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Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization

View ORCID ProfileMarco Di Stefano, Jonas Paulsen, Tonje G. Lien, View ORCID ProfileEivind Hovig, View ORCID ProfileCristian Micheletti
doi: https://doi.org/10.1101/079558
Marco Di Stefano
1SISSA, International School for Advanced Studies, Trieste, I-34136, Italy
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  • For correspondence: marco.distefano@cnag.crg.eu
Jonas Paulsen
2Institute of Basic Medical Sciences, University of Oslo, Oslo, 0317, Norway
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Tonje G. Lien
3University of Oslo, Department of Mathematics, Oslo, 0316, Norway
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Eivind Hovig
4Institute for Cancer Research, Oslo University Hospital, Department of Tumor Biology, Oslo, 0310, Norway
5University of Oslo, Department of Informatics, Oslo, 0316, Norway
6Institute of Cancer Genetics and Informatics, Oslo, 0310, Norway
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Cristian Micheletti
1SISSA, International School for Advanced Studies, Trieste, I-34136, Italy
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ABSTRACT

Combining genome-wide structural models with phenomenological data is at the forefront of efforts to understand the organizational principles regulating the human genome. Here, we use chromosome-chromosome contact data as knowledge- based constraints for large-scale three-dimensional models of the human diploid genome. The resulting models remain minimally entangled and acquire several functional features that are observed in vivo and that were never used as input for the model. We find, for instance, that gene-rich, active regions are drawn towards the nuclear center, while gene poor and lamina-associated domains are pushed to the periphery. These and other properties persist upon adding local contact constraints, suggesting their compatibility with non-local constraints for the genome organization. The results show that suitable combinations of data analysis and physical modelling can expose the unexpectedly rich functionally-related properties implicit in chromosome-chromosome contact data. Specific directions are suggested for further developments based on combining experimental data analysis and genomic structural modelling.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 17, 2016.
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Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization
Marco Di Stefano, Jonas Paulsen, Tonje G. Lien, Eivind Hovig, Cristian Micheletti
bioRxiv 079558; doi: https://doi.org/10.1101/079558
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Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization
Marco Di Stefano, Jonas Paulsen, Tonje G. Lien, Eivind Hovig, Cristian Micheletti
bioRxiv 079558; doi: https://doi.org/10.1101/079558

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