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

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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Figure 1: Overview of Oscope.
Figure 2: Oscope uncovers oscillatory signals in transcriptional profiles.
Figure 3: Oscope uncovers dynamic signals of technical origin in scRNA-seq data sets.

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Gene Expression Omnibus

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Acknowledgements

This work was supported by US National Institutes of Health grants GM102756, 4UH3TR000506 and 5U01HL099773, the Charlotte Geyer Foundation and the Morgridge Institute for Research. N.L. was supported by the Shapiro Fellowship. C.B. was supported by the Canadian Institutes of Health Research Banting Postdoctoral Fellowship. We thank M. Probasco and N. Propson for their assistance in sorting cells by FACS and J. Bolin, A. Elwell and B.K. Nguyen for the preparation and sequencing of the RNA-seq samples. We thank A. Gitter, K. Korthauer and R. Bacher for comments that helped improve the manuscript.

Author information

Authors and Affiliations

Authors

Contributions

N.L., L.-F.C., R.M.S., J.A.T. and C.K. designed research, analyzed data and wrote the manuscript; C.B. generated the H1-FUCCI cell line; Y.L., J.C. and X.L. contributed to the simulation studies; and P.J. performed RNA-seq read mapping, quantification and quality control.

Corresponding author

Correspondence to Christina Kendziorski.

Ethics declarations

Competing interests

J.A.T. is a founder, stockholder, consultant and board member of Cellular Dynamics International (CDI).

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–16, Supplementary Table 1 and Supplementary Note (PDF 2605 kb)

Supplementary Table 2

Cell cycle cluster identified in H1 hESC data (XLSX 30 kb)

Supplementary Table 3

Ordering effect cluster identified in H1 hESC data (XLSX 28 kb)

Supplementary Table 4

403 genes with ANOVA p-value less than 0.005 on H1 hESC data (XLSX 22 kb)

Supplementary Table 5

Whitfield et al. data with shuffled sample order (Oscope input order) (XLSX 47 kb)

Supplementary Table 6

Cell cycle cluster identified in Whitfield data (XLSX 37 kb)

Supplementary Table 7

Oscope recovered order on Whitfield data using the cell cycle cluster (XLSX 30 kb)

Supplementary Table 8

2376 genes with high mean high variance in H1 hESC data (XLSX 62 kb)

Supplementary Table 9

Oscope recovered order on H1 data using the cell cycle cluster (XLSX 37 kb)

Supplementary Table 10

Oscope recovered order on H1 and H1-Fucci combined data using the cell cycle cluster (XLSX 42 kb)

Supplementary Table 11

Sample ID and capture site map of H1 hESC data (XLSX 41 kb)

Supplementary Software

Oscope R package and vignette (ZIP 872 kb)

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Leng, N., Chu, LF., Barry, C. et al. Oscope identifies oscillatory genes in unsynchronized single-cell RNA-seq experiments. Nat Methods 12, 947–950 (2015). https://doi.org/10.1038/nmeth.3549

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