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Orientation-invariant autoencoders learn robust representations for shape profiling of cells and organelles

Author

Listed:
  • James Burgess

    (Stanford University)

  • Jeffrey J. Nirschl

    (Stanford University)

  • Maria-Clara Zanellati

    (University of North Carolina at Chapel Hill)

  • Alejandro Lozano

    (Stanford University)

  • Sarah Cohen

    (University of North Carolina at Chapel Hill)

  • Serena Yeung-Levy

    (Stanford University
    Chan Zuckerberg Biohub - San Francisco
    Stanford University)

Abstract

Cell and organelle shape are driven by diverse genetic and environmental factors and thus accurate quantification of cellular morphology is essential to experimental cell biology. Autoencoders are a popular tool for unsupervised biological image analysis because they learn a low-dimensional representation that maps images to feature vectors to generate a semantically meaningful embedding space of morphological variation. The learned feature vectors can also be used for clustering, dimensionality reduction, outlier detection, and supervised learning problems. Shape properties do not change with orientation, and thus we argue that representation learning methods should encode this orientation invariance. We show that conventional autoencoders are sensitive to orientation, which can lead to suboptimal performance on downstream tasks. To address this, we develop O2-variational autoencoder (O2-VAE), an unsupervised method that learns robust, orientation-invariant representations. We use O2-VAE to discover morphology subgroups in segmented cells and mitochondria, detect outlier cells, and rapidly characterise cellular shape and texture in large datasets, including in a newly generated synthetic benchmark.

Suggested Citation

  • James Burgess & Jeffrey J. Nirschl & Maria-Clara Zanellati & Alejandro Lozano & Sarah Cohen & Serena Yeung-Levy, 2024. "Orientation-invariant autoencoders learn robust representations for shape profiling of cells and organelles," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45362-4
    DOI: 10.1038/s41467-024-45362-4
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