| Literature DB >> 30209245 |
Marc D Ruben1, Gang Wu1, David F Smith2,3, Robert E Schmidt1, Lauren J Francey1, Yin Yeng Lee1, Ron C Anafi4, John B Hogenesch5.
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.Entities:
Mesh:
Year: 2018 PMID: 30209245 PMCID: PMC8961342 DOI: 10.1126/scitranslmed.aat8806
Source DB: PubMed Journal: Sci Transl Med ISSN: 1946-6234 Impact factor: 17.956