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Inferring time-lagged causality using the derivative of single-cell expression

By Huan-Huan Wei, Hui Lu, Hongyu Zhao

Posted 03 Feb 2021
bioRxiv DOI: 10.1101/2021.02.03.429525

Many computational methods have been developed for inferring causality among genes using cross-sectional gene expression data, such as single-cell RNA sequencing (scRNA-seq) data. However, due to the limitations of scRNA-seq technologies, time-lagged causal relationships may be missed by existing methods. In this work, we propose a method, called causal inference with time-lagged information (CITL), to infer time-lagged causal relationships from scRNA-seq data by assessing conditional independence between the changing and current expression levels of genes. CITL estimates the changing expression levels of genes by "RNA velocity". We demonstrate the accuracy and stability of CITL for inferring time-lagged causality on simulation data against other leading approaches. We have applied CITL to real scRNA data and inferred 878 pairs of time-lagged causal relationships, with many of these inferred results supported by the literature.

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