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Reversed graph embedding resolves complex single-cell trajectories

Nature Methods volume 14, pages 979982 (2017) | Download Citation

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).

Author information

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

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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Cole Trapnell.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–20 and Supplementary Note.

  2. 2.

    Life Sciences Reporting Summary

    Life Sciences Reporting Summary.

Zip files

  1. 1.

    Supplementary Data 1

    Zipped file for the neuron simulation data.

  2. 2.

    Supplementary Data 2

    Zipped file for the least action path data.

  3. 3.

    Supplementary Data 3

    Zipped file for the complicate tree structure data.

  4. 4.

    Supplementary Software

    Software and analysis code used in this study which can reproduce all results.

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DOI

https://doi.org/10.1038/nmeth.4402

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