title: Assessing the limits of restraint-based 3D modeling of genomes and genomic domains.
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.
authors: EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors: Marie
authors: http://orcid.org/0000-0002-7258-7272
authors: M
authors: Trussart
authors: Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Barcelona, Spain Genome Biology Group, Centre Nacional d'Anàlisi Genòmica (CNAG), Barcelona, Spain.
authors: François
authors: F
authors: Serra
authors: Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Barcelona, Spain Genome Biology Group, Centre Nacional d'Anàlisi Genòmica (CNAG), Barcelona, Spain.
authors: Davide
authors: D
authors: Baù
authors: Universitat Pompeu Fabra (UPF), Barcelona, Spain Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Barcelona, Spain.
authors: Ivan
authors: I
authors: Junier
authors: EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors: Luís
authors: L
authors: Serrano
authors: Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Barcelona, Spain Genome Biology Group, Centre Nacional d'Anàlisi Genòmica (CNAG), Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain mmarti@pcb.ub.cat.
authors: Marc A
authors: http://orcid.org/0000-0002-0151-4279
authors: MA
authors: Marti-Renom
mesh_terms: D016678:Genome; D008957:Models, Genetic