Journal Article FZJ-2018-07367

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Thresholding of cryo-EM density maps by false discovery rate control

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2019
Chester

IUCrJ 6(1), 1-16 () [10.1107/S2052252518014434]

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Abstract: 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.

Classification:

Contributing Institute(s):
  1. Strukturbiologie (ER-C-3)
Research Program(s):
  1. 899 - ohne Topic (POF3-899) (POF3-899)

Appears in the scientific report 2019
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Medline ; Creative Commons Attribution CC BY 4.0 ; DOAJ ; OpenAccess ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2018-12-13, last modified 2021-01-30