Summary
Reliable Picking by Consensus (REPIC) is an ensemble learning approach to cryogenic-electron microscopy (cryo-EM) particle picking. It identifies particles common to multiple picked particle sets (i.e., consensus particles) using graph theory and integer linear programming (ILP). Picked particle sets may be found by a human specialist (manual), template matching, mathematical function (e.g., RELION’s Laplacian-of-Gaussian auto-picking), or machine-learning method. A schematic representation of REPIC applied to the output of three CNN-based particle pickers is below:
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
Citing this work
If REPIC was used in your analysis/study, please cite:
Cameron, C.J.F., Seager, S.J.H., Sigworth, F.J. et al. REliable PIcking by Consensus (REPIC): a consensus methodology for harnessing multiple cryo-EM particle pickers. Commun Biol 7, 1421 (2024). https://doi.org/10.1038/s42003-024-07045-0
Or, include the following BibTeX entry:
@article {Cameron2024,
title = {{REliable} {PIcking} by {Consensus} ({REPIC}): a consensus
methodology for harnessing multiple cryo-{EM} particle pickers},
author = {Cameron, Christopher J F and Seager, Sebastian J H and
Sigworth, Fred J and Tagare, Hemant D and Gerstein, Mark B},
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 .},
journal = {Communications Biology},
publisher = {Nature Publishing Group},
volume = {7},
number = {1},
pages = {1--12},
year = {2024},
doi = {10.1038/s42003-024-07045-0},
language = {en}
}