Statistical methods for evaluating DNA methylation as a marker for early detection or prognosis

Statistical methods for evaluating DNA methylation as a marker for early detection or prognosis
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DOI:
10.1155/2007/308573
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发表时间:
2007-01-01
期刊:
影响因子:
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通讯作者:
Siegmund, Kimberly D.
Siegmund, Kimberly D.
中科院分区:
医学4区
文献类型:
--
作者:
Alonzo, Todd A.;Siegmund, Kimberly D.

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我们总结了标准的和新的统计方法来评估DNA甲基化标记的分类准确性。方法的选择将取决于所研究的标志物的类型(定性/定量)、标志物的数量和结果的类型(时不变/时变)。至少需要两个错误率来评估标记物的准确性:真阳性分数和假阳性分数。根据这些错误率的组合计算的关联度量,例如比值比或相对风险,不能提供分类准确性的信息。我们提供了一个DNA甲基化标志物的例子,它与死亡时间密切相关(logrank p = 0.0003),这不是一个很好的分类器,通过真阳性和假阳性分数进行评估。最后,我们要强调研究设计的重要性。标记在不同的个体群体中表现不同。重要的是要知道哪些因素可能影响标记的准确性,以及在哪些亚群中标记可能更准确。当比较两组受试者的标记准确性时,这种理解是极其重要的。
We summarize standard and novel statistical methods for evaluating the classification accuracy of DNA methylation markers. The choice of method will depend on the type of marker studied (qualitative/quantitative), the number of markers, and the type of outcome (time-invariant/time-varying). A minimum of two error rates are needed for assessing marker accuracy: the true-positive fraction and the false-positive fraction. Measures of association that are computed from the combination of these error rates, such as the odds ratio or relative risk, are not informative about classification accuracy. We provide an example of a DNA methylation marker that is strongly associated with time to death (logrank p = 0.0003) that is not a good classifier as evaluated by the true-positive and false-positive fractions. Finally, we would like to emphasize the importance of study design. Markers can behave differently in different groups of individuals. It is important to know what factors may affect the accuracy of a marker and in which subpopulations the marker may be more accurate. Such an understanding is extremely important when comparing marker accuracy in two groups of subjects.