A biology-driven deep generative model for cell-type annotation in cytometry

Author:

Blampey Quentin1ORCID,Bercovici Nadège23ORCID,Dutertre Charles-Antoine4ORCID,Pic Isabelle2,Ribeiro Joana Mourato25ORCID,André Fabrice25ORCID,Cournède Paul-Henry1ORCID

Affiliation:

1. Université Paris-Saclay, CentraleSupélec, Laboratory of Mathematics and Computer Science (MICS) , 3 rue Joliot Curie, 91190,Gif-sur-Yvette , France

2. Université Paris-Saclay, Gustave Roussy , Inserm U981, 114 Rue Edouard Vaillant, 94805, Villejuif , France

3. Université Paris Cité, Institut Cochin , CNRS, Inserm, 22 Rue Méchain, 75014, Paris , France

4. Université Paris-Saclay, Gustave Roussy , Inserm U1015, 114 Rue Edouard Vaillant, 94805, Villejuif , France

5. Gustave Roussy, Département de Médecine Oncologique , 114 Rue Edouard Vaillant, 94805, Villejuif , France

Abstract

Abstract Cytometry enables precise single-cell phenotyping within heterogeneous populations. These cell types are traditionally annotated via manual gating, but this method lacks reproducibility and sensitivity to batch effect. Also, the most recent cytometers—spectral flow or mass cytometers—create rich and high-dimensional data whose analysis via manual gating becomes challenging and time-consuming. To tackle these limitations, we introduce Scyan https://github.com/MICS-Lab/scyan, a Single-cell Cytometry Annotation Network that automatically annotates cell types using only prior expert knowledge about the cytometry panel. For this, it uses a normalizing flow—a type of deep generative model—that maps protein expressions into a biologically relevant latent space. We demonstrate that Scyan significantly outperforms the related state-of-the-art models on multiple public datasets while being faster and interpretable. In addition, Scyan overcomes several complementary tasks, such as batch-effect correction, debarcoding and population discovery. Overall, this model accelerates and eases cell population characterization, quantification and discovery in cytometry.

Funder

Prism – National Precision Medicine Center in Oncology

French National Research Agency

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Information Systems

Reference39 articles.

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2. Mass cytometry: single cells;Spitzer;Cell,2016

3. Flow cytometry: an overview;McKinnon;Curr Protoc Immunol,2018

4. Mass cytometry: blessed with the curse of dimensionality;Newell;Nat Immunol,2016

5. Guidelines for Gating Flow Cytometry Data for Immunological Assays;Staats,2019

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