High-confidence 3D template matching for cryo-electron tomography

Cruz-León, Sergio; Majtner, Tomáš; Hoffmann, Patrick C.; Kreysing, Jan Philipp; Kehl, Sebastian; Tuijtel, Maarten; Schaefer, Stefan L.; Geißler, Katharina; Beck, Martin; Turoňová, Beata; Hummer, Gerhard

doi:10.1038/s41467-024-47839-8

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High-confidence 3D template matching for cryo-electron tomography

MPS-Authors

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Cruz-León, Sergio
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;

/persons/resource/persons293277

Majtner, Tomáš
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;

/persons/resource/persons284135

Hoffmann, Patrick C.
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;

/persons/resource/persons284138

Kreysing, Jan Philipp
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;
IMPRS-CBP, Max Planck Institute of Biophysics, Max Planck Society;

/persons/resource/persons284141

Tuijtel, Maarten
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;

/persons/resource/persons263441

Schaefer, Stefan L.
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;

/persons/resource/persons298343

Geißler, Katharina
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;
IMPRS-CBP, Max Planck Institute of Biophysics, Max Planck Society;

/persons/resource/persons232071

Beck, Martin
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;
Institute of Biochemistry, Goethe University Frankfurt, Frankfurt am Main, Germany;

/persons/resource/persons188929

Turoňová, Beata
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;

/persons/resource/persons15259

Hummer, Gerhard
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;
Institute of Biophysics, Goethe University Frankfurt, Frankfurt am Main, Germany;

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引用

Cruz-León, S., Majtner, T., Hoffmann, P. C., Kreysing, J. P., Kehl, S., Tuijtel, M., Schaefer, S. L., Geißler, K., Beck, M., Turoňová, B., & Hummer, G. (2024). High-confidence 3D template matching for cryo-electron tomography. Nature Communications, 15:. doi:10.1038/s41467-024-47839-8.

引用: https://hdl.handle.net/21.11116/0000-000F-4B02-B

要旨

Visual proteomics attempts to build atlases of the molecular content of cells but the automated annotation of cryo electron tomograms remains challenging. Template matching (TM) and methods based on machine learning detect structural signatures of macromolecules. However, their applicability remains limited in terms of both the abundance and size of the molecular targets. Here we show that the performance of TM is greatly improved by using template-specific search parameter optimization and by including higher-resolution information. We establish a TM pipeline with systematically tuned parameters for the automated, objective and comprehensive identification of structures with confidence 10 to 100-fold above the noise level. We demonstrate high-fidelity and high-confidence localizations of nuclear pore complexes, vaults, ribosomes, proteasomes, fatty acid synthases, lipid membranes and microtubules, and individual subunits inside crowded eukaryotic cells. We provide software tools for the generic implementation of our method that is broadly applicable towards realizing visual proteomics.