Automated assignment of cell identity from single-cell multiplexed imaging and proteomic data.

Journal: Cell systems
Published Date:

Abstract

A major challenge in the analysis of highly multiplexed imaging data is the assignment of cells to a priori known cell types. Existing approaches typically solve this by clustering cells followed by manual annotation. However, these often require several subjective choices and cannot explicitly assign cells to an uncharacterized type. To help address these issues we present Astir, a probabilistic model to assign cells to cell types by integrating prior knowledge of marker proteins. Astir uses deep recognition neural networks for fast inference, allowing for annotations at the million-cell scale in the absence of a previously annotated reference. We apply Astir to over 2.4 million cells from suspension and imaging datasets and demonstrate its scalability, robustness to sample composition, and interpretable uncertainty estimates. We envision deployment of Astir either for a first broad cell type assignment or to accurately annotate cells that may serve as biomarkers in multiple disease contexts. A record of this paper's transparent peer review process is included in the supplemental information.

Authors

  • Michael J Geuenich
    Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Jinyu Hou
    Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5T 3A1, Canada.
  • Sunyun Lee
    Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5T 3A1, Canada.
  • Shanza Ayub
    Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Hartland W Jackson
    Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Ontario Institute of Cancer Research, Toronto, ON M5G 1M1, Canada.
  • Kieran R Campbell
    Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Statistical Sciences, University of Toronto, Toronto, ON M5S 3G3, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5T 3A1, Canada; Ontario Institute of Cancer Research, Toronto, ON M5G 1M1, Canada; Vector Institute, Toronto, ON M5G 1M1, Canada. Electronic address: kierancampbell@lunenfeld.ca.