使用 Scribe 从耦合的单细胞表达动力学推断因果基因调控网络。
Inferring Causal Gene Regulatory Networks from Coupled Single-Cell Expression Dynamics Using Scribe.
机构信息
Molecular & Cellular Biology Program, University of Washington, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Department of Electrical Engineering, University of Washington, Seattle, WA, USA.
出版信息
Cell Syst. 2020 Mar 25;10(3):265-274.e11. doi: 10.1016/j.cels.2020.02.003. Epub 2020 Mar 4.
Here, we present Scribe (https://github.com/aristoteleo/Scribe-py), a toolkit for detecting and visualizing causal regulatory interactions between genes and explore the potential for single-cell experiments to power network reconstruction. Scribe employs restricted directed information to determine causality by estimating the strength of information transferred from a potential regulator to its downstream target. We apply Scribe and other leading approaches for causal network reconstruction to several types of single-cell measurements and show that there is a dramatic drop in performance for "pseudotime"-ordered single-cell data compared with true time-series data. We demonstrate that performing causal inference requires temporal coupling between measurements. We show that methods such as "RNA velocity" restore some degree of coupling through an analysis of chromaffin cell fate commitment. These analyses highlight a shortcoming in experimental and computational methods for analyzing gene regulation at single-cell resolution and suggest ways of overcoming it.
在这里,我们介绍 Scribe(https://github.com/aristoteleo/Scribe-py),这是一个用于检测和可视化基因之间因果调控相互作用的工具包,并探索单细胞实验在网络重建方面的潜力。Scribe 使用受限的有向信息通过估计潜在调节剂与其下游靶标之间传递的信息的强度来确定因果关系。我们将 Scribe 和其他用于因果网络重建的领先方法应用于几种类型的单细胞测量,并表明与真实时间序列数据相比,“伪时间”有序的单细胞数据的性能有显著下降。我们证明了进行因果推断需要测量之间的时间耦合。我们通过对嗜铬细胞命运决定的分析表明,像“RNA 速度”这样的方法通过分析恢复了一定程度的耦合。这些分析突出了在单细胞分辨率分析基因调控的实验和计算方法中的一个缺点,并提出了克服该缺点的方法。
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