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Author (up) Wittenbrink, N.; Ananthasubramaniam, B.; Munch, M.; Koller, B.; Maier, B.; Weschke, C.; Bes, F.; de Zeeuw, J.; Nowozin, C.; Wahnschaffe, A.; Wisniewski, S.; Zaleska, M.; Bartok, O.; Ashwal-Fluss, R.; Lammert, H.; Herzel, H.; Hummel, M.; Kadener, S.; Kunz, D.; Kramer, A. url  doi
openurl 
  Title High-accuracy determination of internal circadian time from a single blood sample Type Journal Article
  Year 2018 Publication The Journal of Clinical Investigation Abbreviated Journal J Clin Invest  
  Volume 128 Issue 9 Pages 3826-3839  
  Keywords Human Health  
  Abstract BACKGROUND: The circadian clock is a fundamental and pervasive biological program that coordinates 24-hour rhythms in physiology, metabolism, and behavior, and it is essential to health. Whereas therapy adapted to time of day is increasingly reported to be highly successful, it needs to be personalized, since internal circadian time is different for each individual. In addition, internal time is not a stable trait, but is influenced by many factors, including genetic predisposition, age, sex, environmental light levels, and season. An easy and convenient diagnostic tool is currently missing. METHODS: To establish a validated test, we followed a 3-stage biomarker development strategy: (a) using circadian transcriptomics of blood monocytes from 12 individuals in a constant routine protocol combined with machine learning approaches, we identified biomarkers for internal time; and these biomarkers (b) were migrated to a clinically relevant gene expression profiling platform (NanoString) and (c) were externally validated using an independent study with 28 early or late chronotypes. RESULTS: We developed a highly accurate and simple assay (BodyTime) to estimate the internal circadian time in humans from a single blood sample. Our assay needs only a small set of blood-based transcript biomarkers and is as accurate as the current gold standard method, dim-light melatonin onset, at smaller monetary, time, and sample-number cost. CONCLUSION: The BodyTime assay provides a new diagnostic tool for personalization of health care according to the patient's circadian clock. FUNDING: This study was supported by the Bundesministerium fur Bildung und Forschung, Germany (FKZ: 13N13160 and 13N13162) and Intellux GmbH, Germany.  
  Address Charite Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health, Laboratory of Chronobiology, Berlin, Germany  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0021-9738 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29953415; PMCID:PMC6118629 Approved no  
  Call Number GFZ @ kyba @ Serial 2194  
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