Multiple testing on the directed acyclic graph of gene ontology
Multiple testing on the directed acyclic graph of gene ontology
复制标题
基因本体有向无环图的多重测试
DOI：
10.1093/bioinformatics/btm628
复制
发表时间：
2008-02-15
期刊：
影响因子：
5.8
通讯作者：
Mansmann, Ulrich
中科院分区：
文献类型：
--
作者：
Goeman, Jelle J.;Mansmann, Ulrich
动机：当前的多重性调整方法在测试 GO 术语的表达谱与响应变量的关联时，没有利用基因本体（GO）的图结构。结果：我们提出了一种多重测试方法，称为焦点级别程序，它保留了基因本体（GO）的图结构。该程序是封闭测试程序与 Holm 方法的组合。它要求用户在 GO 图中选择一个“焦点级别”，该级别反映了用户最感兴趣的术语的特异性级别。此选择还决定了 GO 图中该过程具有最大功率的级别。我们证明该过程可以强有力地控制族错误率，而无需对所使用的测试统计量的联合分布进行任何额外假设。我们还提出了一种计算多重调整 P 值的算法。由于焦点级别过程保留了 GO 图的结构，因此它通常不会保留调整后 P 值中原始 P 值的顺序。
Motivation: Current methods for multiplicity adjustment do not make use of the graph structure of Gene Ontology (GO) when testing for association of expression profiles of GO terms with a response variable.Results: We propose a multiple testing method, called the focus level procedure, that preserves the graph structure of Gene Ontology (GO). The procedure is constructed as a combination of a Closed Testing procedure with Holm's method. It requires a user to choose a 'focus level' in the GO graph, which reflects the level of specificity of terms in which the user is most interested. This choice also determines the level in the GO graph at which the procedure has most power. We prove that the procedure strongly controls the family-wise error rate without any additional assumptions on the joint distribution of the test statistics used. We also present an algorithm to calculate multiplicity-adjusted P-values. Because the focus level procedure preserves the structure of the GO graph, it does not generally preserve the ordering of the raw P-values in the adjusted P-values.