Two datasets are better than one: method of double moments for 3D reconstruction in cryo-EM
Year: 2026
Type: article
Abstract: Cryo-electron microscopy is a powerful imaging technique for reconstructing three-dimensional molecular structures from noisy tomographic projection images of randomly oriented particles. We introduce a new data fusion framework, termed the method of double moments, which reconstructs molecular structures from two instances of the second-order moment of projection images obtained under distinct orientation distributions: one uniform, the other non-uniform and unknown. We prove that these moments generically uniquely determine the underlying structure, up to a global rotation and reflection, and we develop a convex-relaxation-based algorithm that achieves accurate recovery using only second-order statistics. Our results demonstrate the advantage of collecting and modeling multiple datasets under different experimental conditions, illustrating that leveraging dataset diversity can substantially enhance reconstruction quality in computational imaging tasks.
Source: Inverse Problems
Authors: Joe Kileel, Oscar Mickelin, Amit Singer, Sheng Xu
Language: English
Subfield: Structural Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,325
Funders: National Science Foundation, Alfred P. Sloan Foundation, Simons Foundation, National Institutes of Health, Directorate for Computer and Information Science and Engineering, National Institute of General Medical Sciences, Division of Mathematical Sciences, Division of Information and Intelligent Systems, Advanced Scientific Computing Research, Air Force Office of Scientific Research
Awards: G1523888516, NSF-BSF: Theory, algorithms, and applications of estimation over groups, Reconstruction of heterogeneous and small macromolecules by cyro-EM, Collaborative Research: RI: Medium: Bridging the Semantic-Metric Gap via Multinocular Image Integration, G4688056592, NSF-BSF: Computational Methods for Shape Space Analysis in Structural Biology, G6407678319, G7850582900, G8535008652, FDT-BioTech: A digital twin framework for developing and analyzing virtual patient cohorts to enable virtual clinical trials, G915999455
OpenAlex ID: W4416188333
