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Reassessing the Revolution’s Resolutions

Marin van Heel, Michael Schatz
doi: https://doi.org/10.1101/224402
Marin van Heel
1Brazilian Nanotechnology National Laboratory (LNNano), Brazilian Center for Research in Energy and Materials (CNPEM), 13083-970 Campinas, São Paulo, Brazil.
2Netherlands Centre for Electron Nanoscopy (NeCEN), 2333 CC Leiden, Netherlands.
3Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK.
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Michael Schatz
4Image Science Software GmbH, Gillweg 3, D-14193 Berlin, Germany.
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Abstract

We are currently facing an avalanche of cryo-EM (cryogenic Electron Microscopy) publications presenting beautiful structures at resolution levels of ~3Å: a true “resolution revolution” [Kühlbrandt, Science 343(2014)1443-1444]. Impressive as these results may be, a fundamental statistical error has persisted in the literature that affects the numerical resolution values for practically all published structures. The error goes back to a misinterpretation of basic statistics and pervades virtually all popular cryo-EM quality metrics. The resolution in cryo-EM is typically assessed by the Fourier Shell Correlation “FSC” [Harauz & van Heel: Optik 73(1986)146-156] using a fixed threshold value of 0.143 (“FSC0.143”) [Rosenthal, Henderson, J. Mol. Biol. 333(2003)721–745]. Using a simple model experiment we illustrate why this fixed threshold is flawed and we pinpoint the source of the resolution confusion. When two vectors are uncorrelated the expectation value of their inner-product is zero. That, however, does not imply that each individual inner-product of the vectors is zero (the vectors are not orthogonal). This error was introduced to electron microscopy in [Frank & Al-Ali, Nature 256(1975)376-379] and has since proliferated into virtually all quality and resolution-related metrics in EM. One criterion not affected by this error is the information-based ½-bit FSC threshold [van Heel & Schatz: J. Struct. Biol. 151(2005)250-262].

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 24, 2017.
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Reassessing the Revolution’s Resolutions
Marin van Heel, Michael Schatz
bioRxiv 224402; doi: https://doi.org/10.1101/224402
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Reassessing the Revolution’s Resolutions
Marin van Heel, Michael Schatz
bioRxiv 224402; doi: https://doi.org/10.1101/224402

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