论文标题
Poisson-Tweedie综合效应模型:一种灵活的方法,用于分析纵向RNA-seq数据
Poisson-Tweedie mixed-effects model: a flexible approach for the analysis of longitudinal RNA-seq data
论文作者
论文摘要
我们提出了一种用于纵向计数数据的新建模方法,该方法是由纵向RNA测序实验的可用性增加所激发的。 RNA-seq计数的分布通常表现出过度分散,零通气和沉重的尾巴。此外,在纵向设计中,来自同一受试者的重复测量通常是(正面)相关的。我们提出了一个基于泊松 - 与tweedie分布的广义线性混合模型,该模型可以灵活地处理纵向过度分散计数的上述每个特征。我们开发了一种计算方法,以准确评估提出的模型的可能性并执行最大似然估计。我们的方法是在r软件包中实现的,可以从Cran免费下载。我们评估了PTMIX在模拟数据上的性能,并向数据集提供了一个应用程序集,该数据集具有来自健康和营养不良小鼠的纵向RNA测量测量。 Poisson-Tweedie混合效应模型的适用性不仅限于纵向RNA-Seq数据,但它扩展到了任何无独立测量值的无独立测量值的情况。
We present a new modelling approach for longitudinal count data that is motivated by the increasing availability of longitudinal RNA-sequencing experiments. The distribution of RNA-seq counts typically exhibits overdispersion, zero-inflation and heavy tails; moreover, in longitudinal designs repeated measurements from the same subject are typically (positively) correlated. We propose a generalized linear mixed model based on the Poisson-Tweedie distribution that can flexibly handle each of the aforementioned features of longitudinal overdispersed counts. We develop a computational approach to accurately evaluate the likelihood of the proposed model and to perform maximum likelihood estimation. Our approach is implemented in the R package ptmixed, which can be freely downloaded from CRAN. We assess the performance of ptmixed on simulated data and we present an application to a dataset with longitudinal RNA-sequencing measurements from healthy and dystrophic mice. The applicability of the Poisson-Tweedie mixed-effects model is not restricted to longitudinal RNA-seq data, but it extends to any scenario where non-independent measurements of a discrete overdispersed response variable are available.