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      Integration of molecular profiles in a longitudinal wellness profiling cohort

      research-article
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      Nature Communications
      Nature Publishing Group UK
      Computational biology and bioinformatics, Data integration, Molecular medicine

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          Abstract

          An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.

          Abstract

          An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, the authors sample a longitudinal wellness cohort and analyse blood molecular profiles as well as gut microbiota composition.

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          Most cited references41

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          Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy.

          Qing Jiang (2014)
          The vitamin E family consists of four tocopherols and four tocotrienols. α-Tocopherol (αT) is the predominant form of vitamin E in tissues and its deficiency leads to ataxia in humans. However, results from many clinical studies do not support a protective role of αT in disease prevention in people with adequate nutrient status. On the other hand, recent mechanistic studies indicate that other forms of vitamin E, such as γ-tocopherol (γT), δ-tocopherol, and γ-tocotrienol, have unique antioxidant and anti-inflammatory properties that are superior to those of αT in prevention and therapy against chronic diseases. These vitamin E forms scavenge reactive nitrogen species, inhibit cyclooxygenase- and 5-lipoxygenase-catalyzed eicosanoids, and suppress proinflammatory signaling such as NF-κB and STAT3/6. Unlike αT, other vitamin E forms are significantly metabolized to carboxychromanols via cytochrome P450-initiated side-chain ω-oxidation. Long-chain carboxychromanols, especially 13'-carboxychromanols, are shown to have stronger anti-inflammatory effects than unmetabolized vitamins and may therefore contribute to the beneficial effects of vitamin E forms in vivo. Consistent with mechanistic findings, animal and human studies show that γT and tocotrienols may be useful against inflammation-associated diseases. This review focuses on non-αT forms of vitamin E with respect to their metabolism, anti-inflammatory effects and mechanisms, and in vivo efficacy in preclinical models as well as human clinical intervention studies. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                linn.fagerberg@scilifelab.se
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                8 September 2020
                8 September 2020
                2020
                : 11
                : 4487
                Affiliations
                [1 ]GRID grid.5037.1, ISNI 0000000121581746, Science for Life Laboratory, Department of Protein Science, , KTH Royal Institute of Technology, ; Stockholm, Sweden
                [2 ]GRID grid.8761.8, ISNI 0000 0000 9919 9582, Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, , University of Gothenburg, ; Gothenburg, Sweden
                [3 ]GRID grid.1649.a, ISNI 000000009445082X, Region Västra Götaland, , Sahlgrenska University Hospital, Department of Clinical Genetics and Genomics, ; Gothenburg, Sweden
                [4 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Center for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, , Karolinska Institutet, ; Stockholm, Sweden
                [5 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Science for Life Laboratory, Department of Women’s and Children’s Health, , Karolinska Institutet, ; Stockholm, Sweden
                [6 ]GRID grid.12650.30, ISNI 0000 0001 1034 3451, Swedish Metabolomics Centre, Department of Molecular Biology, , Umeå University, ; 901 87 Umeå, Sweden
                [7 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, , King’s College London, ; London, UK
                [8 ]GRID grid.1649.a, ISNI 000000009445082X, Region Västra Götaland, , Sahlgrenska University Hospital, Department of Internal Medicine, ; Gothenburg, Sweden
                [9 ]GRID grid.8761.8, ISNI 0000 0000 9919 9582, Department of Molecular and Clinical Medicine, Institute of Medicine, , University of Gothenburg, ; Gothenburg, Sweden
                [10 ]GRID grid.1649.a, ISNI 000000009445082X, Region Västra Götaland, , Sahlgrenska University Hospital, Department of Cardiology, ; Gothenburg, Sweden
                [11 ]Codon Consulting, 118 26 Stockholm, Sweden
                [12 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Department of Learning, Informatics, Management and Ethics, , Karolinska Institutet, ; Stockholm, Sweden
                [13 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Department of Medical Epidemiology and Biostatistics, , Karolinska Institutet, ; Stockholm, Sweden
                [14 ]GRID grid.6341.0, ISNI 0000 0000 8578 2742, Swedish Metabolomics Centre, Department of Forest Genetics and Plant Physiology, , Swedish University of Agricultural Sciences, ; 907 36 Umeå, Sweden
                [15 ]GRID grid.1649.a, ISNI 000000009445082X, Region Västra Götaland, , Sahlgrenska University Hospital, Department of Clinical Physiology, ; Gothenburg, Sweden
                [16 ]GRID grid.5254.6, ISNI 0000 0001 0674 042X, Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, , University of Copenhagen, ; Copenhagen, Denmark
                [17 ]GRID grid.5170.3, ISNI 0000 0001 2181 8870, Center for Biosustainability, , Danish Technical University, ; Copenhagen, Denmark
                Author information
                http://orcid.org/0000-0003-0024-960X
                http://orcid.org/0000-0002-7422-6104
                http://orcid.org/0000-0001-7256-5770
                http://orcid.org/0000-0001-9730-1915
                http://orcid.org/0000-0002-3806-323X
                http://orcid.org/0000-0003-0880-5375
                http://orcid.org/0000-0002-7000-4416
                http://orcid.org/0000-0003-2261-0881
                http://orcid.org/0000-0002-2875-896X
                http://orcid.org/0000-0002-4254-6090
                http://orcid.org/0000-0002-3721-8586
                http://orcid.org/0000-0002-1161-4476
                http://orcid.org/0000-0002-9941-7855
                http://orcid.org/0000-0001-6959-7704
                http://orcid.org/0000-0003-0996-1644
                http://orcid.org/0000-0002-0017-7987
                http://orcid.org/0000-0001-8141-8449
                http://orcid.org/0000-0002-4871-8818
                http://orcid.org/0000-0003-4289-5722
                http://orcid.org/0000-0002-4858-8056
                http://orcid.org/0000-0003-0198-7137
                Article
                18148
                10.1038/s41467-020-18148-7
                7479148
                32900998
                fa134031-b53a-4315-865f-4c4b3060ee43
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 February 2020
                : 3 August 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100004063, Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation);
                Award ID: KAW 2015.0344
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100007436, Familjen Erling-Perssons Stiftelse (Erling-Persson Family Foundation);
                Funded by: Heart and Lung Foundation 254002104 and 254002107
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                computational biology and bioinformatics,data integration,molecular medicine
                Uncategorized
                computational biology and bioinformatics, data integration, molecular medicine

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