The 3D ensemble of chromosome structures was predicted for the cell types (A) IMR90, (B) HUVEC, and (C) K562 using the ChIP-Seq histone modification tracks for the respective cell lines found on ENCODE—shown are the structural predictions for chromosome 2. As validation, the chromosome structures were compared with the DNA–DNA ligation experiments of Rao et al., 2014, where the simulated map is shown on the bottom left triangle and the experimental map is shown on the top right triangle. The datasets are visualized using Juicebox (Durand et al., 2016). The MEGABASE chromatin type annotation is shown as a color vector under the contact probability map, followed by the A/B compartment annotation (Rao et al., 2014) for the simulated map (red) and the experimental map (black), respectively. The Pearson’s R between the simulated and experimental contact maps for fixed genomic distances are plotted for the cell types IMR90, HUVEC, and K562, respectively, in thick lines. The Pearson’s R between the experimental maps of mismatching cell types are also shown with thin lines—See Legend. The shaded region highlights that at relatively short genomic distances (<10 Mb), excluding CTCF-mediated loops from the simulation results in disagreement between the simulated and experimental maps. When loops are included in the simulations, the agreement between the simulation and experiment is recovered at the short genomic distances. (D) Pearson’s R as a function of genomic distance is plotted between the experimental map for chromosome 21 (IMR90) and MiChroM simulation with loops (thick red line) and without loops (thin red line). (E) A matrix of Pearson’s R between the AB annotation of the experimental ligation map and the simulated contact maps for different cell types, respectively. The high Pearson’s R signifies the consistency between the simulated maps and the experimental DNA–DNA ligation maps. Additional comparisons between simulated and experimental DNA–DNA ligation maps are shown for cell lines HMEC, H1-hESC, and HeLa-S3 in Figure 1—figure supplements 1–3, respectively. A matrix of Pearson’s R between the AB annotation of the experimental ligation maps for different cell types is shown in Figure 1—figure supplement 4.