title: Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization.
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.
authors: SISSA, International School for Advanced Studies, Trieste, I-34136, Italy.
authors: Marco
authors: M
authors: Di Stefano
authors: Institute of Basic Medical Sciences, University of Oslo, Oslo, 0317, Norway.
authors: Jonas
authors: J
authors: Paulsen
authors: University of Oslo, Department of Mathematics, Oslo, 0316, Norway.
authors: Tonje G
authors: TG
authors: Lien
authors: Institute for Cancer Research, Oslo University Hospital, Department of Tumor Biology, Oslo, 0310, Norway.|University of Oslo, Department of Informatics, Oslo, 0316, Norway.|Institute of Cancer Genetics and Informatics, Oslo, 0310, Norway.
authors: Eivind
authors: E
authors: Hovig
authors: SISSA, International School for Advanced Studies, Trieste, I-34136, Italy.
authors: Cristian
authors: C
authors: Micheletti
mesh_terms: D002460:Cell Line; D020090:Chromosome Segregation / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics* / Q000648:ultrastructure; D030541:Databases, Genetic; D004171:Diploidy; D005347:Fibroblasts / Q000648:ultrastructure; D015894:Genome, Human; D000066449:Human Embryonic Stem Cells / Q000648:ultrastructure; D006801:Humans; D021621:Imaging, Three-Dimensional; D008957:Models, Genetic