Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides.

Journal: Nature communications
Published Date:

Abstract

Cancer diagnosis and management depend upon the extraction of complex information from microscopy images by pathologists, which requires time-consuming expert interpretation prone to human bias. Supervised deep learning approaches have proven powerful, but are inherently limited by the cost and quality of annotations used for training. Therefore, we present Histomorphological Phenotype Learning, a self-supervised methodology requiring no labels and operating via the automatic discovery of discriminatory features in image tiles. Tiles are grouped into morphologically similar clusters which constitute an atlas of histomorphological phenotypes (HP-Atlas), revealing trajectories from benign to malignant tissue via inflammatory and reactive phenotypes. These clusters have distinct features which can be identified using orthogonal methods, linking histologic, molecular and clinical phenotypes. Applied to lung cancer, we show that they align closely with patient survival, with histopathologically recognised tumor types and growth patterns, and with transcriptomic measures of immunophenotype. These properties are maintained in a multi-cancer study.

Authors

  • Adalberto Claudio Quiros
    School of Computing Science, University of Glasgow, Glasgow, Scotland, UK.
  • Nicolas Coudray
    Applied Bioinformatics Laboratories, NYU Grossman School of Medicine, New York, NY, USA. nicolas.coudray@nyulangone.org.
  • Anna Yeaton
    Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
  • Xinyu Yang
    Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
  • Bojing Liu
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Hortense Le
    Department of Medicine, Division of Precision Medicine, NYU Grossman School of Medicine, New York, USA.
  • Luis Chiriboga
    Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
  • Afreen Karimkhan
    Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
  • Navneet Narula
    Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
  • David A Moore
    Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Christopher Y Park
    Flatiron Institute, Simons Foundation, New York, NY, USA.
  • Harvey Pass
    Department of Cardiothoracic Surgery, NYU Grossman School of Medicine, New York, NY, USA.
  • Andre L Moreira
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • John Le Quesne
    School of Cancer Sciences, University of Glasgow, Glasgow, UK; CRUK Beatson Institute, Garscube Estate, Glasgow, UK; Department of Histopathology, Queen Elizabeth University Hospital, Glasgow, UK.
  • Aristotelis Tsirigos
    Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA; Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY 10016, USA. Electronic address: aristotelis.tsirigos@nyulangone.org.
  • Ke Yuan
    Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.