Journal
NATURE REVIEWS GENETICS
Volume 23, Issue 6, Pages 355-368Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41576-021-00444-7
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Funding
- National Institutes of Health (NIH) [1R01GM122096, OT2OD026682, 1U54AG075931, 1U24CA268108]
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Methods for profiling genes at the single-cell level have greatly advanced our understanding of biological processes and systems. However, time-series single-cell RNA sequencing poses new challenges for analysis and modeling, including determining when and how to profile cells, linking cells across time points, learning continuous trajectories, and integrating different types of data.
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.
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