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ETSAM: Effectively Segmenting Cell Membranes in cryo-Electron Tomograms

Selvaraj, J.; Cheng, J.

2025-11-26 bioinformatics
10.1101/2025.11.23.689996 bioRxiv
Show abstract

Cryogenic Electron Tomography (cryo-ET) is an emerging experimental technique to visualize cell structures and macromolecules in their native cellular environment. Accurate segmentation of cell structures in cryo-ET tomograms, such as cell membranes, is crucial to advance our understanding of cellular organization and function. However, several inherent limitations in cryo-ET tomograms, including the very low signal-to-noise ratio, missing wedge artifacts from limited tilt angles, and other noise artifacts, collectively hinder the reliable identification and delineation of these structures. In this study, we introduce ETSAM - a two-stage Segment Anything Model 2 (SAM2)-based fine-tuned AI method that effectively segments cell membranes in cryo-ET tomograms. It is trained on a diverse dataset comprising 83 experimental tomograms from the CryoET Data Portal (CDP) database and 28 simulated tomograms generated using PolNet. ETSAM achieves state-of-the-art performance on an independent test set comprising 10 experimental tomograms for which ground-truth annotations are available. It robustly segments cell membranes with high sensitivity and precision, significantly outperforming existing deep learning methods.

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