Modeling dynamic correlation in zero-inflated bivariate count data with applications to single-cell RNA sequencing data.
Modeling dynamic correlation in zero-inflated bivariate count data with applications to single-cell RNA sequencing data.
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作者：
Yang Z;Ho YY
细胞中生物分子之间的相互作用是紧密协调的，通常是高度动态的。由于这些不同的信号传导活动，经常可以观察到基因共表达模式的变化。下一代测序技术的进步为研究基因共表达的这些动态变化带来了新的统计挑战。近年来，已经开发了从单个细胞检查基因组信息的方法。单细胞RNA测序（scRNA-seq）数据是基于计数的，通常表现出过度分散和零膨胀等特征。为了探索scRNA-seq数据和其他零膨胀计数数据中的动态依赖结构，需要新的方法。在本文中，我们考虑过度分散和零通货膨胀的计数结果，并提出了一个零通货膨胀负二项动态相关模型（ZENCO）。观察到的计数数据被建模为两个组件的混合物：成功扩增和ZENCO中的丢失事件。将潜在变量并入ZENCO以模拟协变量依赖的相关性结构。我们进行模拟研究，以评估我们所提出的方法的性能，并将其与现有的方法进行比较。我们还使用来自黑色素瘤微小残留病研究的scRNA-seq数据说明了我们提出的方法的实施。
Interactions between biological molecules in a cell are tightly coordinated and often highly dynamic. As a result of these varying signaling activities, changes in gene coexpression patterns could often be observed. The advancements in next‐generation sequencing technologies bring new statistical challenges for studying these dynamic changes of gene coexpression. In recent years, methods have been developed to examine genomic information from individual cells. Single‐cell RNA sequencing (scRNA‐seq) data are count‐based, and often exhibit characteristics such as overdispersion and zero inflation. To explore the dynamic dependence structure in scRNA‐seq data and other zero‐inflated count data, new approaches are needed. In this paper, we consider overdispersion and zero inflation in count outcomes and propose a ZEro‐inflated negative binomial dynamic COrrelation model (ZENCO). The observed count data are modeled as a mixture of two components: success amplifications and dropout events in ZENCO. A latent variable is incorporated into ZENCO to model the covariate‐dependent correlation structure. We conduct simulation studies to evaluate the performance of our proposed method and to compare it with existing approaches. We also illustrate the implementation of our proposed approach using scRNA‐seq data from a study of minimal residual disease in melanoma.
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