Abstract

We present SCENIC, a computational method for simultaneous gene regulatory network reconstruction and cell-state identification from single-cell RNA-seq data (http://scenic.aertslab.org). On a compendium of single-cell data from tumors and brain, we demonstrate that cis-regulatory analysis can be exploited to guide the identification of transcription factors and cell states. SCENIC provides critical biological insights into the mechanisms driving cellular heterogeneity.

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Acknowledgements

This work is funded by The Research Foundation - Flanders (FWO; grants G.0640.13 and G.0791.14 to S. Aerts; G092916N to J.-C.M.), Special Research Fund (BOF) KU Leuven (grants PF/10/016 and OT/13/103 to S. Aerts), Foundation Against Cancer (2012-F2, 2016-070 and 2015-143 to S. Aerts) and ERC Consolidator Grant (724226_cis-CONTROL to S. Aerts). S. Aibar is supported by a PDM Postdoctoral Fellowship from the KU Leuven. Z.K.A. and J.W. are supported by postdoctoral fellowships from Kom op Tegen Kanker; V.A.H.-T. is supported by the F.R.S.-FNRS Belgium; and H.I. is supported by a PhD fellowship from the agency for Innovation by Science and Technology (IWT). Funding for T.M. and J.A. is provided by Symbiosys and IMEC HI^2 Data Science. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. T.M. would like to thank J. Simm for helpful comments and suggestions regarding gradient boosting.

Author information

Affiliations

  1. VIB Center for Brain & Disease Research, Laboratory of Computational Biology, Leuven, Belgium.

    • Sara Aibar
    • , Carmen Bravo González-Blas
    • , Hana Imrichova
    • , Gert Hulselmans
    • , Zeynep Kalender Atak
    • , Jasper Wouters
    •  & Stein Aerts
  2. KU Leuven, Department of Human Genetics, Leuven, Belgium.

    • Sara Aibar
    • , Carmen Bravo González-Blas
    • , Hana Imrichova
    • , Gert Hulselmans
    • , Zeynep Kalender Atak
    • , Jasper Wouters
    •  & Stein Aerts
  3. KU Leuven ESAT/STADIUS, VDA-lab, Leuven, Belgium.

    • Thomas Moerman
    •  & Jan Aerts
  4. IMEC Smart Applications and Innovation Services, Leuven, Belgium.

    • Thomas Moerman
    •  & Jan Aerts
  5. Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium.

    • Vân Anh Huynh-Thu
    •  & Pierre Geurts
  6. VIB Center for Cancer Biology, Laboratory for Molecular Cancer Biology, Leuven, Belgium.

    • Florian Rambow
    •  & Jean-Christophe Marine
  7. KU Leuven, Department of Oncology, Leuven, Belgium.

    • Florian Rambow
    •  & Jean-Christophe Marine
  8. KU Leuven, Department of Imaging and Pathology Translational Cell and Tissue Research, Leuven, Belgium.

    • Joost van den Oord
    •  & Jasper Wouters

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Contributions

S. Aerts and S. Aibar conceived the study; S. Aibar implemented SCENIC and related packages with help of V.A.H.-T. and P.G. for GENIE3 and G.H. for RcisTarget; S. Aibar and C.B.G.-B. analyzed the data with the help of Z.K.A. and H.I.; T.M. and J.A. implemented GRNBoost; J.W. performed the IHC and knockdown experiments; F.R., J.-C.M. and J.v.d.O. contributed reagents and helped with the interpretation of the melanoma analyses; S. Aibar, J.W. and S. Aerts wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Stein Aerts.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–15 and Supplementary Note 1

  2. 2.

    Life Sciences Reporting Summary

Excel files

  1. 1.

    Supplementary Table 1

    Results of NFATC2 knock-down versus control

Zip files

  1. 1.

    Supplementary Software

    R-packages: SCENIC, GENIE3, RcisTarget, and AUCell, as available in the moment of publication. Links to the most recent version are available at http://scenic.aertslab.org.