Molecular-timetable methods for detection of body time and rhythm disorders from single-time-point genome-wide expression profiles

Molecular-timetable methods for detection of body time and rhythm disorders from single-time-point genome-wide expression profiles
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DOI:
10.1073/pnas.0401882101
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发表时间:
2004-08-03
影响因子:
11.1
通讯作者:
Hashimoto, S
Hashimoto, S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ueda, HR;Chen, WB;Hashimoto, S

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通过单时间点测定检测个体身体时间(BT)一直是医学上长期未实现的梦想,因为BT信息可以用于在给药期间最大化效力并最小化毒性,从而实现高度优化的药物治疗。为了实现这个梦想,我们创建了一个由超过100个“时间指示基因”组成的“分子时间表”,这些基因的表达水平可以代表内部BT。在这里,我们描述了一个强大的方法,称为“分子时间表法”的BT检测从一个单一的时间点的表达谱。该方法的功效通过BT的灵敏和准确检测以及节律紊乱的灵敏诊断来证明。这些结果证明了基于单时间点采样的BT检测的可行性,表明了基于表达的节律紊乱诊断的潜力,并可能将功能基因组学转化为时间治疗和个性化医疗。
Detection of individual body time (BT) via a single-time-point assay has been a longstanding unfulfilled dream in medicine, because BT information can be exploited to maximize potency and minimize toxicity during drug administration and thus will enable highly optimized medication. To achieve this dream, we created a "molecular timetable" composed of >100 "time-indicating genes," whose gene expression levels can represent internal BT. Here we describe a robust method called the "molecular-timetable method" for BT detection from a single-time-point expression profile. The power of this method is demonstrated by the sensitive and accurate detection of BT and the sensitive diagnosis of rhythm disorders. These results demonstrate the feasibility of BT detection based on single-time-point sampling, suggest the potential for expression-based diagnosis of rhythm disorders, and may translate functional genomics into chronotherapy and personalized medicine.