Computational models of large-scale genome architecture.

The spatial architecture and dynamics of the genomic material in the limited volume of the nucleus plays an important role in biological processes ranging from gene expression to DNA repair. Yet, detailed descriptions of dynamic genome architecture are still lacking and its governing principles and functional implications remain largely unknown. Powerful experimental methods have been developed to address this gap, including single-cell imaging and chromosome conformation capture methods, leading to rapidly growing quantitative data sets. Despite their importance, however, these data are insufficient to provide a full understanding of genome architecture and function. Computational models are becoming an increasingly indispensable complement in order to make sense of the experimental data and to allow a quantitative understanding of how chromosomes fold, move and interact. Here, we review efforts, developed over the last ~25 years, to model the large-scale 3D organization and dynamics of chromosomes or genomes quantitatively. We discuss models based on theories and simulations of polymer physics or computational reconstruction methods, highlighting similarities and differences between models, as well as limitations and possible improvements.