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dc.contributor.authorHofmann, A
dc.contributor.authorKrufczik, M
dc.contributor.authorHeermann, DW
dc.contributor.authorHausmann, M
dc.date.accessioned2019-07-04T12:33:23Z
dc.date.available2019-07-04T12:33:23Z
dc.date.issued2018
dc.identifier.issn1661-6596
dc.identifier.doi10.3390/ijms19082263
dc.identifier.urihttp://hdl.handle.net/10072/385252
dc.description.abstractDNA double strand breaks (DSB) are the most severe damages in chromatin induced by ionizing radiation. In response to such environmentally determined stress situations, cells have developed repair mechanisms. Although many investigations have contributed to a detailed understanding of repair processes, e.g., homologous recombination repair or non-homologous end-joining, the question is not sufficiently answered, how a cell decides to apply a certain repair process at a certain damage site, since all different repair pathways could simultaneously occur in the same cell nucleus. One of the first processes after DSB induction is phosphorylation of the histone variant H2AX to γH2AX in the given surroundings of the damaged locus. Since the spatial organization of chromatin is not random, it may be conclusive that the spatial organization of γH2AX foci is also not random, and rather, contributes to accessibility of special repair proteins to the damaged site, and thus, to the following repair pathway at this given site. The aim of this article is to demonstrate a new approach to analyze repair foci by their topology in order to obtain a cell independent method of categorization. During the last decade, novel super-resolution fluorescence light microscopic techniques have enabled new insights into genome structure and spatial organization on the nano-scale in the order of 10 nm. One of these techniques is single molecule localization microscopy (SMLM) with which the spatial coordinates of single fluorescence molecules can precisely be determined and density and distance distributions can be calculated. This method is an appropriate tool to quantify complex changes of chromatin and to describe repair foci on the single molecule level. Based on the pointillist information obtained by SMLM from specifically labeled heterochromatin and γH2AX foci reflecting the chromatin morphology and repair foci topology, we have developed a new analytical methodology of foci or foci cluster characterization, respectively, by means of persistence homology. This method allows, for the first time, a cell independent comparison of two point distributions (here the point distributions of two γH2AX clusters) with each other of a selected ensample and to give a mathematical measure of their similarity. In order to demonstrate the feasibility of this approach, cells were irradiated by low LET (linear energy transfer) radiation with different doses and the heterochromatin and γH2AX foci were fluorescently labeled by antibodies for SMLM. By means of our new analysis method, we were able to show that the topology of clusters of γH2AX foci can be categorized depending on the distance to heterochromatin. This method opens up new possibilities to categorize spatial organization of point patterns by parameterization of topological similarity.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto18
dc.relation.ispartofissue8
dc.relation.ispartofjournalInternational Journal of Molecular Sciences
dc.relation.ispartofvolume19
dc.subject.fieldofresearchOther Chemical Sciences
dc.subject.fieldofresearchGenetics
dc.subject.fieldofresearchOther Biological Sciences
dc.subject.fieldofresearchcode0399
dc.subject.fieldofresearchcode0604
dc.subject.fieldofresearchcode0699
dc.titleUsing persistent homology as a new approach for super-resolution localization microscopy data analysis and classification of γH2AX foci/clusters
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorHofmann, Andreas


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