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arXiv 1304.4448stat.AP
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多元连续和离散纵向数据的聚类

Clustering for multivariate continuous and discrete longitudinal data

Arnošt Komárek, Lenka Komárková

摘要:

在纵向研究和常规临床随访期间,通常会收集受试者的多个连续和离散结局。为了激励我们的工作,我们考虑对原发性胆汁性肝硬化(PBC)患者进行纵向研究,这些患者具有连续的胆红素水平、离散的血小板计数和血管畸形的二分指征,作为这种纵向结果的例子。一个明显的要求是使用所有的结果值来将受试者分类成组(例如,在临床环境中具有相似预后的受试者组)。近年来,已经提出了许多基于纵向(或其他相关)结果的分类方法,不仅针对生物统计学等传统领域,还针对快速发展的生物信息学和许多其他领域。然而,大多数可用的方法只考虑连续性结果作为分类的基础,或者如果考虑非连续性结果,则不与其他不同性质的结果相结合。在这里,我们提出了一种统计方法,用于将受试者聚类(分类)到预先指定数量的具有先验未知特征的组中,这些组基于对不同性质的几个纵向结果的重复测量。该方法依赖于经典广义线性混合模型的多变量扩展,其中还假设随机效应为混合分布。我们基于贝叶斯规范的模型和基于模拟的马尔可夫链蒙特卡罗方法的推理。为了在实践中应用该方法,我们已经准备好了在R中使用的现成软件(http:www.R-project.org)。我们还讨论了分类中不确定性的评估,并讨论了最近提出的模型比较方法的使用-在我们的情况下选择一些集群-基于Plummer提出的惩罚后验偏差[Biostatistics 9(2008)523-539]。

英文摘要:

Multiple outcomes, both continuous and discrete, are routinely gathered on subjects in longitudinal studies and during routine clinical follow-up in general. To motivate our work, we consider a longitudinal study on patients with primary biliary cirrhosis (PBC) with a continuous bilirubin level, a discrete platelet count and a dichotomous indication of blood vessel malformations as examples of such longitudinal outcomes. An apparent requirement is to use all the outcome values to classify the subjects into groups (e.g., groups of subjects with a similar prognosis in a clinical setting). In recent years, numerous approaches have been suggested for classification based on longitudinal (or otherwise correlated) outcomes, targeting not only traditional areas like biostatistics, but also rapidly evolving bioinformatics and many others. However, most available approaches consider only continuous outcomes as a basis for classification, or if noncontinuous outcomes are considered, then not in combination with other outcomes of a different nature. Here, we propose a statistical method for clustering (classification) of subjects into a prespecified number of groups with a priori unknown characteristics on the basis of repeated measurements of several longitudinal outcomes of a different nature. This method relies on a multivariate extension of the classical generalized linear mixed model where a mixture distribution is additionally assumed for random effects. We base the inference on a Bayesian specification of the model and simulation-based Markov chain Monte Carlo methodology. To apply the method in practice, we have prepared ready-to-use software for use in R (http://www.R-project.org). We also discuss evaluation of uncertainty in the classification and also discuss usage of a recently proposed methodology for model comparison - the selection of a number of clusters in our case - based on the penalized posterior deviance proposed by Plummer [Biostatistics 9 (2008) 523-539].

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