M-free : scoring the reference bias in sub-tomogram averaging and template matching

Cryo-electron tomography provides a snapshot of the cellular proteome. With template matching, the spatial positions of various macromolecular complexes within their native cellular context can be detected. However, the 
Cryo-electron tomography provides a snapshot of the cellular proteome. With template matching, the spatial positions of various macromolecular complexes within their native cellular context can be detected. However, the growing awareness of the reference bias introduced by the cross-correlation based approaches, and more importantly the lack of a reliable confidence measurement in the selection of these macromolecular complexes, has restricted the use of these applications. Here we propose a heuristic, in which the reference bias is measured in real space in an analogous way to the R-free value in X-ray crystallography. We measure the reference bias within the mask used to outline the area of the template, and do not modify the template itself. The heuristic works by splitting the mask into a working and a testing area in a volume ratio of 9:1. While the working area is used during the calculation of the cross-correlation function, the information from both areas is explored to calculate the M-free score. We show using artificial data, that the M-free score gives a reliable measure for the reference bias. The heuristic can be applied in template matching and in sub-tomogram averaging. We further test the applicability of the heuristic in tomograms of purified macromolecules, and tomograms of whole Mycoplasma cells.
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Metadaten
Author:Zhou Yu, Achilleas S. Frangakis
URN:urn:nbn:de:hebis:30:3-353988
DOI:http://dx.doi.org/10.1016/j.jsb.2014.05.007
ISSN:1095-8657
ISSN:1047-8477
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24859794
Parent Title (English):Journal of structural biology
Publisher:Elsevier
Place of publication:San Diego
Document Type:Article
Language:English
Year of Completion:2014
Date of first Publication:2014/05/22
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/10/28
Tag:assessment of reference bias; reference bias; sub-tomogram averaging; template bias; template matching
Volume:187
Issue:1
Pagenumber:10
First Page:10
Last Page:19
Note:
(c) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
HeBIS PPN:36667627X
Institutes:Biowissenschaften
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0

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