Xu, M. et al. Structure https://doi.org/10.1016/j.str.2019.01.005 (2019).
Cryo-electron tomography (cryo-ET) potentially offers a powerful way to map macromolecular complexes in cells frozen in a close-to-native state. Identifying and locating complexes in the crowded environment of a cell is challenging, however. Most current methods use known structures as templates for mapping complexes, but this approach is inherently limited and cannot be applied to unknown structures. Xu et al. report a template-free method that they call “multi-pattern pursuit” and that applies a pattern-generation, selection, and alignment approach to map the locations of complexes in cellular tomograms without using information from known structures. The researchers tested their method using simulated, crowded mixtures of complexes, and also applied it to discover patterns in three different experimental cellular tomograms of whole bacteria. Though still at a proof-of-principle stage, the method shows promise for ‘visual proteomics’ investigations of single cells.