Abstract
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.
Highlights
Dynamic tissue-level processes, such as development, aging and regeneration, are critical for multicellular organisms
Single-cell RNA sequencing enables an unparalleled ability to map the heterogeneity of dynamic multicellular processes, such as tissue development, tumor growth, wound response and repair, and inflammation
Multiple methods have been developed to order cells along a pseudotime axis that represents a trajectory through such processes using the concept that cells that are closely related in a lineage will have similar transcriptomes
Summary
Dynamic tissue-level processes, such as development, aging and regeneration, are critical for multicellular organisms. Single-cell RNA sequencing (scRNA-seq) enables us to map the range of cell types and states in these processes at cellular resolution [1]. A single scRNA-seq snapshot can be used to infer lineage relationships between cell types and states [2]. Snapshot scRNA-seq studies have been used to investigate multiple aspects of development, including the early embryo, blood, different areas of the brain and more [3]. Even though snapshot scRNA-seq can provide novel insights into development, it has recognized limits [4], including that cell populations that appear earlier or later than the sampling time cannot be studied. Time-series scRNA-seq can address some of these limits and has been increasingly applied to study tissue development, including in cerebral cortex [5], kidney [6], and heart [7]
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