%0 Journal Article
%A Beckers, Maximilian
%A Jakobi, Arjen J.
%A Sachse, Carsten
%T Thresholding of cryo-EM density maps by false discovery rate control
%J IUCrJ
%V 6
%N 1
%@ 2052-2525
%C Chester
%M FZJ-2018-07367
%P 1-16
%D 2019
%X Cryo-EM now commonly generates close-to-atomic resolution as well as intermediate resolution maps from macromolecules observed in isolation and in situ. Interpreting these maps remains a challenging task owing to poor signal in the highest resolution shells and the necessity to select a threshold for density analysis. In order to facilitate this process, a statistical framework for the generation of confidence maps by multiple hypothesis testing and false discovery rate (FDR) control has been developed. In this way, three-dimensional confidence maps contain signal separated from background noise in the form of local detection rates of EM density values. It is demonstrated that confidence maps and FDR-based thresholding can be used for the interpretation of near-atomic resolution single-particle structures as well as lower resolution maps determined by subtomogram averaging. Confidence maps represent a conservative way of interpreting molecular structures owing to minimized noise. At the same time they provide a detection error with respect to background noise, which is associated with the density and is particularly beneficial for the interpretation of weaker cryo-EM densities in cases of conformational flexibility and lower occupancy of bound molecules and ions in the structure.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000455767600004
%$ pmid:30713700
%R 10.1107/S2052252518014434
%U https://juser.fz-juelich.de/record/858495