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A new dynamic correlation algorithm reveals novel functional aspects in single cell and bulk RNA-seq data

机译:一种新的动态相关算法揭示了单细胞和大量RNA-seq数据中的新功能方面

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摘要

Dynamic correlations are pervasive in high-throughput data. Large numbers of gene pairs can change their correlation patterns in response to observed/unobserved changes in physiological states. Finding changes in correlation patterns can reveal important regulatory mechanisms. Currently there is no method that can effectively detect global dynamic correlation patterns in a dataset. Given the challenging nature of the problem, the currently available methods use genes as surrogate measurements of physiological states, which cannot faithfully represent true underlying biological signals. In this study we develop a new method that directly identifies strong latent dynamic correlation signals from the data matrix, named DCA: Dynamic Correlation Analysis. At the center of the method is a new metric for the identification of pairs of variables that are highly likely to be dynamically correlated, without knowing the underlying physiological states that govern the dynamic correlation. We validate the performance of the method with extensive simulations. We applied the method to three real datasets: a single cell RNA-seq dataset, a bulk RNA-seq dataset, and a microarray gene expression dataset. In all three datasets, the method reveals novel latent factors with clear biological meaning, bringing new insights into the data.
机译:动态关联普遍存在于高通量数据中。大量基因对可以响应于生理状态中观察到/未观察到的变化而改变其相关模式。发现相关模式的变化可以揭示重要的调控机制。当前,没有一种方法可以有效地检测数据集中的全局动态相关模式。考虑到问题具有挑战性的性质,当前可用的方法使用基因作为生理状态的替代度量,无法忠实地代表真实的基础生物学信号。在这项研究中,我们开发了一种直接从数据矩阵中识别强潜在动态相关信号的新方法,称为DCA:动态相关分析。该方法的中心是一种新的度量标准,用于识别高度可能动态关联的变量对,而无需知道控制动态关联的基础生理状态。我们通过广泛的仿真验证了该方法的性能。我们将该方法应用于三个真实的数据集:单细胞RNA-seq数据集,大量RNA-seq数据集和微阵列基因表达数据集。在所有三个数据集中,该方法揭示了具有明显生物学意义的新颖潜在因子,为数据带来了新见解。

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