RT Journal Article
SR Electronic
T1 Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 079558
DO 10.1101/079558
A1 Marco Di Stefano
A1 Jonas Paulsen
A1 Tonje G. Lien
A1 Eivind Hovig
A1 Cristian Micheletti
YR 2016
UL http://biorxiv.org/content/early/2016/10/17/079558.abstract
AB 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.