CryoVesNet: A Dedicated Framework for Synaptic Vesicle Segmentation in Cryo Electron Tomograms

Khosrozadeh, A.; Seeger, R.; Witz, G.; Radecke, J.; Sorensen, J. B.; Zuber, B.

doi:10.1101/2024.02.26.582080

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bioRxiv · 10.1101/2024.02.26.582080

CryoVesNet: A Dedicated Framework for Synaptic Vesicle Segmentation in Cryo Electron Tomograms

Khosrozadeh, A.·Seeger, R.·Witz, G.·Radecke, J.·Sorensen, J. B.·Zuber, B.

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Abstract

Cryo-electron Tomography (Cryo-ET) has the potential to reveal cell structure down to atomic resolution. Nevertheless, cellular cryo-ET data is often highly complex, and visualization, as well as quantification, of subcellular structures require image segmentation. Due to a relatively high level of noise and anisotropic resolution in cryo-ET data, automatic segmentation based on classical computer vision approaches usually does not perform satisfactorily. For this reason, cryo-ET researchers have mostly performed manual segmentation. Communication between neurons relies on neurotransmitter-filled synaptic vesicle (SV) exocytosis. Recruitment of SVs to the plasma membrane is an important means of regulating exocytosis and is influenced by interactions between SVs. Cryo-ET study of the spatial organization of SVs and of their interconnections allows a better understanding of the mechanisms of exocytosis regulation. Extremely accurate SV segmentation is a prerequisite to obtaining a faithful representation of SVs state of connectivity. Hundreds to thousands of SVs are present in a typical synapse, and their time-consuming manual segmentation is a bottleneck in this analysis. Several attempts to automate vesicle segmentation by classical computer vision or machine learning algorithms have not yielded robust results. We addressed this problem by designing a workflow consisting of a U-Net convolutional segmentation network followed by post-processing steps. This combination yields highly accurate results. Furthermore, we provide an interactive tool for accurately segmenting spherical vesicles in a fraction of the time required by available manual segmentation methods. This tool can be used to segment vesicles that were missed by the fully automatic procedure or to quickly segment a handful of vesicles while bypassing the fully automatic procedure. Our pipeline can in principle be used to segment any spherical vesicle in any cell type as well as extracellular vesicles.

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Khosrozadeh, A., Seeger, R., Witz, G., Radecke, J., Sorensen, J. B., Zuber, B.. 2024-02-28. CryoVesNet: A Dedicated Framework for Synaptic Vesicle Segmentation in Cryo Electron Tomograms. https://doi.org/10.1101/2024.02.26.582080

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