The CAHRA Challenge: A Community-Wide Assessment of Cryo-EM Heterogeneous Reconstruction Algorithms
Year: 2026
Type: preprint
Abstract: The ability of cryo-electron microscopy (cryo-EM) to interrogate the atomic structure and motion of biomolecules has motivated the development of a wide range of algorithms for heterogeneity analysis. However, evaluating and comparing these methods remains challenging because ground-truth structures are generally unknown for experimental samples. Here, we introduce the 2026 Community-Wide Assessment of Heterogeneous Reconstruction Algorithms (CAHRA), a community-wide challenge centered on three benchmark datasets that probe distinct tasks in heterogeneity analysis. These include (1) compositional heterogeneity arising from mixtures of distinct protein complexes, (2) continuous conformational variability and atomic modeling, and (3) entanglement between molecular conformation and image pose. We describe the design, construction, and validation of these datasets, as well as their use in the recently completed CAHRA Challenge.
Language: English
Subfield: Structural Biology
Domain: Life Sciences
Open Access status: green
Awards: G1324744716, G2620866968, Collaborative Computational Project for cryo electron microscopy (CCP-EM): expanding the reach of cryoEM, Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM): 2021 - 2026, Algorithms and Software for Biomolecular Structure Determination at the Proteome Scale, G934645382, HECBioSim: The UK High End Computing Consortium for Biomolecular Simulation.
OpenAlex ID: W7213504137