Cell type prioritization in single-cell data.

Journal: Nature biotechnology
Published Date:

Abstract

We present Augur, a method to prioritize the cell types most responsive to biological perturbations in single-cell data. Augur employs a machine-learning framework to quantify the separability of perturbed and unperturbed cells within a high-dimensional space. We validate our method on single-cell RNA sequencing, chromatin accessibility and imaging transcriptomics datasets, and show that Augur outperforms existing methods based on differential gene expression. Augur identified the neural circuits restoring locomotion in mice following spinal cord neurostimulation.

Authors

  • Michael A Skinnider
    Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. michael.skinnider@msl.ubc.ca.
  • Jordan W Squair
    Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. jordan.squair@epfl.ch.
  • Claudia Kathe
    Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Mark A Anderson
    Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Matthieu Gautier
    Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Kaya J E Matson
    Spinal Circuits and Plasticity Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
  • Marco Milano
    Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Thomas H Hutson
    Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Quentin Barraud
    Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Aaron A Phillips
    Departments of Physiology and Pharmacology, Clinical Neurosciences, and Cardiac Sciences, Hotchkiss Brain Institute and Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Alberta, Canada.
  • Leonard J Foster
    Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
  • Gioele La Manno
    Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Ariel J Levine
    Spinal Circuits and Plasticity Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
  • Grégoire Courtine