Assessing the limits of restraint-based 3D modeling of genomes and genomic domains

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  • dc.contributor.author Trussart, Marie, 1985-ca
  • dc.contributor.author Serra, Françoisca
  • dc.contributor.author Baù, Davideca
  • dc.contributor.author Junier, Ivanca
  • dc.contributor.author Serrano Pubull, Luis, 1982-ca
  • dc.contributor.author Martí Renom, Marc A.ca
  • dc.date.accessioned 2015-11-17T14:58:06Z
  • dc.date.available 2015-11-17T14:58:06Z
  • dc.date.issued 2015
  • dc.description.abstract Restraint-based modeling of genomes has been recently explored with the advent of Chromosome Conformation Capture (3C-based) experiments. We previously developed a reconstruction method to resolve the 3D architecture of both prokaryotic and eukaryotic genomes using 3C-based data. These models were congruent with fluorescent imaging validation. However, the limits of such methods have not systematically been assessed. Here we propose the first evaluation of a mean-field restraint-based reconstruction of genomes by considering diverse chromosome architectures and different levels of data noise and structural variability. The results show that: first, current scoring functions for 3D reconstruction correlate with the accuracy of the models; second, reconstructed models are robust to noise but sensitive to structural variability; third, the local structure organization of genomes, such as Topologically Associating Domains, results in more accurate models; fourth, to a certain extent, the models capture the intrinsic structural variability in the input matrices and fifth, the accuracy of the models can be a priori predicted by analyzing the properties of the interaction matrices. In summary, our work provides a systematic analysis of the limitations of a mean-field restrain-based method, which could be taken into consideration in further development of methods as well as their applications.ca
  • dc.description.sponsorship Spanish Ministerio de Economía y Competitividad [BFU2010–19310, BFU2013–47736-P to M.A.M.-R., BIO2007–61762 to L.S.]; European Research Council [609989 to M.A.M.-R., 232913 to L.S.]; Human Frontiers Science Program [RGP0044 to M.A.M.-R.]; Spanish Instituto de Salud Carlos III [PI10/01702 to L.S.]; Fundación Marcelino Botin (to L.S.). Funding for open access charge: ERC Synergy [609989].en
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Trussart M, Serra F, Baù D, Junier I, Serrano L, Marti-Renom MA. Assessing the limits of restraint-based 3D modeling of genomes and genomic domains. Nucleic acids research. 2015;43(7):3465-77. DOI: 10.1093/nar/gkv221ca
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkv221
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/25117
  • dc.language.iso engca
  • dc.publisher Oxford University Pressca
  • dc.relation.ispartof Nucleic acids research. 2015;43(7):3465-77
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/232913
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2010-19310
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-47736
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/BIO2007-61762
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
  • dc.rights © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/ca
  • dc.subject.other Cromosomes
  • dc.subject.other Imatges tridimensionals
  • dc.subject.other Molècules -- Models -- Simulació per ordinador
  • dc.title Assessing the limits of restraint-based 3D modeling of genomes and genomic domainsca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

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