Central Feature Network Enables Accurate Detection of Both Small and Large Particles in Cryo-Electron Tomography

Advances in cryo-electron tomography (cryo-ET) have enabled the visualization of molecules within their native cellular environments in three-dimensions (3D). These visualizations are essential for studying the functions of biological entities in their natural conditions. Recently, deep learning techniques have shown significant success in tackling the challenge of particle detection in cryo-ET data. However, accurately identifying and classifying multi-class molecules remain challenging due to factors like low signal-to-noise ratios and the wide range of particle sizes. In this study, we introduce a novel framework CFNPicker for 3D object detection applied to cryo-ET analysis. A major advantage of our method is the design of central feature network (CFN) to integrate central features across multiple scales, allowing for the accurate detection of both small ( $⩽$200) and large ( $⩾$600) molecules. Additionally, we propose an adaptive weighted sampling training strategy to distinguish the complex noise distribution in the background, reducing false positive particles. We also construct the localization label to explicitly utilize the size and position variations of multi-class protein structures. Compared with existing methods, CFN improves the F1 score for classification by 3.6%, 7.3%, 6.6%, and 5.1% for the four smallest molecules tested respectively, while preserving similar or higher F1 scores for other molecules analyzed.