Evidence map›Paper›PMID 40263313›Full record

ArticleNature communications2025

Real-space heterogeneous reconstruction, refinement, and disentanglement of CryoEM conformational states with HetSIREN.

David Herreros, Carlos Perez Mata, Chari Noddings, Deli Irene, James Krieger, David A Agard, Ming-Daw Tsai, Carlos Oscar Sanchez Sorzano, Jose Maria Carazo

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

12 citing papers in PubMed.

  1. CryoJAX: a cryo-electron microscopy image-simulation library in JAX.Acta crystallographica. Section D, Structural biology · 2026
    Article
  2. Review
  3. The Open Conformation of CCT: How to Achieve High Resolution Using CryoEM.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  4. Article
  5. Article
  6. cryoJAX: A Cryo-electron Microscopy Image Simulation Library In JAX.bioRxiv : the preprint server for biology · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. InstaMap: instant-NGP for cryo-EM density maps.Acta crystallographica. Section D, Structural biology · 2025
    Article
  12. Automated model-free analysis of cryo-EM volume ensembles with SIREn.bioRxiv : the preprint server for biology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

David HerrerosCentro Nacional de Biotecnologia-CSIC, C/ Darwin, 3, Cantoblanco, Madrid, Spain. dherreros@cnb.csic.es.ORCID http://orcid.org/0000-0003-1509-1649
Carlos Perez MataCentro Nacional de Biotecnologia-CSIC, C/ Darwin, 3, Cantoblanco, Madrid, Spain.ORCID http://orcid.org/0000-0003-3381-7431
Chari NoddingsAltos Labs, Redwood City, CA, USA.
Deli IreneInstitute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
James KriegerCentro Nacional de Biotecnologia-CSIC, C/ Darwin, 3, Cantoblanco, Madrid, Spain.ORCID http://orcid.org/0000-0001-6194-6244
David A AgardDepartment of Biochemistry & Biophysics, University of California, San Francisco, CA, USA.
Ming-Daw TsaiInstitute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.ORCID http://orcid.org/0000-0003-1374-0414
Carlos Oscar Sanchez SorzanoCentro Nacional de Biotecnologia-CSIC, C/ Darwin, 3, Cantoblanco, Madrid, Spain.ORCID http://orcid.org/0000-0002-9473-283X
Jose Maria CarazoCentro Nacional de Biotecnologia-CSIC, C/ Darwin, 3, Cantoblanco, Madrid, Spain.ORCID http://orcid.org/0000-0003-0788-8447

Funding

Glacios™ Cryo Transmission Electron Microscope with 200 kV XFEG opticsS10OD026881 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2019 to 2019
$1.8M
EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) HighResCells (ERC - 2018 - SyG, Proposal: 810057)NIH HHS S10 OD026881
6 · The paper itself

Abstract

Single-particle analysis by Cryo-electron microscopy (CryoEM) provides direct access to the conformations of macromolecules. Traditional methods assume discrete conformations, while newer algorithms estimate conformational landscapes representing the different structural states a biomolecule explores. This work presents HetSIREN, a deep learning-based method that can fully reconstruct or refine a CryoEM volume in real space based on the structural information summarized in a conformational latent space. HetSIREN is defined as an accurate space-based method that allows spatially focused analysis and the introduction of sinusoidal hypernetworks with proven high analytics capacities. Continuing with innovations, HetSIREN can also refine the images' pose while conditioning the network with additional constraints to yield cleaner high-quality volumes, as well as addressing one of the most confusing issues in heterogeneity analysis, as it is the fact that structural heterogeneity estimations are entangled with pose estimation (and to a lesser extent with CTF estimation) thanks to its decoupling architecture.

Identifiers

PMID40263313
PMCPMC12015509

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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.