Show simple item record

dc.contributor.authorHimes, Benjamin A.
dc.contributor.authorGrigorieff, Nikolaus
dc.date2022-08-11T08:08:26.000
dc.date.accessioned2022-08-23T15:55:17Z
dc.date.available2022-08-23T15:55:17Z
dc.date.issued2021-02-19
dc.date.submitted2021-03-17
dc.identifier.citation<p>bioRxiv 2021.02.19.431636; doi: https://doi.org/10.1101/2021.02.19.431636. <a href="https://doi.org/10.1101/2021.02.19.431636" target="_blank" title="view preprint in bioRxiv">Link to preprint on bioRxiv.</a></p>
dc.identifier.doi10.1101/2021.02.19.431636
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29720
dc.description<p>This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.</p>
dc.description.abstractImage simulation plays a central role in the development and practice of high-resolution electron microscopy, including transmission electron microscopy of frozen-hydrated specimens (cryo-EM). Simulating images with contrast that matches the contrast observed in experimental images remains challenging, especially for amorphous samples. Current state-of-the-art simulators apply post hoc scaling to approximate empirical solvent contrast, attenuated image intensity due to specimen thickness, and amplitude contrast. This practice fails for images that require spatially variable scaling, e.g., simulations of a crowded or cellular environment. Modeling both the signal and the noise accurately is necessary to simulate images of biological specimens with contrast that is correct on an absolute scale. To do so, we introduce the “Frozen-Plasmon” method which explicitly models spatially variable inelastic scattering processes in cryo-EM specimens. This approach produces amplitude contrast that depends on the atomic composition of the specimen, reproduces the total inelastic mean free path as observed experimentally and allows for the incorporation of radiation damage in the simulation. Taken in combination with a new mathematical formulation for accurately sampling the tabulated atomic scattering potentials onto a Cartesian grid, we also demonstrate how the matched-filter concept can be used to quantitatively compare model and experiment. The simulator is available as a standalone program, implemented in C++ with multi-threaded parallelism using the computational imaging system for Transmission Electron Microscopy (cisTEM.)
dc.language.isoen_US
dc.rightsThe 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 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectbiophysics
dc.subjectCryo-TEM simulations
dc.subjectimage simulation
dc.subjectBiophysics
dc.titleCryo-TEM simulations of amorphous radiation-sensitive samples using multislice wave propagation [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2945&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1932
dc.identifier.contextkey22087153
refterms.dateFOA2022-08-23T15:55:17Z
html.description.abstract<p><p id="x-x-x-x-p-2">Image simulation plays a central role in the development and practice of high-resolution electron microscopy, including transmission electron microscopy of frozen-hydrated specimens (cryo-EM). Simulating images with contrast that matches the contrast observed in experimental images remains challenging, especially for amorphous samples. Current state-of-the-art simulators apply post hoc scaling to approximate empirical solvent contrast, attenuated image intensity due to specimen thickness, and amplitude contrast. This practice fails for images that require spatially variable scaling, <em>e.g.</em>, simulations of a crowded or cellular environment. Modeling both the signal and the noise accurately is necessary to simulate images of biological specimens with contrast that is correct on an absolute scale. To do so, we introduce the “Frozen-Plasmon” method which explicitly models spatially variable inelastic scattering processes in cryo-EM specimens. This approach produces amplitude contrast that depends on the atomic composition of the specimen, reproduces the total inelastic mean free path as observed experimentally and allows for the incorporation of radiation damage in the simulation. Taken in combination with a new mathematical formulation for accurately sampling the tabulated atomic scattering potentials onto a Cartesian grid, we also demonstrate how the matched-filter concept can be used to quantitatively compare model and experiment. The simulator is available as a standalone program, implemented in C++ with multi-threaded parallelism using the computational imaging system for Transmission Electron Microscopy (<em>cis</em>TEM.)</p>
dc.identifier.submissionpathfaculty_pubs/1932
dc.contributor.departmentRNA Therapeutics Institute


Files in this item

Thumbnail
Name:
2021.02.19.431636v1.full.pdf
Size:
1.035Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

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 4.0 International license.
Except where otherwise noted, this item's license is described as 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 4.0 International license.