期刊
NUCLEIC ACIDS RESEARCH
卷 43, 期 7, 页码 3465-3477出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkv221
关键词
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资金
- Spanish Ministerio de Economia y Competitividad [BFU2010-19310, BFU2013-47736-P, BIO2007-61762]
- European Research Council [609989, 232913]
- Human Frontiers Science Program [RGP0044]
- Spanish Instituto de Salud Carlos III [PI10/01702]
- Fundacion Marcelino Botin
- ERC Synergy [609989]
- European Research Council (ERC) [609989, 232913] Funding Source: European Research Council (ERC)
- ICREA Funding Source: Custom
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.
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