REliable PIcking by Consensus (REPIC): a consensus methodology for harnessing multiple cryo-EM particle pickers

Abstract Cryo-EM particle identification from micrographs (“picking”) is challenging due to the low signal-to-noise ratio and lack of ground truth for particle locations. State-of-the-art computational algorithms (“pickers”) identify different particle sets, complicating the selection of the best-su...

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Main Authors: Christopher J. F. Cameron, Sebastian J. H. Seager, Fred J. Sigworth, Hemant D. Tagare, Mark B. Gerstein
Format: Article
Language:English
Published: Nature Portfolio 2024-10-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-024-07045-0
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author Christopher J. F. Cameron
Sebastian J. H. Seager
Fred J. Sigworth
Hemant D. Tagare
Mark B. Gerstein
author_facet Christopher J. F. Cameron
Sebastian J. H. Seager
Fred J. Sigworth
Hemant D. Tagare
Mark B. Gerstein
author_sort Christopher J. F. Cameron
collection DOAJ
description Abstract Cryo-EM particle identification from micrographs (“picking”) is challenging due to the low signal-to-noise ratio and lack of ground truth for particle locations. State-of-the-art computational algorithms (“pickers”) identify different particle sets, complicating the selection of the best-suited picker for a protein of interest. Here, we present REliable PIcking by Consensus (REPIC), a computational approach to identifying particles common to the output of multiple pickers. We frame consensus particle picking as a graph problem, which REPIC solves using integer linear programming. REPIC picks high-quality particles even when the best picker is not known a priori or a protein is difficult-to-pick (e.g., NOMPC ion channel). Reconstructions using consensus particles without particle filtering achieve resolutions comparable to those from particles picked by experts. Our results show that REPIC requires minimal (often no) manual intervention, and considerably reduces the burden on cryo-EM users for picker selection and particle picking. Availability: https://github.com/ccameron/REPIC .
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spelling doaj-art-fe00cb92b6fb48f3bf722ecef3f5348e2025-08-20T02:18:35ZengNature PortfolioCommunications Biology2399-36422024-10-017111210.1038/s42003-024-07045-0REliable PIcking by Consensus (REPIC): a consensus methodology for harnessing multiple cryo-EM particle pickersChristopher J. F. Cameron0Sebastian J. H. Seager1Fred J. Sigworth2Hemant D. Tagare3Mark B. Gerstein4Department of Molecular Biophysics and Biochemistry, Yale UniversityDepartment of Molecular Biophysics and Biochemistry, Yale UniversityDepartment of Molecular Biophysics and Biochemistry, Yale UniversityDepartment of Radiology and Biomedical Imaging, Yale UniversityDepartment of Molecular Biophysics and Biochemistry, Yale UniversityAbstract Cryo-EM particle identification from micrographs (“picking”) is challenging due to the low signal-to-noise ratio and lack of ground truth for particle locations. State-of-the-art computational algorithms (“pickers”) identify different particle sets, complicating the selection of the best-suited picker for a protein of interest. Here, we present REliable PIcking by Consensus (REPIC), a computational approach to identifying particles common to the output of multiple pickers. We frame consensus particle picking as a graph problem, which REPIC solves using integer linear programming. REPIC picks high-quality particles even when the best picker is not known a priori or a protein is difficult-to-pick (e.g., NOMPC ion channel). Reconstructions using consensus particles without particle filtering achieve resolutions comparable to those from particles picked by experts. Our results show that REPIC requires minimal (often no) manual intervention, and considerably reduces the burden on cryo-EM users for picker selection and particle picking. Availability: https://github.com/ccameron/REPIC .https://doi.org/10.1038/s42003-024-07045-0
spellingShingle Christopher J. F. Cameron
Sebastian J. H. Seager
Fred J. Sigworth
Hemant D. Tagare
Mark B. Gerstein
REliable PIcking by Consensus (REPIC): a consensus methodology for harnessing multiple cryo-EM particle pickers
Communications Biology
title REliable PIcking by Consensus (REPIC): a consensus methodology for harnessing multiple cryo-EM particle pickers
title_full REliable PIcking by Consensus (REPIC): a consensus methodology for harnessing multiple cryo-EM particle pickers
title_fullStr REliable PIcking by Consensus (REPIC): a consensus methodology for harnessing multiple cryo-EM particle pickers
title_full_unstemmed REliable PIcking by Consensus (REPIC): a consensus methodology for harnessing multiple cryo-EM particle pickers
title_short REliable PIcking by Consensus (REPIC): a consensus methodology for harnessing multiple cryo-EM particle pickers
title_sort reliable picking by consensus repic a consensus methodology for harnessing multiple cryo em particle pickers
url https://doi.org/10.1038/s42003-024-07045-0
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