Evidence map›Paper›PMID 38459385›Full record

ArticleNature methods2024

Learning structural heterogeneity from cryo-electron sub-tomograms with tomoDRGN.

Barrett M Powell, Joseph H Davis

Open access · greenAbstract read
In one paragraph

Article in Nature methods, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
23.0field-weighted citation impact, top 1% of its field
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

42 citing papers in PubMed, 48 citations in OpenAlex.

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  20. In-cell chromatin structure by Cryo-FIB and Cryo-ET.Current opinion in structural biology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Barrett M PowellDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. bmp@mit.edu.ORCID http://orcid.org/0000-0003-4228-2977
Joseph H DavisDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. jhdavis@mit.edu.ORCID http://orcid.org/0000-0002-8858-8907
Massachusetts Institute of Technology · US

Funding

PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
Tools to determine and analyze the structures of molecular machines in motionR01GM144542 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Joseph Davis · 2022 to 2026
$1.6M
National Science Foundation (NSF) 2046778NIGMS NIH HHS R01 GM144542NIGMS NIH HHS T32 GM007287U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 5T32-GM007287U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01-GM144542
6 · The paper itself

Abstract

Cryo-electron tomography (cryo-ET) enables observation of macromolecular complexes in their native, spatially contextualized cellular environment. Cryo-ET processing software to visualize such complexes at nanometer resolution via iterative alignment and averaging are well developed but rely upon assumptions of structural homogeneity among the complexes of interest. Recently developed tools allow for some assessment of structural diversity but have limited capacity to represent highly heterogeneous structures, including those undergoing continuous conformational changes. Here we extend the highly expressive cryoDRGN (Deep Reconstructing Generative Networks) deep learning architecture, originally created for single-particle cryo-electron microscopy analysis, to cryo-ET. Our new tool, tomoDRGN, learns a continuous low-dimensional representation of structural heterogeneity in cryo-ET datasets while also learning to reconstruct heterogeneous structural ensembles supported by the underlying data. Using simulated and experimental data, we describe and benchmark architectural choices within tomoDRGN that are uniquely necessitated and enabled by cryo-ET. We additionally illustrate tomoDRGN's efficacy in analyzing diverse datasets, using it to reveal high-level organization of human immunodeficiency virus (HIV) capsid complexes assembled in virus-like particles and to resolve extensive structural heterogeneity among ribosomes imaged in situ.

Indexed as

Cryoelectron MicroscopyElectron Microscope TomographyImage Processing, Computer-AssistedSoftwareDeep LearningHIV-1Humans

Identifiers

PMID38459385
PMCPMC11655136
OpenAlexW4392596450

What Socratic holds

Textmetadata
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Registered trials

None linked

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 Socratic graph.