Reliable Picking by Consensus (REPIC)

An ensemble learning approach to cryogenic-electron microscopy (cryo-EM) particle picking. Manuscript is under peer-review, and currently available in preprint.


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:

Schematic representation of REPIC


Cryo-EM (cryogenic electron microscopy) particle identification from micrographs (i.e., picking) is challenging due to the low signal-to-noise ratio and lack of ground truth for particle locations. Moreover, current computational methods (“pickers”) identify different particle sets, complicating the selection of the best-suited picker for a protein of interest. Here, we present REPIC, an ensemble learning methodology that uses multiple pickers to find consensus particles. REPIC identifies consensus particles by framing its task as a graph problem and using integer linear programming to select particles. REPIC picks high-quality particles when the best picker is not known a priori and for known difficult-to-pick particles (e.g., TRPV1). Reconstructions using consensus particles achieve resolutions comparable to those from particles picked by experts, without the need for downstream particle filtering. Overall, our results show REPIC requires minimal (often no) manual picking and significantly reduces the burden on cryo-EM users for picker selection and particle picking.

Citing this work

If REPIC was used in your analysis/study, please cite:

Cameron, C.J.F., Seager, S.J.H., Sigworth, F.J., Tagare, H.D., and Gerstein, M.B. REPIC - an ensemble learning methodology for cryo-EM particle picking. BioRxiv. DOI: 10.1101/2023.05.13.540636

Or, include the following BibTeX entry:

@article {Cameron2023,
	author = {Christopher JF Cameron and Sebastian JH Seager and Fred J Sigworth and Hemant D Tagare and Mark B Gerstein},
	title = {REPIC {\textemdash} an ensemble learning methodology for cryo-EM particle picking},
	elocation-id = {2023.05.13.540636},
	year = {2023},
	doi = {10.1101/2023.05.13.540636},
	publisher = {Cold Spring Harbor Laboratory},
	URL = {},
	eprint = {},
	journal = {bioRxiv}