Joint micrograph denoising and protein localization in cryo-electron microscopy Cryo-electron microscopy (cryo-EM) is an imaging technique that allows the visualization of proteins and macromolecular complexes at near-atomic resolution. The low electron doses used to prevent radiation damage to the biological samples result in images where the power of noise is 100 times stronger than that of the signal. Accurate…
nextPYP: a comprehensive and scalable platform for characterizing protein variability in situ using single-particle cryo-ET Single-particle cryo-electron tomography (SP-CET) is an emerging technique capable of determining the structure of proteins imaged within the native context of cells at molecular resolution. While high-throughput techniques for sample preparation and tilt-series acquisition are beginning to provide sufficient data to allow structural studies…
Multiple-image super-resolution of cryo-electron micrographs based on deep internal learning Single-particle cryo-electron microscopy (cryo-EM) is a powerful imaging modality capable of visualizing proteins and macromolecular complexes at near-atomic resolution. The low electron-doses used to prevent radiation damage to the biological samples, however, result in images where the power of the noise is 100 times greater than the power of…
Accurate Detection of Proteins in Cryo-Electron Tomograms from Sparse Labels Cryo-electron tomography (CET) combined with sub-volume averaging (SVA), is currently the only imaging technique capable of de-termining the structure of proteins imaged inside cells at molecular reso-lution. To obtain high-resolution reconstructions, sub-volumes containing randomly distributed copies of the protein of interest need be identified, extracted and subjected to SVA,…
High-resolution structure determination using high-throughput electron cryo-tomography The low throughput characteristic of tomographic data acquisition combined with the complex data-analysis pipeline that is required to obtain high-resolution maps, has limited the applicability of this technique to favorable samples or to resolutions that are too low to provide useful mechanistic information. Recently, beam image-shift electron cryo-tomography (BISECT), a strategy to…
Data-driven determination of number of discrete conformations in single-particle cryo-EM Single-particle cryo-EM can be used to image heterogeneous samples containing multiple molecular species, different oligomeric states or distinct conformations. This, however, requires expert-user knowledge and trial-and-error experimentation to determine the correct number of conformations present in a mixture. Here, we propose an approach to address the problem of automatically…
Automated systematic evaluation of cryo-EM specimens with SmartScope We present SmartScope, the first framework to streamline, standardize, and automate specimen evaluation in cryo-electron microscopy. SmartScope employs deep-learning-based object detection to identify and classify features suitable for imaging, allowing it to perform thorough specimen screening in a fully automated manner. A web interface provides remote control over the automated operation…
Cryo-ZSSR: multiple-image super-resolution based on deep internal learning We present a multiple-image super-resolution (SR) algorithm based on deep internal learning designed specifically to work under low-SNR conditions typical of cryo-EM data. Our approach leverages the internal image statistics of cryo-EM movies and does not require training on ground-truth data. When applied to a single-particle dataset of apoferritin, we show…