Hummel Manuela, Meister Reinhard, Mansmann Ulrich
IBE, University of Munich, Technische Fachhochschule Berlin and Department of Statistics, University of Munich, Germany.
Bioinformatics. 2008 Jan 1;24(1):78-85. doi: 10.1093/bioinformatics/btm531. Epub 2007 Nov 17.
Several authors have studied expression in gene sets with specific goals: overrepresentation of interesting genes in functional groups, predictive power for class membership and searches for groups where the constituent genes show coordinated changes in expression under the experimental conditions. The purpose of this article is to follow the third direction. One important aspect is that the gene sets under analysis are known a priori and are not determined from the experimental data at hand. Our goal is to provide a methodology that helps to identify the relevant structural constituents (phenotypical, experimental design, biological component) that determine gene expression in a group.
Gene-wise linear models are used to formalize the structural aspects of a study. The full model is contrasted with a reduced model that lacks the relevant design component. A comparison with respect to goodness of fit is made and quantified. An asymptotic test and a permutation test are derived to test the null hypothesis that the reduced model sufficiently explains the observed expression within the gene group of interest. Graphical tools are available to illustrate and interpret the results of the analysis. Examples demonstrate the wide range of application.
The R-package GlobalAncova (http://www.bioconductor.org) offers data and functions as well as a vignette to guide the user through specific analysis steps.
几位作者研究了具有特定目标的基因集表达：功能组中有趣基因的过度表达、类别成员的预测能力以及寻找在实验条件下组成基因表达呈现协调变化的组。本文的目的是遵循第三个方向。一个重要方面是所分析的基因集是先验已知的，并非从手头的实验数据中确定。我们的目标是提供一种方法，有助于识别决定一组基因表达的相关结构成分（表型、实验设计、生物成分）。
基因层面的线性模型用于将研究的结构方面形式化。完整模型与缺少相关设计成分的简化模型进行对比。对拟合优度进行比较并量化。推导出渐近检验和置换检验，以检验简化模型是否足以解释感兴趣基因组内观察到的表达这一原假设。提供了图形工具来阐明和解释分析结果。示例展示了广泛的应用范围。
R包GlobalAncova（http://www.bioconductor.org）提供数据、函数以及一个小插图，以指导用户完成特定的分析步骤。
