Statistical resynchronization and Bayesian detection of periodically expressed genes
Statistical resynchronization and Bayesian detection of periodically expressed genes
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DOI：
10.1093/nar/gkh205
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发表时间：
2004-01-01
影响因子：
14.9
通讯作者：
Liu, JS
中科院分区：
文献类型：
--
作者：
Lu, X;Zhang, W;Liu, JS
我们提出了一种新的正态混合模型（PNM）来拟合细胞周期微阵列实验中周期性表达（PE）基因的转录谱。该模型产生了一种有原则的统计估计程序，与现有的启发式方法相比，该程序可以更准确地估计平均细胞周期长度和基因表达周期。所提出的程序的一个中心组成部分是根据PNM与估计的周期性参数的每个PE基因的观察到的转录谱的pronization。通过使用一个双组分混合Beta模型来近似PNM拟合残差，我们采用经验贝叶斯方法来检测PE基因。我们估计，大约三分之一的基因在酿酒酵母的基因组中可能会定期转录，并确定822基因的后验概率是PE大于0.95。在这822个基因中，有540个也在斯派曼检测的800个基因列表中。基因本体注释分析表明，这822个基因中有许多参与了细胞周期相关的重要过程、功能和组分。当匹配三个独立实验的822个重复表达谱时，观察到很少的相移，表明三种同步化方法可能在释放时将细胞带到相同的阶段。
We propose a periodic-normal mixture (PNM) model to fit transcription profiles of periodically expressed (PE) genes in cell cycle microarray experiments. The model leads to a principled statistical estimation procedure that produces more accurate estimates of the mean cell cycle length and the gene expression periodicity than existing heuristic approaches. A central component of the proposed procedure is the resynchronization of the observed transcription profile of each PE gene according to the PNM with estimated periodicity parameters. By using a two-component mixture-Beta model to approximate the PNM fitting residuals, we employ an empirical Bayes method to detect PE genes. We estimate that about one-third of the genes in the genome of Saccharomyces cerevisiae are likely to be transcribed periodically, and identify 822 genes whose posterior probabilities of being PE are greater than 0.95. Among these 822 genes, 540 are also in the list of 800 genes detected by Spellman. Gene ontology annotation analysis shows that many of the 822 genes were involved in important cell cycle-related processes, functions and components. When matching the 822 resynchronized expression profiles of three independent experiments, little phase shifts were observed, indicating that the three synchronization methods might have brought cells to the same phase at the time of release.