Department of Molecular Genetics, University of Toronto, Ontario, Canada.
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Ontario, Canada.
PLoS Comput Biol. 2020 Sep 9;16(9):e1008205. doi: 10.1371/journal.pcbi.1008205. eCollection 2020 Sep.
Single-cell RNA sequencing (scRNA-seq) can map cell types, states and transitions during dynamic biological processes such as tissue development and regeneration. Many trajectory inference methods have been developed to order cells by their progression through a dynamic process. However, when time series data is available, most of these methods do not consider the available time information when ordering cells and are instead designed to work only on a single scRNA-seq data snapshot. We present Tempora, a novel cell trajectory inference method that orders cells using time information from time-series scRNA-seq data. In performance comparison tests, Tempora inferred known developmental lineages from three diverse tissue development time series data sets, beating state of the art methods in accuracy and speed. Tempora works at the level of cell clusters (types) and uses biological pathway information to help identify cell type relationships. This approach increases gene expression signal from single cells, processing speed, and interpretability of the inferred trajectory. Our results demonstrate the utility of a combination of time and pathway information to supervise trajectory inference for scRNA-seq based analysis.
单细胞 RNA 测序 (scRNA-seq) 可绘制动态生物学过程(如组织发育和再生)中的细胞类型、状态和转变。已经开发出许多轨迹推断方法来根据细胞在动态过程中的进展对其进行排序。然而,当有时间序列数据时,这些方法中的大多数在对细胞进行排序时并不考虑可用的时间信息,而是专门设计用于仅在单个 scRNA-seq 数据快照上运行。我们提出了 Tempora,这是一种新颖的细胞轨迹推断方法,它使用来自时间序列 scRNA-seq 数据的时间信息对细胞进行排序。在性能比较测试中,Tempora 从三个不同的组织发育时间序列数据集推断出已知的发育谱系,在准确性和速度方面均优于最先进的方法。Tempora 在细胞群(类型)的层面上运行,并使用生物途径信息来帮助识别细胞类型关系。这种方法增加了单细胞的基因表达信号、处理速度和推断轨迹的可解释性。我们的结果表明,将时间和途径信息相结合来监督基于 scRNA-seq 的分析中的轨迹推断具有实用性。