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Integrating spatial gene expression and breast tumour morphology via deep learning

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From Nature Biomedical Engineering

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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.

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Fig. 1: ST-Net pipeline and data.
Fig. 2: Results from the ST-Net predictions.
Fig. 3: Three example patches and regions of interest identified by interpreting ST-Net.
Fig. 4: UMAP visualization of the ST-Net latent space.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. Raw files for the breast cancer samples are available through a Materials transfer agreement with Å.B. (ake.borg@med.lu.se). All images and processed data are available at http://www.spatialtranscriptomicsresearch.org. The 10x Spatial Genomics data can be downloaded from https://wp.10xgenomics.com/spatial-transcriptomics. All data from TGCA are publicly available from the Genomic Data Commons Data Portal (https://portal.gdc.cancer.gov).

Code availability

The code for ST-Net is available at https://github.com/bryanhe/ST-Net.

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Acknowledgements

J.Z. is supported by the NSF (grant no. CCF 1763191), NIH (grant nos. R21 MD012867-01, P30AG059307 and U01MH098953) and grants from the Silicon Valley Foundation and Chan–Zuckerberg Initiative. J.L. is supported by the Swedish Foundation for Strategic Research, Swedish Cancer Society and Swedish Research Council.

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Authors and Affiliations

  1. Department of Computer Science, Stanford University, Stanford, CA, USA

    Bryan He & James Zou

  2. School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden

    Ludvig Bergenstråhle, Linnea Stenbeck, Alma Andersson, Jonas Maaskola & Joakim Lundeberg

  3. Department of Electrical Engineering, Stanford University, Stanford, CA, USA

    Abubakar Abid & James Zou

  4. Division of Oncology and Pathology, Lund University, Lund, Sweden

    Åke Borg

  5. Department of Biomedical Data Science, Stanford University, Stanford, CA, USA

    James Zou

  6. Chan–Zuckerberg Biohub, San Francisco, CA, USA

    James Zou

Authors
  1. Bryan He
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Contributions

All of the authors contributed to the project planning and writing of the manuscript. B.H. and L.B. performed analysis. L.S., Å.B. and J.L. generated data. J.M., J.L. and J.Z. supervised the project.

Corresponding authors

Correspondence to Jonas Maaskola, Joakim Lundeberg or James Zou.

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Competing interests

J.L. is an author on patent nos. PCT/EP2012/056823 (WO2012/140224), PCT/EP2013/071645 (WO2014/060483) and PCT/EP2016/057355 applied for by Spatial Transcriptomics AB/10x Genomics Inc. covering the described technology.

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He, B., Bergenstråhle, L., Stenbeck, L. et al. Integrating spatial gene expression and breast tumour morphology via deep learning. Nat Biomed Eng 4, 827–834 (2020). https://doi.org/10.1038/s41551-020-0578-x

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  • DOI: https://doi.org/10.1038/s41551-020-0578-x

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