Evidence map›Paper›PMID 26049077›Full record

ArticleJournal of structural biology2015

Directly reconstructing principal components of heterogeneous particles from cryo-EM images.

Hemant D Tagare, Alp Kucukelbir, Fred J Sigworth, Hongwei Wang, Murali Rao

Abstract read
In one paragraph

Article in Journal of structural biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing 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

41 citing papers in PubMed.

  1. Article
  2. Cryo-EM heterogeneity analysis using regularized covariance estimation and kernel regression.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
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  5. Article
  6. Article
  7. Review
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  11. Review
  12. Amortized Inference for Heterogeneous Reconstruction in Cryo-EM.Advances in neural information processing systems · 2022
    Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Hemant D TagareDept. of Diagnostic Radiology, Yale University, CT 06520, United States; Dept. of Biomedical Engineering, Yale University, CT 06520, United States. Electronic address: hemant.tagare@yale.edu.
Alp KucukelbirData Science Institute, Columbia University, NY 10027, United States; Dept. of Computer Science, Columbia University, NY 10027, United States.
Fred J SigworthDept. of Cellular and Molecular Physiology, Yale University, CT 06520, United States; Dept. of Biomedical Engineering, Yale University, CT 06520, United States.
Hongwei WangCenter for Struct. Biol., School of Life Sciences, Tsinghua University, Beijing 100084, China.
Murali RaoDept. of Mathematics, University of Florida, FL 32611-8105, United States.

Funding

FLUCTUATIONS IN IONIC CURRENT THROUGH MEMBRANE CHANNELSR01NS021501 · NINDS · YALE UNIVERSITY · PI SIGWORTH, FREDERICK J · 1985 to 2024
$10.9M
Cryo-EM 3D Reconstruction of Flexible ParticlesR01GM095658 · NIGMS · YALE UNIVERSITY · PI TAGARE, HEMANT D · 2011 to 2014
$1.1M
NIGMS NIH HHS 1R01GM095658NIGMS NIH HHS R01 GM095658NINDS NIH HHS R01 NS021501
6 · The paper itself

Abstract

Structural heterogeneity of particles can be investigated by their three-dimensional principal components. This paper addresses the question of whether, and with what algorithm, the three-dimensional principal components can be directly recovered from cryo-EM images. The first part of the paper extends the Fourier slice theorem to covariance functions showing that the three-dimensional covariance, and hence the principal components, of a heterogeneous particle can indeed be recovered from two-dimensional cryo-EM images. The second part of the paper proposes a practical algorithm for reconstructing the principal components directly from cryo-EM images without the intermediate step of calculating covariances. This algorithm is based on maximizing the posterior likelihood using the Expectation-Maximization algorithm. The last part of the paper applies this algorithm to simulated data and to two real cryo-EM data sets: a data set of the 70S ribosome with and without Elongation Factor-G (EF-G), and a data set of the influenza virus RNA dependent RNA Polymerase (RdRP). The first principal component of the 70S ribosome data set reveals the expected conformational changes of the ribosome as the EF-G binds and unbinds. The first principal component of the RdRP data set reveals a conformational change in the two dimers of the RdRP.

Indexed as

AlgorithmsComputer SimulationCryoelectron MicroscopyInfluenza A virusLikelihood FunctionsModels, MolecularPrincipal Component AnalysisProtein FoldingProtein Structure, TertiaryRibosomesRNA-Dependent RNA PolymeraseRNA-Dependent RNA PolymeraseEM algorithmHeterogeneityMaximum-likelihoodPrincipal componentsSingle particle reconstruction

Identifiers

PMID26049077
PMCPMC4536832

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Registered trials

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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.