ArticleNature methods2025
Overcoming the preferred-orientation problem in cryo-EM with self-supervised deep learning.
Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Integrating multitemperature sample preparation with particle rebalancing addresses preferred orientation.PNAS nexus · 2026Article
- Cooperative mechanism of neurotransmitter recognition and transport by the human vesicular polyamine transporter.Nature communications · 2026Article
- Cryo-EM structure of soluble VPS13C suggests its regulation by a conformational switch and by calmodulin.Molecular cell · 2026Article
- Cryo-EM structure of African horse sickness virus VP2 receptor-binding protein enables nanoparticle vaccine design.Nature communications · 2026Article
- UsingbioRxiv : the preprint server for biology · 2026Article
- prismPYP: Power-spectrum and image domain learning for self-supervised micrograph evaluation.Structure (London, England : 1993) · 2026Article
- Bridging structure and function: artificial intelligence-based modelling of kidney proteins.Nature reviews. Nephrology · 2026Review
- EMReady2: improvement of cryo-EM and cryo-ET maps by local quality-aware deep learning with Mamba.Nature communications · 2026Article
- Overcoming the challenge of preferred particle orientation in cryo-EM.Nature reviews. Molecular cell biology · 2026Article
- ICECREAM: high-fidelity equivariant cryo-electron tomography.Acta crystallographica. Section D, Structural biology · 2026Article
- Cryo-EM Structures Reveal the Molecular Basis of Asymmetric Allosteric Activation by MMOB in the Hydroxylase of Soluble Methane Monooxygenase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Subcellular Structures in Native Hippocampal Synapses Revealed by Cryo-electron Tomography.Neuroscience bulletin · 2026Article
- Transcription activation mechanism of a noncanonical DNA damage response pathway by the WYL-activator, DriD.Science advances · 2026Article
- A Surfactant Cocktail Overcomes Air-Water Interface Artifacts in Single-Particle CryoEM.bioRxiv : the preprint server for biology · 2026Article
- Effector conformational plasticity enables lineage-specific secretion via Hcp heterohexamers in gut symbionts.Nature communications · 2026Article
- Mechanism of beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy.Nature communications · 2026Article
- Article
- A comprehensive foundation model for cryo-EM image processing.Nature methods · 2026Article
- Human broadly neutralizing influenza B virus antibodies recognizing hemagglutinin computationally optimized broadly reactive antigens.Frontiers in immunology · 2026Article
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Abstract
While advances in single-particle cryo-EM have enabled the structural determination of macromolecular complexes at atomic resolution, particle orientation bias (the 'preferred' orientation problem) remains a complication for most specimens. Existing solutions have relied on biochemical and physical strategies applied to the specimen and are often complex and challenging. Here, we develop spIsoNet, an end-to-end self-supervised deep learning-based software to address map anisotropy and particle misalignment caused by the preferred-orientation problem. Using preferred-orientation views to recover molecular information in under-sampled views, spIsoNet improves both angular isotropy and particle alignment accuracy during 3D reconstruction. We demonstrate spIsoNet's ability to generate near-isotropic reconstructions from representative biological systems with limited views, including ribosomes, β-galactosidases and a previously intractable hemagglutinin trimer dataset. spIsoNet can also be generalized to improve map isotropy and particle alignment of preferentially oriented molecules in subtomogram averaging. Therefore, without additional specimen-preparation procedures, spIsoNet provides a general computational solution to the preferred-orientation problem.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.