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. 2015 Oct;12(10):947-950.
doi: 10.1038/nmeth.3549. Epub 2015 Aug 24.

Oscope identifies oscillatory genes in unsynchronized single-cell RNA-seq experiments

Ning Leng #  1   2 , Li-Fang Chu #  2 , Chris Barry  2 , Yuan Li  1 , Jeea Choi  1 , Xiaomao Li  1 , Peng Jiang  2 , Ron M Stewart  2 , James A Thomson  2   3   4 , Christina Kendziorski  5
Affiliations

Oscope identifies oscillatory genes in unsynchronized single-cell RNA-seq experiments

Ning Leng et al. Nat Methods. 2015 Oct.

Abstract

Oscillatory gene expression is fundamental to development, but technologies for monitoring expression oscillations are limited. We have developed a statistical approach called Oscope to identify and characterize the transcriptional dynamics of oscillating genes in single-cell RNA-seq data from an unsynchronized cell population. Applying Oscope to a number of data sets, we demonstrated its utility and also identified a potential artifact in the Fluidigm C1 platform.

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Figures

Figure 1
Figure 1
Overview of Oscope. (a) Shown are an oscillating gene group with two genes and corresponding cell state. (b) In an unsynchronized scRNA-seq experiment, mRNA is collected at time T from cells in varying states. t0,i and ti show cell i's oscillation start time and oscillation time, respectively. (c) The same genes and cells as in b, where cells are ordered by the genes’ oscillation times. (d) Expression for 100 unsynchronized cells. (e) Scatter plots of gene 1 vs. gene 2, which are independent of order. Cells are colored from cyan to brown following the x-axes of c and d, respectively. (f) Results of base cycle reconstruction for the 100 cells shown in d. (g) Flowchart of the Oscope pipeline (see Online Methods).
Figure 2
Figure 2
Oscope uncovers oscillatory signals in case study datasets. (a) Four genes in the time series data from Whitfield et al. 2002 with profiles ordered by Oscope; the peak of the base cycle is marked in gray. (b) The same four genes following the known order over time with the peak of the first base cycle (shown in yellow) marked in gray. (c) Four genes from a 29 gene group identified by Oscope using scRNA-seq data from 213 unlabeled hESCs. Shown are Oscope recovered profiles. (d) The same four genes ordered using 460 cells (213 unlabeled and 247 H1-Fucci cells are shown as open circles and dots, respectively). The Fucci labels (ignored prior to applying Oscope) are shown in different colors for the 247 cells. Phase boundaries defined by the reconstructed order are shown above the plots. (e) The proportion of unlabeled cells that fall into each phase defined by the boundaries in d.
Figure 3
Figure 3
Oscope uncovers dynamic signals of technical origin in scRNA-seq datasets. (a) Default plate output ID layouts of the capture sites on the C1 chip. (b) Expression of four genes with potential ordering effects. Cells are ordered by the C1 plate output ID (A01-A12, B01-B12, ..., H01-H12). Cells from the colored capture sites in a are also shown in magenta. Three replicate hESC experiments are separated by gray lines. (c) The same four genes for a data set obtained from Trapnell et al., 2014, ordered following the cell order listed in their supplementary data. The four experiments are separated by gray lines. The y-axes are limited to 98th quantile of gene-specific FPKMs for better visualization.
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