The field of cryo-electron microscopy (cryo-EM) has become a leading method for solving high-resolution structures of biomolecules in solution. The method of transmission electron microscopy used to obtain these structures involves imaging molecules in a thin layer of amorphous vitreous ice by shooting electrons at them and recording excitation events on the other side. The 3D molecule can then be reconstructed from the resulting 2D images (usually hundreds of thousands to millions of them) once the angle of the molecules during imaging can be estimated. While this method of obtaining 3D structures of biomolecules was first developed in the 1970s and 1980s, in approximately 2014 hardware and software developments resulted in the “Resolution Revolution” in cryo-EM, thus leading to the method now being competitive with X-ray crystallography for the determination of high-resolution molecular structures. One of the key advantages of the method over crystallography however is that crystals are no longer a requirement for high-resolution structure determination, providing potential access to the conformational heterogeneity of these molecules — an area where methods development is still underway.
June 2023: Cryo-EM Heterogeneity Challenge
Here we have provided two single-particle datasets with continuous heterogeneity, providing the opportunity to compare results of various heterogeneity analysis methods on identical datasets. Please use your method of choice to analyze these data and provide results in the form of 80 volumes (at 2.146 Å/voxel aligned to the reference volume) with the relative population of each, and their coordinates along the dominant degree of freedom (finely sampling the direction of greatest conformational change). We are providing angles with the datasets, but note that they are only provided as a starting point for the analysis. We expect better results can be obtained with further refinement.
The initially released datasets had 33 742 particles each, they were designed to be small and robust for rapid methods development. Upon feedback from the community, there was also considerable interest in studying a dataset with many more particles. Hence, we have produced a dataset with the same characteristics as the second dataset but many more images (674840).
This expanded dataset can be downloaded using Globus at the following link (541 GB).
The 2023 challenge has now closed and submissions are being analyzed. However, if you are interested in a late submission, feel free to still submit via this form, but you are not guaranteed to be included in the analysis.
Link to dataset 1: (25.2 GB)
Link to dataset 2: (37.8 GB)