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

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          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.

          Funding

          This work was supported by the Erling Persson Foundation, the Swedish Heart and Lung Foundation, the Knut and Alice Wallenberg Foundation, Science for Life Laboratory, and the Swedish Research Council.

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          Most cited references 38

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          Proteomics. Tissue-based map of the human proteome.

          Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. Copyright © 2015, American Association for the Advancement of Science.
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            The Genotype-Tissue Expression (GTEx) project.

            Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
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              A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research.

               Mae Li,  Terry Koo (2016)
              Intraclass correlation coefficient (ICC) is a widely used reliability index in test-retest, intrarater, and interrater reliability analyses. This article introduces the basic concept of ICC in the content of reliability analysis.
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                Author and article information

                Contributors
                Journal
                EBioMedicine
                EBioMedicine
                EBioMedicine
                Elsevier
                2352-3964
                03 July 2020
                July 2020
                03 July 2020
                : 57
                Affiliations
                [a ]Science for Life Laboratory, Department of Protein Science, KTH-Royal Institute of Technology, Tomtebodavägen 23, Stockholm 171 65, Sweden
                [b ]Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
                [c ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, Stockholm 171 77, Sweden
                [d ]Center for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden
                [e ]Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT the Arctic University of Norway, Tromsø 9010, Norway
                [f ]Coagulation unit, Department of Hematology, Karolinska University Hospital, Stockholm 171 76, Sweden
                [g ]Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg 413 45, Sweden
                [h ]Region Västra Götaland, Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden
                [i ]Region Västra Götaland, Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden
                [j ]Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby 2800, Denmark
                Author notes
                [* ]Corresponding author. jochen.schwenk@ 123456scilifelab.se
                Article
                S2352-3964(20)30229-2 102854
                10.1016/j.ebiom.2020.102854
                7334812
                32629387
                © 2020 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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