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Sci Transl Med. 2018 Sep 12;10(458). pii: eaat8806. doi: 10.1126/scitranslmed.aat8806.

A database of tissue-specific rhythmically expressed human genes has potential applications in circadian medicine.

Author information

1
Divisions of Human Genetics and Immunobiology, Center for Chronobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229, USA.
2
Divisions of Pediatric Otolaryngology and Pulmonary and Sleep Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
3
Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati School of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
4
Department of Medicine, Center for Sleep and Circadian Neurobiology, Institute for Biomedical Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
5
Divisions of Human Genetics and Immunobiology, Center for Chronobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229, USA. john.hogenesch@cchmc.org.

Abstract

The discovery that half of the mammalian protein-coding genome is regulated by the circadian clock has clear implications for medicine. Recent studies demonstrated that the circadian clock influences therapeutic outcomes in human heart disease and cancer. However, biological time is rarely given clinical consideration. A key barrier is the absence of information on tissue-specific molecular rhythms in the human body. We have applied the cyclic ordering by periodic structure (CYCLOPS) algorithm, designed to reconstruct sample temporal order in the absence of time-of-day information, to the gene expression collection of 13 tissues from 632 human donors. We identified rhythms in gene expression across the body; nearly half of protein-coding genes were shown to be cycling in at least 1 of the 13 tissues analyzed. One thousand of these cycling genes encode proteins that either transport or metabolize drugs or are themselves drug targets. These results provide a useful resource for studying the role of circadian rhythms in medicine and support the idea that biological time might play a role in determining drug response.

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