Reversed graph embedding resolves complex single-cell trajectories (original) (raw)

Nature Methods volume 14, pages 979–982 (2017)Cite this article

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Abstract

Single-cell trajectories can unveil how gene regulation governs cell fate decisions. However, learning the structure of complex trajectories with multiple branches remains a challenging computational problem. We present Monocle 2, an algorithm that uses reversed graph embedding to describe multiple fate decisions in a fully unsupervised manner. We applied Monocle 2 to two studies of blood development and found that mutations in the genes encoding key lineage transcription factors divert cells to alternative fates.

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Acknowledgements

We thank I. Tirosh for discussions on marker-based ordering, F. Theis and F.A. Wolf for discussions on the data analysis with DPT from Paul et al.9, and members of the Trapnell laboratory for comments on the manuscript. This work was supported by US National Institutes of Health (NIH) grants DP2 HD088158 (C.T.) and U54 DK107979 (C.T.); C.T. is partly supported by a Dale. F. Frey Award for Breakthrough Scientists and an Alfred P. Sloan Foundation Research Fellowship; and H.A.P. is supported by a National Science Foundation (NSF) Graduate Research Fellowship (DGE-1256082).

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Authors and Affiliations

  1. Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, USA
    Xiaojie Qiu & Cole Trapnell
  2. Department of Genome Sciences, University of Washington, Seattle, Washington, USA
    Xiaojie Qiu, Raghav Chawla, Hannah A Pliner & Cole Trapnell
  3. HERE Company, Chicago, Illinois, USA
    Qi Mao
  4. Department of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai, China
    Ying Tang
  5. Department of Mathematics, Statistics and Computer Science, University of Illinois at Chicago, Chicago, USA
    Li Wang

Authors

  1. Xiaojie Qiu
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  2. Qi Mao
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  3. Ying Tang
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  4. Li Wang
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  5. Raghav Chawla
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  6. Hannah A Pliner
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  7. Cole Trapnell
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Contributions

X.Q., Q.M., and C.T. designed and implemented Monocle 2; X.Q. performed the analysis; Y.T. and L.W. contributed to the technical design; R.C. and H.A.P. performed the testing; C.T. conceived the project; and all authors wrote the manuscript.

Corresponding author

Correspondence toCole Trapnell.

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The authors declare no competing financial interests.

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Qiu, X., Mao, Q., Tang, Y. et al. Reversed graph embedding resolves complex single-cell trajectories.Nat Methods 14, 979–982 (2017). https://doi.org/10.1038/nmeth.4402

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