Reversed graph embedding resolves complex single-cell trajectories

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. Access through your

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FOR ANALYZING COMPLEX HIERARCHIES IN SINGLE-CELL DATA Article Open access 11 June 2020 LINEAGEOT IS A UNIFIED FRAMEWORK FOR LINEAGE TRACING AND TRAJECTORY INFERENCE Article Open access 16

August 2021 DECIPHERING DRIVER REGULATORS OF CELL FATE DECISIONS FROM SINGLE-CELL TRANSCRIPTOMICS DATA WITH CEFCON Article Open access 20 December 2023 ACCESSION CODES PRIMARY ACCESSIONS

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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 AUTHORS AND

AFFILIATIONS * Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, USA Xiaojie Qiu & Cole Trapnell * Department of Genome Sciences, University of

Washington, Seattle, Washington, USA Xiaojie Qiu, Raghav Chawla, Hannah A Pliner & Cole Trapnell * HERE Company, Chicago, Illinois, USA Qi Mao * Department of Physics and Astronomy,

Shanghai Jiao Tong University, Shanghai, China Ying Tang * Department of Mathematics, Statistics and Computer Science, University of Illinois at Chicago, Chicago, USA Li Wang Authors *

Xiaojie Qiu View author publications You can also search for this author inPubMed Google Scholar * Qi Mao View author publications You can also search for this author inPubMed Google Scholar

* Ying Tang View author publications You can also search for this author inPubMed Google Scholar * Li Wang View author publications You can also search for this author inPubMed Google

Scholar * Raghav Chawla View author publications You can also search for this author inPubMed Google Scholar * Hannah A Pliner View author publications You can also search for this author

inPubMed Google Scholar * Cole Trapnell View author publications You can also search for this author inPubMed Google Scholar 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 to Cole Trapnell. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION

SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–20 and Supplementary Note. (PDF 20516 kb) LIFE SCIENCES REPORTING SUMMARY Life Sciences Reporting Summary. (PDF 129 kb) SUPPLEMENTARY

DATA 1 Zipped file for the neuron simulation data. (ZIP 35169 kb) SUPPLEMENTARY DATA 2 Zipped file for the least action path data. (ZIP 401 kb) SUPPLEMENTARY DATA 3 Zipped file for the

complicate tree structure data. (ZIP 3 kb) SUPPLEMENTARY SOFTWARE Software and analysis code used in this study which can reproduce all results. (ZIP 15812 kb) RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 22 February 2017 * Accepted: 20 July 2017 * Published: 21 August 2017 * Issue Date: 01 October 2017 * DOI:

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