Integrating spatial gene expression and breast tumour morphology via deep learning.

Journal: Nature biomedical engineering
Published Date:

Abstract

Spatial transcriptomics allows for the measurement of RNA abundance at a high spatial resolution, making it possible to systematically link the morphology of cellular neighbourhoods and spatially localized gene expression. Here, we report the development of a deep learning algorithm for the prediction of local gene expression from haematoxylin-and-eosin-stained histopathology images using a new dataset of 30,612 spatially resolved gene expression data matched to histopathology images from 23 patients with breast cancer. We identified over 100 genes, including known breast cancer biomarkers of intratumoral heterogeneity and the co-localization of tumour growth and immune activation, the expression of which can be predicted from the histopathology images at a resolution of 100 µm. We also show that the algorithm generalizes well to The Cancer Genome Atlas and to other breast cancer gene expression datasets without the need for re-training. Predicting the spatially resolved transcriptome of a tissue directly from tissue images may enable image-based screening for molecular biomarkers with spatial variation.

Authors

  • Bryan He
    Department of Computer Science, Stanford University, Stanford, California.
  • Ludvig Bergenstråhle
    School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Linnea Stenbeck
    School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Abubakar Abid
    Hugging Face, New York, NY, USA.
  • Alma Andersson
    School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Åke Borg
    Division of Oncology and Pathology, Lund University, Lund, Sweden.
  • Jonas Maaskola
    School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden. jonas.maaskola@scilifelab.se.
  • Joakim Lundeberg
    School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden. joakim.lundeberg@scilifelab.se.
  • James Zou
    Department of Biomedical Data Science, Stanford University, Stanford, California.