Evidence map›Paper›PMID 40571741›Full record

ArticleNature methods2025

CryoDRGN-AI: neural ab initio reconstruction of challenging cryo-EM and cryo-ET datasets.

Axel Levy, Rishwanth Raghu, J Ryan Feathers, Michal Grzadkowski, Frédéric Poitevin, Jake D Johnston, Francesca Vallese, Oliver Biggs Clarke, Gordon Wetzstein, Ellen D Zhong

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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 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Axel LevyDepartment of Electrical Engineering, Stanford University, Stanford, CA, USA.
Rishwanth RaghuDepartment of Computer Science, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0009-0006-6651-142X
J Ryan FeathersDepartment of Computer Science, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-4402-4659
Michal GrzadkowskiDepartment of Computer Science, Princeton University, Princeton, NJ, USA.
Frédéric PoitevinSLAC National Accelerator Laboratory, Menlo Park, CA, USA.ORCID http://orcid.org/0000-0002-3181-8652
Jake D JohnstonDepartment of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA.
Francesca ValleseDepartment of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA.
Oliver Biggs ClarkeDepartment of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0003-1876-196X
Gordon WetzsteinDepartment of Electrical Engineering, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9243-6885
Ellen D ZhongDepartment of Computer Science, Princeton University, Princeton, NJ, USA. zhonge@princeton.edu.ORCID http://orcid.org/0000-0001-6345-1907

Funding

U.S. Department of Energy (DOE) DE-AC02-76SF00515U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) 1R01HL168178
6 · The paper itself

Abstract

Proteins and other biomolecules form dynamic macromolecular machines that are tightly orchestrated to move, bind and perform chemistry. Cryo-electron microscopy and cryo-electron tomography can access the intrinsic heterogeneity of these complexes and are therefore key tools for understanding their function. However, three-dimensional reconstruction of the collected imaging data presents a challenging computational problem, especially without any starting information, a setting termed ab initio reconstruction. Here we introduce cryoDRGN-AI, a method leveraging an expressive neural representation and combining an exhaustive search strategy with gradient-based optimization to process challenging heterogeneous datasets. Using cryoDRGN-AI, we reveal new conformational states in large datasets, reconstruct previously unresolved motions from unfiltered datasets and demonstrate ab initio reconstruction of biomolecular complexes from in situ data. With this expressive and scalable model for structure determination, we hope to unlock the full potential of cryo-electron microscopy and cryo-electron tomography as a high-throughput tool for structural biology and discovery.

Indexed as

Cryoelectron MicroscopyElectron Microscope TomographyImage Processing, Computer-AssistedNeural Networks, ComputerAlgorithmsImaging, Three-DimensionalModels, Molecular

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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.