A population-based gene expression signature of molecular clock phase from a single epidermal sample
Abstract 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 th...
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| Format: | Article |
| Language: | English |
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BMC
2020-08-01
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| Series: | Genome Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s13073-020-00768-9 |
| _version_ | 1831835808673300480 |
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| author | Gang Wu Marc D. Ruben Lauren J. Francey David F. Smith Joseph D. Sherrill John E. Oblong Kevin J. Mills John B. Hogenesch |
| author_facet | Gang Wu Marc D. Ruben Lauren J. Francey David F. Smith Joseph D. Sherrill John E. Oblong Kevin J. Mills John B. Hogenesch |
| author_sort | Gang Wu |
| collection | DOAJ |
| description | Abstract 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 ). |
| first_indexed | 2024-12-23T04:43:45Z |
| format | Article |
| id | doaj.art-5a938497a43c43a2be35eb6ccc9b276f |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-12-23T04:43:45Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-5a938497a43c43a2be35eb6ccc9b276f2022-12-21T17:59:42ZengBMCGenome Medicine1756-994X2020-08-0112111210.1186/s13073-020-00768-9A population-based gene expression signature of molecular clock phase from a single epidermal sampleGang Wu0Marc D. Ruben1Lauren J. Francey2David F. Smith3Joseph D. Sherrill4John E. Oblong5Kevin J. Mills6John B. Hogenesch7Divisions of Human Genetics and Immunobiology, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children’s Hospital Medical CenterDivisions of Human Genetics and Immunobiology, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children’s Hospital Medical CenterDivisions of Human Genetics and Immunobiology, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children’s Hospital Medical CenterDivisions of Pediatric Otolaryngology, Pulmonary Medicine, and the Sleep Center, Cincinnati Children’s Hospital Medical CenterThe Procter and Gamble Company, Mason Business CenterThe Procter and Gamble Company, Mason Business CenterThe Procter and Gamble Company, Mason Business CenterDivisions of Human Genetics and Immunobiology, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children’s Hospital Medical CenterAbstract 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 ).http://link.springer.com/article/10.1186/s13073-020-00768-9SkinDermisEpidermisCircadian medicinePopulation rhythmCircadian biomarkers |
| spellingShingle | Gang Wu Marc D. Ruben Lauren J. Francey David F. Smith Joseph D. Sherrill John E. Oblong Kevin J. Mills John B. Hogenesch A population-based gene expression signature of molecular clock phase from a single epidermal sample Genome Medicine Skin Dermis Epidermis Circadian medicine Population rhythm Circadian biomarkers |
| title | A population-based gene expression signature of molecular clock phase from a single epidermal sample |
| title_full | A population-based gene expression signature of molecular clock phase from a single epidermal sample |
| title_fullStr | A population-based gene expression signature of molecular clock phase from a single epidermal sample |
| title_full_unstemmed | A population-based gene expression signature of molecular clock phase from a single epidermal sample |
| title_short | A population-based gene expression signature of molecular clock phase from a single epidermal sample |
| title_sort | population based gene expression signature of molecular clock phase from a single epidermal sample |
| topic | Skin Dermis Epidermis Circadian medicine Population rhythm Circadian biomarkers |
| url | http://link.springer.com/article/10.1186/s13073-020-00768-9 |
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