Liu Delong, Weinberg Clarice R, Peddada Shyamal D
Biostatistics Branch, MD:A3-03, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA.
Bioinformatics. 2004 Nov 1;20(16):2521-8. doi: 10.1093/bioinformatics/bth274. Epub 2004 Apr 15.
Differing arresting agents and protocols can be used to synchronize cells in cultures to specific phases of the cell when studying cell-cycle gene expressions. Often, data derived from individual experiments are analyzed separately, since no appropriate statistical methodology is available at the moment to analyze the data from all such experiments simultaneously. The focus of this paper is to determine the association and coherence of the relative activation times of cell-cycling genes under different experimental conditions. Using a circular-circular regression model, we define two parameters, a rotation parameter for the angular difference between cells' arresting times (phases) in two cell-cycle experiments, and an association parameter to describe the correspondence between the cycle times of maximal expression (phase angles) for a set of genes studied in two experiments. Further, we propose a procedure to assess coherence across multiple experiments, i.e. to what extent the circular ordering of the phase angles of genes is maintained across multiple experiments. Coherence of genes across experiments suggests that functionally these genes tend to respond in a stereotypically sequenced way under different experimental conditions. Our proposed methodology is illustrated by applying it to a HeLa cell-cycle gene-expression data.
在研究细胞周期基因表达时，可以使用不同的细胞周期阻断剂和方案将培养中的细胞同步到细胞的特定阶段。通常，来自单个实验的数据是单独分析的，因为目前没有合适的统计方法可以同时分析所有这些实验的数据。本文的重点是确定在不同实验条件下细胞周期基因相对激活时间的关联和一致性。使用圆-圆回归模型，我们定义了两个参数，一个旋转参数用于两个细胞周期实验中细胞阻断时间（阶段）之间的角度差异，以及一个关联参数来描述在两个实验中研究的一组基因的最大表达周期时间（相位角）之间的对应关系。此外，我们提出了一种评估多个实验间一致性的程序，即基因相位角的圆形排序在多个实验中保持的程度。实验间基因的一致性表明，在功能上，这些基因在不同实验条件下倾向于以刻板的顺序做出反应。通过将我们提出的方法应用于HeLa细胞周期基因表达数据来说明该方法。
