Large-scale data-driven and physics-based models offer insights into the relationships among the structures, dynamics, and functions of chromosomes.

Abstract

The organized three-dimensional chromosome architecture in the cell nucleus provides scaffolding for precise regulation of gene expression. When the cell changes its identity in the cell-fate decision-making process, extensive rearrangements of chromosome structures occur accompanied by large-scale adaptations of gene expression, underscoring the importance of chromosome dynamics in shaping genome function. Over the last two decades, rapid development of experimental methods has provided unprecedented data to characterize the hierarchical structures and dynamic properties of chromosomes. In parallel, these enormous data offer valuable opportunities for developing quantitative computational models. Here, we review a variety of large-scale polymer models developed to investigate the structures and dynamics of chromosomes. Different from the underlying modeling strategies, these approaches can be classified into data-driven ('top-down') and physics-based ('bottom-up') categories. We discuss their contributions to offering valuable insights into the relationships among the structures, dynamics, and functions of chromosomes and propose the perspective of developing data integration approaches from different experimental technologies and multidisciplinary theoretical/simulation methods combined with different modeling strategies.