interventional study identifyed noticeable diversity among clinically healthy subjects, and facets of individual-specific signatures emerged by monitoring the variability of the circulating proteomes over time. To enable more personal hence precise assessments of health states, longitudinal profiling of circulating proteomes can provide a valuable component for precision medicine approaches.
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| 2. |
- Uhlén, Mathias, et al.
(författare)
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The human secretome
- 2019
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609
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Tidskriftsartikel (refereegranskat)abstract
- The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
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| 3. |
- Zhong, Wen, et al.
(författare)
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Whole-genome sequence association analysis of blood proteins in a longitudinal wellness cohort
- 2020
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The human plasma proteome is important for many biological processes and targets for diagnostics and therapy. It is therefore of great interest to understand the interplay of genetic and environmental factors to determine the specific protein levels in individuals and to gain a deeper insight of the importance of genetic architecture related to the individual variability of plasma levels of proteins during adult life. Methods We have combined whole-genome sequencing, multiplex plasma protein profiling, and extensive clinical phenotyping in a longitudinal 2-year wellness study of 101 healthy individuals with repeated sampling. Analyses of genetic and non-genetic associations related to the variability of blood levels of proteins in these individuals were performed. Results The analyses showed that each individual has a unique protein profile, and we report on the intra-individual as well as inter-individual variation for 794 plasma proteins. A genome-wide association study (GWAS) using 7.3 million genetic variants identified by whole-genome sequencing revealed 144 independent variants across 107 proteins that showed strong association (P < 6 x 10(-11)) between genetics and the inter-individual variability on protein levels. Many proteins not reported before were identified (67 out of 107) with individual plasma level affected by genetics. Our longitudinal analysis further demonstrates that these levels are stable during the 2-year study period. The variability of protein profiles as a consequence of environmental factors was also analyzed with focus on the effects of weight loss and infections. Conclusions We show that the adult blood levels of many proteins are determined at birth by genetics, which is important for efforts aimed to understand the relationship between plasma proteome profiles and human biology and disease.
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