Deep cell phenotyping and spatial analysis of multiplexed imaging with TRACERx-PHLEX.

Journal: Nature communications
Published Date: Jun 15, 2024

Abstract

The growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep learning-based cell segmentation (deep-imcyto), automated cell-type annotation (TYPEx) and interpretable spatial analysis (Spatial-PHLEX) as three independent but interoperable modules. PHLEX generates single-cell identities, cell densities within tissue compartments, marker positivity calls and spatial metrics such as cellular barrier scores, along with summary graphs and spatial visualisations. PHLEX was developed using imaging mass cytometry (IMC) in the TRACERx study, validated using published Co-detection by indexing (CODEX), IMC and orthogonal data and benchmarked against state-of-the-art approaches. We evaluated its use on different tissue types, tissue fixation conditions, image sizes and antibody panels. As PHLEX is an automated and containerised Nextflow pipeline, manual assessment, programming skills or pathology expertise are not essential. PHLEX offers an end-to-end solution in a growing field of highly multiplexed data and provides clinically relevant insights.

Authors

  • Alastair Magness
    Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. alastair.magness@crick.ac.uk.
  • Emma Colliver
    Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Katey S S Enfield
    Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Claudia Lee
    Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Masako Shimato
    Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Emer Daly
    Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • David A Moore
    Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Monica Sivakumar
    Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Karishma Valand
    Oncogene Biology Laboratory, The Francis Crick Institute, London, UK.
  • Dina Levi
    Flow Cytometry, The Francis Crick Institute, London, UK.
  • Crispin T Hiley
    Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Philip S Hobson
    Flow Cytometry, The Francis Crick Institute, London, UK.
  • Febe van Maldegem
    Oncogene Biology Laboratory, The Francis Crick Institute, London, UK.
  • James L Reading
    Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Sergio A Quezada
    Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Julian Downward
    Oncogene Biology Laboratory, The Francis Crick Institute, London, UK.
  • Erik Sahai
    The Francis Crick Institute, London, UK.
  • Charles Swanton
    Professor, The Francis Crick Institute, London, United Kingdom.
  • Mihaela Angelova
    Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. mihaela.angelova@crick.ac.uk.

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