Brief Communication | Published:

chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data

Nature Methods volume 14, pages 975978 (2017) | Download Citation

Abstract

Single-cell ATAC-seq (scATAC) yields sparse data that make conventional analysis challenging. We developed chromVAR (http://www.github.com/GreenleafLab/chromVAR), an R package for analyzing sparse chromatin-accessibility data by estimating gain or loss of accessibility within peaks sharing the same motif or annotation while controlling for technical biases. chromVAR enables accurate clustering of scATAC-seq profiles and characterization of known and de novo sequence motifs associated with variation in chromatin accessibility.

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Acknowledgements

This work was supported by National Institutes of Health (NIH) P50HG007735 (to W.J.G.), U19AI057266 (to W.J.G.) HG00943601 (to W.J.G.), the Rita Allen Foundation (to W.J.G.), and the Baxter Foundation Faculty Scholar Grant and the Human Frontiers Science Program (to W.J.G). W.J.G. is a Chan Zuckerberg Biohub investigator. J.D.B. acknowledges support from the Harvard Society of Fellows and Broad Institute Fellowship. A.N.S. acknowledges support from the National Science Foundation (NSF) GRFP (DGE-114747). We thank C. Lareau for valuable suggestions for improvements on the package as well as members of the Greenleaf and Buenrostro labs for useful discussions.

Author information

Affiliations

  1. Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.

    • Alicia N Schep
    • , Beijing Wu
    •  & William J Greenleaf
  2. Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.

    • Alicia N Schep
    • , Beijing Wu
    •  & William J Greenleaf
  3. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Jason D Buenrostro
  4. Harvard Society of Fellows, Harvard University, Cambridge, Massachusetts, USA.

    • Jason D Buenrostro
  5. Department of Applied Physics, Stanford University, Stanford, California, USA.

    • William J Greenleaf
  6. Chan Zuckerberg Biohub, San Francisco, California, USA.

    • William J Greenleaf

Authors

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Contributions

A.N.S., J.D.B., and W.J.G. conceived the project and wrote the manuscript. A.N.S. wrote the chromVAR R package and performed the analyses with input from J.D.B. and W.J.G. B.W. generated the scATAC-seq data.

Competing interests

J.D.B. and W.J.G. are listed as inventors on a patent (PCT/US2014/038825) for the ATAC- seq method. W.J.G. is a scientific cofounder of Epinomics.

Corresponding authors

Correspondence to Jason D Buenrostro or William J Greenleaf.

Integrated supplementary information

Supplementary information

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  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–15 and Supplementary Notes 1–4.

  2. 2.

    Life Sciences Reporting Summary

    Life Sciences Reporting Summary.

Zip files

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    Supplementary Software 1

    ChromVar software. See www.github.com/GreenleafLab/chromVAR for version updates.

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DOI

https://doi.org/10.1038/nmeth.4401

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