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

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Science Translational Medicine  12 Sep 2018:
Vol. 10, Issue 458, eaat8806
DOI: 10.1126/scitranslmed.aat8806

Body timing

Although the existence of circadian clock–dependent modulation of gene expression in humans has been known for more than a decade, the relevance of the circadian clock in drug response and therapeutic outcome has been only recently appreciated. Now, Ruben et al. used an algorithm called cyclic ordering by periodic structure (CYCLOPS) to create a database of cycling genes in 13 human tissues. The authors show that several rhythmically expressed genes code for known drug targets or for proteins involved in drug transport and metabolism. The data represent a useful resource for circadian medicine and strengthen the notion that circadian rhythms should be considered when determining therapeutic interventions.


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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