Because one of the motivations for performing a single cell RNA-seq experiment is to conduct an unbiased, genome-wide study, we would like an unsupervised approach for inferring this internal clock, rather than relying on known marker genes or experiments starting from synchronized cells. To combine these snapshots into a coherent picture, we need an “internal clock” that tells, for each cell, where it is in the process. The advent of single cell RNA-seq enables the study of sequential gene expression changes by providing a set of time slices or “snapshots” from individual cells sampling different moments in the process.
Additionally, bulk RNA-seq data may blur aspects of the process because cells sampled at a given point in time may be at different points in the process. These factors make it very difficult to externally judge where a cell is in the process. However, in such cases, the precise sequence of changes is generally not known, few if any marker genes are known, and individual cells may proceed through the process at different rates. Understanding the dynamic regulation of gene expression in cells requires the study of important temporal processes, such as cell differentiation, the cell division cycle, or tumorigenesis.
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