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

A database of tissue-specific rhythmically expressed human genes has potential applications in circadian medicine.
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DOI:
10.1126/scitranslmed.aat8806
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发表时间:
2018-09-12
影响因子:
17.1
通讯作者:
Hogenesch JB
Hogenesch JB
中科院分区:
医学1区
文献类型:
--
作者:
Ruben MD;Wu G;Smith DF;Schmidt RE;Francey LJ;Lee YY;Anafi RC;Hogenesch JB

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哺乳动物蛋白质编码基因组的一半受生物钟调节,这一发现对医学有明确的意义。最近的研究表明,生物钟影响人类心脏病和癌症的治疗结果。然而,临床上很少考虑生物时间。一个关键的障碍是缺乏人体组织特异性分子节律的信息。我们已经应用了周期性结构(CYCLOPS)算法,旨在重建样本的时间顺序,在没有时间的信息,从632人供体的13个组织的基因表达收集的循环排序。我们确定了整个身体的基因表达节律;近一半的蛋白质编码基因在分析的13个组织中至少有一个组织中循环。这些循环基因中有一千个编码蛋白质,这些蛋白质要么运输或代谢药物,要么本身就是药物靶点。这些结果为研究生理节律在医学中的作用提供了有用的资源,并支持生物时间可能在决定药物反应中发挥作用的观点。
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.
DOI: 10.1073/pnas.1619320114
发表时间: 2017-05-16
影响因子: 11.1
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发表时间: 2010-10
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