Pan-cancer classification of single cells in the tumour microenvironment

Ido Nofech-Mozes, David Soave, Philip Awadalla () and Sagi Abelson ()
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Ido Nofech-Mozes: Ontario Institute for Cancer Research
David Soave: Ontario Institute for Cancer Research
Philip Awadalla: Ontario Institute for Cancer Research
Sagi Abelson: Ontario Institute for Cancer Research

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Single-cell RNA sequencing can reveal valuable insights into cellular heterogeneity within tumour microenvironments (TMEs), paving the way for a deep understanding of cellular mechanisms contributing to cancer. However, high heterogeneity among the same cancer types and low transcriptomic variation in immune cell subsets present challenges for accurate, high-resolution confirmation of cells’ identities. Here we present scATOMIC; a modular annotation tool for malignant and non-malignant cells. We trained scATOMIC on >300,000 cancer, immune, and stromal cells defining a pan-cancer reference across 19 common cancers and employ a hierarchical approach, outperforming current classification methods. We extensively confirm scATOMIC’s accuracy on 225 tumour biopsies encompassing >350,000 cancer and a variety of TME cells. Lastly, we demonstrate scATOMIC’s practical significance to accurately subset breast cancers into clinically relevant subtypes and predict tumours’ primary origin across metastatic cancers. Our approach represents a broadly applicable strategy to analyse multicellular cancer TMEs.

Date: 2023
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DOI: 10.1038/s41467-023-37353-8

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