Differential rhythmicity: detecting altered rhythmicity in biological data
Differential rhythmicity: detecting altered rhythmicity in biological data
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DOI：
10.1093/bioinformatics/btw309
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发表时间：
2016-09-15
期刊：
影响因子：
5.8
通讯作者：
Westermark, Pal O.
中科院分区：
文献类型：
--
作者：
Thaben, Paul F.;Westermark, Pal O.
动机：生物节律，例如由细胞周期或生物钟控制的基因表达的节律，在细胞生理学中很重要。一种常见的实验类型比较了不同条件下保存的组织或细胞或具有不同基因类型的组织或细胞的节律性。这些研究提供了对节律潜在机制和功能的洞察。结果：我们提出并基准了一套用于此类分析的统计和计算方法，这里称为差分节律性分析。这些方法检测一组测量结果中节律幅度、相位和信噪比的变化。使用这些方法，我们分别比较了在两种不同光照条件下的小鼠肝脏mRNA表达的昼夜节律：恒定黑暗和明暗循环。这项分析揭示了处于明暗循环中的小鼠普遍且可重复的幅度增加。对不同节律转录子集的进一步分析表明，免疫系统在调节环境光-暗周期到节律性转录活动中发挥作用。该方法适用于全基因组或蛋白质组的研究，并针对定义明确的零假设提供严格的P值。
Motivation: Biological rhythms, such as rhythms in gene expression controlled by the cell cycle or the circadian clock, are important in cell physiology. A common type of experiment compares rhythmicity in tissues or cells either kept under different conditions or having different genotypes. Such investigations provide insights into underlying mechanisms as well as functions of rhythms.Results: We present and benchmark a set of statistical and computational methods for this type of analysis, here termed differential rhythmicity analysis. The methods detect alterations in rhythm amplitude, phase and signal to noise ratio in one set of measurements compared to another. Using these methods, we compared circadian rhythms in liver mRNA expression in mice held under two different lighting conditions: constant darkness and light-dark cycles, respectively. This analysis revealed widespread and reproducible amplitude increases in mice kept in light-dark cycles. Further analysis of the subset of differentially rhythmic transcripts implied the immune system in mediating ambient light-dark cycles to rhythmic transcriptional activities. The methods are suitable for genome- or proteome-wide studies, and provide rigorous P values against well-defined null hypotheses.