Investigating human chromosome organization by whole-genome simulations*

In recent years, both theoreticians and experimentalists have dedicated significant effort to studying chromosome organization and its relation to gene expression and regulation. Many experimental procedures were designed, such as Hi-C, to capture the dynamic information of chromosome structure. Several theoretical models were then proposed to try to understand the principles underlying chromosome compartmentalization. In this work, we use the Open-MiChroM software to simulate the whole genome of GM12878 human cells at 50 kbp resolution. At this scale, 121,504 beads are necessary to model all 46 chromosomes, creating challenges of convergence and proper sampling of the ensemble of structures due to the size of the system. To address this, we performed analysis on the chromosome contacts and the correlation between states during the simulation, estimating the necessary number of replicas and sampling interval to perform the computations. The whole-genome simulations provide insights into inter-chromosome interactions and the relative distribution of chromosomes within the nucleus. Additionally, they also allow further investigation of the dynamics of phase separation of A/B compartments over time.