Deep learning is widely applicable to phenotyping embryonic development and disease.

Journal: Development (Cambridge, England)
PMID:

Abstract

Genome editing simplifies the generation of new animal models for congenital disorders. However, the detailed and unbiased phenotypic assessment of altered embryonic development remains a challenge. Here, we explore how deep learning (U-Net) can automate segmentation tasks in various imaging modalities, and we quantify phenotypes of altered renal, neural and craniofacial development in Xenopus embryos in comparison with normal variability. We demonstrate the utility of this approach in embryos with polycystic kidneys (pkd1 and pkd2) and craniofacial dysmorphia (six1). We highlight how in toto light-sheet microscopy facilitates accurate reconstruction of brain and craniofacial structures within X. tropicalis embryos upon dyrk1a and six1 loss of function or treatment with retinoic acid inhibitors. These tools increase the sensitivity and throughput of evaluating developmental malformations caused by chemical or genetic disruption. Furthermore, we provide a library of pre-trained networks and detailed instructions for applying deep learning to the reader's own datasets. We demonstrate the versatility, precision and scalability of deep neural network phenotyping on embryonic disease models. By combining light-sheet microscopy and deep learning, we provide a framework for higher-throughput characterization of embryonic model organisms. This article has an associated 'The people behind the papers' interview.

Authors

  • Thomas Naert
    Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland.
  • Özgün Çiçek
    Department of Computer Science, Albert-Ludwigs-University, Freiburg, Germany.
  • Paulina Ogar
    Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland.
  • Max Bürgi
    Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland.
  • Nikko-Ideen Shaidani
    National Xenopus Resource and Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, MA 02543, USA.
  • Michael M Kaminski
    Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin 10115, Germany.
  • Yuxiao Xu
    Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA.
  • Kelli Grand
    Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland.
  • Marko Vujanovic
    Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland.
  • Daniel Prata
    Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland.
  • Friedhelm Hildebrandt
    Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115,USA.
  • Thomas Brox
  • Olaf Ronneberger
    DeepMind, London, EC4A 3TW, UK.
  • Fabian F Voigt
    Laboratory of Neural Circuit Dynamics, Brain Research Institute, University of Zurich, Zurich 8057, Switzerland; Neuroscience Center Zurich, Zurich 8057, Switzerland.
  • Fritjof Helmchen
    Brain Research Institute, University of Zürich, Zurich, Switzerland. helmchen@hifo.uzh.ch.
  • Johannes Loffing
    Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland.
  • Marko E Horb
    National Xenopus Resource and Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, MA 02543, USA.
  • Helen Rankin Willsey
    Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA.
  • Soeren S Lienkamp
    Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland.