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Lamm, L. ; Righetto, R.D. ; Wietrzynski, W. ; Pöge, M.* ; Martinez-Sanchez, A.* ; Peng, T. ; Engel, B.D.

MemBrain: A deep learning-aided pipeline for detection of membrane proteins in Cryo-electron tomograms.

Comput. Meth. Programs Biomed. 224:106990 (2022)
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BACKGROUND AND OBJECTIVE: Cryo-electron tomography (cryo-ET) is an imaging technique that enables 3D visualization of the native cellular environment at sub-nanometer resolution, providing unpreceded insights into the molecular organization of cells. However, cryo-electron tomograms suffer from low signal-to-noise ratios and anisotropic resolution, which makes subsequent image analysis challenging. In particular, the efficient detection of membrane-embedded proteins is a problem still lacking satisfactory solutions. METHODS: We present MemBrain - a new deep learning-aided pipeline that automatically detects membrane-bound protein complexes in cryo-electron tomograms. After subvolumes are sampled along a segmented membrane, each subvolume is assigned a score using a convolutional neural network (CNN), and protein positions are extracted by a clustering algorithm. Incorporating rotational subvolume normalization and using a tiny receptive field simplify the task of protein detection and thus facilitate the network training. RESULTS: MemBrain requires only a small quantity of training labels and achieves excellent performance with only a single annotated membrane (F1 score: 0.88). A detailed evaluation shows that our fully trained pipeline outperforms existing classical computer vision-based and CNN-based approaches by a large margin (F1 score: 0.92 vs. max. 0.63). Furthermore, in addition to protein center positions, MemBrain can determine protein orientations, which has not been implemented by any existing CNN-based method to date. We also show that a pre-trained MemBrain program generalizes to tomograms acquired using different cryo-ET methods and depicting different types of cells. CONCLUSIONS: MemBrain is a powerful and annotation-efficient tool for the detection of membrane protein complexes in cryo-ET data, with the potential to be used in a wide range of biological studies. It is generalizable to various kinds of tomograms, making it possible to use pretrained models for different tasks. Its efficiency in terms of required annotations also allows rapid training and fine-tuning of models. The corresponding code, pretrained models, and instructions for operating the MemBrain program can be found at: https://github.com/CellArchLab/MemBrain.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cryo-electron Tomography ; Annotation-efficient ; Deep Learning ; Membrane Protein ; Particle Picking ; Protein Localization
Language english
Publication Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 0169-2607
e-ISSN 1872-7565
Quellenangaben Volume: 224, Issue: , Pages: , Article Number: 106990 Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)
Helmholtz Artifical Intelligence Cooperation Unit (HAICU)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30205 - Bioengineering and Digital Health
Research field(s) Pioneer Campus
Enabling and Novel Technologies
PSP Element(s) G-510008-001
G-530006-001
Scopus ID 85134568571
PubMed ID 35858496
Erfassungsdatum 2022-11-03