A population-based gene expression signature of molecular clock phase from a single epidermal sample.

Autor: Wu G; Divisions of Human Genetics and Immunobiology, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH, 45229, USA., Ruben MD; Divisions of Human Genetics and Immunobiology, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH, 45229, USA., Francey LJ; Divisions of Human Genetics and Immunobiology, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH, 45229, USA., Smith DF; Divisions of Pediatric Otolaryngology, Pulmonary Medicine, and the Sleep Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.; Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA., Sherrill JD; The Procter and Gamble Company, Mason Business Center, 8700 Mason Montgomery Road, Mason, OH, 45040, USA., Oblong JE; The Procter and Gamble Company, Mason Business Center, 8700 Mason Montgomery Road, Mason, OH, 45040, USA., Mills KJ; The Procter and Gamble Company, Mason Business Center, 8700 Mason Montgomery Road, Mason, OH, 45040, USA., Hogenesch JB; Divisions of Human Genetics and Immunobiology, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH, 45229, USA. john.hogenesch@cchmc.org.
Jazyk: angličtina
Zdroj: Genome medicine [Genome Med] 2020 Aug 21; Vol. 12 (1), pp. 73. Date of Electronic Publication: 2020 Aug 21.
DOI: 10.1186/s13073-020-00768-9
Abstrakt: Background: For circadian medicine to influence health, such as when to take a drug or undergo a procedure, a biomarker of molecular clock phase is required--one that is easily measured and generalizable across a broad population. It is not clear that any circadian biomarker yet satisfies these criteria.
Methods: We analyzed 24-h molecular rhythms in human dermis and epidermis at three distinct body sites, leveraging both longitudinal (n = 20) and population (n = 154) data. We applied cyclic ordering by periodic structure (CYCLOPS) to order the population samples where biopsy time was not recorded. With CYCLOPS-predicted phases, we used ZeitZeiger to discover potential biomarkers of clock phase.
Results: Circadian clock function was strongest in the epidermis, regardless of body site. We identified a 12-gene expression signature that reported molecular clock phase to within 3 h (mean error = 2.5 h) from a single sample of epidermis--the skin's most superficial layer. This set performed well across body sites, ages, sexes, and detection platforms.
Conclusions: This research shows that the clock in epidermis is more robust than dermis regardless of body site. To encourage ongoing validation of this putative biomarker in diverse populations, diseases, and experimental designs, we developed SkinPhaser--a user-friendly app to test biomarker performance in datasets ( https://github.com/gangwug/SkinPhaser ).
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje