Confronting false discoveries in single-cell differential expression

Jordan W. Squair, Matthieu Gautier, Claudia Kathe, Mark A. Anderson, Nicholas D. James, Thomas H. Hutson, Rémi Hudelle, Taha Qaiser, Kaya J. E. Matson, Quentin Barraud, Ariel J. Levine, Gioele La Manno, Michael A. Skinnider () and Grégoire Courtine ()
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Jordan W. Squair: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
Matthieu Gautier: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
Claudia Kathe: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
Mark A. Anderson: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
Nicholas D. James: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
Thomas H. Hutson: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
Rémi Hudelle: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
Taha Qaiser: International Collaboration on Repair Discoveries (ICORD), University of British Columbia
Kaya J. E. Matson: Spinal Circuits and Plasticity Unit, National Institute of Neurological Disorders and Stroke
Quentin Barraud: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
Ariel J. Levine: Spinal Circuits and Plasticity Unit, National Institute of Neurological Disorders and Stroke
Gioele La Manno: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
Michael A. Skinnider: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
Grégoire Courtine: Center for Neuroprosthetics and Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Differential expression analysis in single-cell transcriptomics enables the dissection of cell-type-specific responses to perturbations such as disease, trauma, or experimental manipulations. While many statistical methods are available to identify differentially expressed genes, the principles that distinguish these methods and their performance remain unclear. Here, we show that the relative performance of these methods is contingent on their ability to account for variation between biological replicates. Methods that ignore this inevitable variation are biased and prone to false discoveries. Indeed, the most widely used methods can discover hundreds of differentially expressed genes in the absence of biological differences. To exemplify these principles, we exposed true and false discoveries of differentially expressed genes in the injured mouse spinal cord.

Date: 2021
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DOI: 10.1038/s41467-021-25960-2

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