Abstract
Fourier shell correlation (FSC) has become a standard quantity for resolution estimation in electron cryo-microscopy. However, the resolution determination step is still subjective and not fully automated as it involves a series of map interventions before FSC computation and includes the selection of a common threshold. Here, we apply the statistical methods of permutation sampling and false discovery rate (FDR) control to the resolution-dependent correlation measure. The approach allows fully automated and mask-free resolution determination based on adaptive thresholding of FSC curves. We demonstrate the applicability for global, local and directional resolution estimation and show that the developed criterion termed FDR-FSC gives realistic resolution estimates based on a statistical significance criterion while eliminating the need of any map manipulations. The algorithms are implemented in a user-friendly GUI based software tool termed SPoC (https://github.com/MaximilianBeckers/SPOC).
Footnotes
Highlights We introduce a robust cryo-EM map resolution estimation tool that adaptively thresholds the Fourier Shell correlation curve by statistical methods of false discovery rate control. The procedure accepts untreated half-maps and does not require any masking. We compare the results with reported resolution values determined by common fixed threshold routines. We further demonstrate the utility of the approach by applying it to demanding cases of estimating local and directional resolution.
