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CLEM-Reg: an automated point cloud-based registration algorithm for volume correlative light and electron microscopy.

Daniel Krentzel1,2, Matouš Elphick3,4,5,6, Marie-Charlotte Domart3

  • 1Imaging and Modeling Unit, Institut Pasteur, Université Paris Cité, Paris, France. daniel.krentzel@pasteur.fr.

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|September 10, 2025
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Summary
This summary is machine-generated.

This study introduces CLEM-Reg, an automated algorithm for aligning volume correlative light and electron microscopy (vCLEM) datasets. This method significantly speeds up vCLEM analysis and improves protein localization accuracy.

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Area of Science:

  • Cell Biology
  • Microscopy Techniques
  • Bioinformatics

Background:

  • Volume correlative light and electron microscopy (vCLEM) combines fluorescence and ultrastructural imaging.
  • Current vCLEM alignment methods are manual, time-consuming, and subjective.
  • Accurate alignment is crucial for correlating fluorescent signals with cellular structures.

Purpose of the Study:

  • To develop an automated algorithm for 3D alignment of vCLEM datasets.
  • To reduce the time and subjectivity associated with vCLEM data processing.
  • To enable precise localization of fluorescently labeled proteins within ultrastructural context.

Main Methods:

  • Development of CLEM-Reg, an algorithm using probabilistic point cloud registration.
  • Derivation of point clouds from segmentations of common structures in light and electron microscopy data.
  • Application of state-of-the-art open-source segmentation methods.

Main Results:

  • CLEM-Reg automates vCLEM dataset alignment in minutes, drastically reducing processing time.
  • Achieved submicron accuracy in correlating fluorescent signals to target structures in electron microscopy.
  • Successfully identified TGN46-positive transport carriers involved in protein trafficking.

Conclusions:

  • CLEM-Reg offers a robust and efficient solution for vCLEM data alignment.
  • Automated alignment enhances the accuracy and throughput of vCLEM studies.
  • The algorithm facilitates the study of protein trafficking and cellular organization.