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Combining genome-wide structural models with phenomenological data is at theforefront of efforts to understand the organizational principles regulating thehuman genome. Here, we use chromosome-chromosome contact data asknowledge-based constraints for large-scale three-dimensional models of thehuman diploid genome. The resulting models remain minimally entangled andacquire several functional features that are observed in vivo and that werenever used as input for the model. We find, for instance, that gene-rich,active regions are drawn towards the nuclear center, while gene poor andlamina-associated domains are pushed to the periphery. These and otherproperties persist upon adding local contact constraints, suggesting theircompatibility with non-local constraints for the genome organization. Theresults show that suitable combinations of data analysis and physical modellingcan expose the unexpectedly rich functionally-related properties implicit inchromosome-chromosome contact data. Specific directions are suggested forfurther developments based on combining experimental data analysis and genomicstructural modelling.

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