De Novo Structural Pattern Mining in Cellular Electron Cryotomograms

Electron cryotomography enables 3D visualization of cells in a near-native state at molecular resolution. The produced cellular tomograms contain detailed information about a plethora of macromolecular complexes, their structures, abundances, and specific spatial locations in the cell. However, extracting this information in a systematic way is very challenging, and current methods usually rely on individual templates of known structures. Here, we propose a framework called “Multi-Pattern Pursuit” for de novo discovery of different complexes from highly heterogeneous sets of particles extracted from entire cellular tomograms without using information of known structures. These initially detected structures can then serve as input for more targeted refinement efforts. Our tests on simulated and experimental tomograms show that our automated method is a promising tool for supporting large-scale template-free visual proteomics analysis.