A novel mathematical method for disclosing oscillations in gene transcription: A comparative study.

A novel mathematical method for disclosing oscillations in gene transcription: A comparative study.
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DOI:
10.1371/journal.pone.0198503
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Dacso CC
Dacso CC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Antoulas AC;Zhu B;Zhang Q;York B;O'Malley BW;Dacso CC

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昼夜节律是由基因转录的周期性振荡决定的,24小时周期对光和暗的反应。这一现象在生理功能方面有广泛的影响。最近的工作揭示了基因转录的更多周期,为了揭示这些周期,我们应用了一种新的信号处理方法,称为铅笔方法,并将其与传统的参数、非参数和统计方法进行比较。方法:为了评估基因表达随时间的周期性,我们分析了来自小鼠肝脏的数据库,这些小鼠肝脏被置于12小时光照/12小时黑暗循环中。我们还分析了人工生成的信号,以识别铅笔分解和其他替代方法之间的差异。结果:铅笔分解揭示了迄今为止未预料到的基因转录振荡,周期为12小时。铅笔法在检测已知存在的24小时昼夜节律周期以及确认较短周期振荡的存在方面是可靠的。这种方法的一个关键结果是可以证明不同振荡分量的正交性。这表明了这些振荡的生物学独立性,随后通过敲除负责24小时时钟的基因证实了这一点。结论:系统识别技术可以应用于生物系统,并且可以揭示可能逃避视觉检查数据的重要特征。意义:铅笔法为基因表达的本质提供了新的见解,并揭示了除了充分研究的昼夜节律模式之外的各种振荡。这一见解为研究振荡基因表达信号对细胞发挥调节作用以影响人类疾病的新机制打开了大门。
Circadian rhythmicity, the 24-hour cycle responsive to light and dark, is determined by periodic oscillations in gene transcription. This phenomenon has broad ramifications in physiologic function. Recent work has disclosed more cycles in gene transcription, and to the uncovering of these we apply a novel signal processing methodology known as the pencil method and compare it to conventional parametric, nonparametric, and statistical methods. Methods: In order to assess periodicity of gene expression over time, we analyzed a database derived from livers of mice entrained to a 12-hour light/12-hour dark cycle. We also analyzed artificially generated signals to identify differences between the pencil decomposition and other alternative methods. Results: The pencil decomposition revealed hitherto-unsuspected oscillations in gene transcription with 12-hour periodicity. The pencil method was robust in detecting the 24-hour circadian cycle that was known to exist, as well as confirming the existence of shorter-period oscillations. A key consequence of this approach is that orthogonality of the different oscillatory components can be demonstrated. thus indicating a biological independence of these oscillations, that has been subsequently confirmed empirically by knocking out the gene responsible for the 24-hour clock. Conclusion: System identification techniques can be applied to biological systems and can uncover important characteristics that may elude visual inspection of the data. Significance: The pencil method provides new insights on the essence of gene expression and discloses a wide variety of oscillations in addition to the well-studied circadian pattern. This insight opens the door to the study of novel mechanisms by which oscillatory gene expression signals exert their regulatory effect on cells to influence human diseases.
DOI: 10.1016/j.cmet.2017.05.004
发表时间: 2017-06-06
期刊: Cell metabolism
影响因子: 29
作者:
Zhu B;Zhang Q;Pan Y;Mace EM;York B;Antoulas AC;Dacso CC;O'Malley BW
通讯作者: O'Malley BW
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发表时间: 2010-10
影响因子: 3.5
作者:
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发表时间: 2012-01-01
期刊: DEVELOPMENTS IN CONTROL THEORY TOWARDS GLOCAL CONTROL
影响因子: --
作者:
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通讯作者: Antoulas, Athanasios C.
DOI: 10.1371/journal.pgen.1000442
发表时间: 2009-04
期刊: PLoS genetics
影响因子: 4.5
作者:
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通讯作者: Hogenesch JB