Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
Department of Biology, Technion - Israel Institute of Technology, Technion City, Haifa, Israel.
Nat Rev Genet. 2022 Jun;23(6):355-368. doi: 10.1038/s41576-021-00444-7. Epub 2022 Jan 31.
Methods for profiling genes at the single-cell level have revolutionized our ability to study several biological processes and systems including development, differentiation, response programmes and disease progression. In many of these studies, cells are profiled over time in order to infer dynamic changes in cell states and types, sets of expressed genes, active pathways and key regulators. However, time-series single-cell RNA sequencing (scRNA-seq) also raises several new analysis and modelling issues. These issues range from determining when and how deep to profile cells, linking cells within and between time points, learning continuous trajectories, and integrating bulk and single-cell data for reconstructing models of dynamic networks. In this Review, we discuss several approaches for the analysis and modelling of time-series scRNA-seq, highlighting their steps, key assumptions, and the types of data and biological questions they are most appropriate for.
单细胞水平基因分析方法的出现极大地提高了我们研究包括发育、分化、应答程序和疾病进展等多个生物学过程和系统的能力。在这些研究中,细胞会随着时间的推移进行分析,以推断细胞状态和类型、表达基因集、活性途径和关键调控因子的动态变化。然而,时间序列单细胞 RNA 测序(scRNA-seq)也提出了一些新的分析和建模问题。这些问题包括确定何时以及如何深入分析细胞,连接时间点内和时间点之间的细胞,学习连续轨迹,以及整合批量和单细胞数据以重建动态网络模型。在这篇综述中,我们讨论了几种分析和建模时间序列 scRNA-seq 的方法,强调了它们的步骤、关键假设以及最适合它们的数据集和生物学问题的类型。