Visualization of chromosomal reorganization induced by heterologous fusions in the mammalian nucleus

Chromosomes are spatially organized and functionally folded into a specific macro-structure in the nucleus. Recently, we and others created haploid cells with chromosome fusions. However, there is still lack of an effective strategy for precisely investigating how the genome copes with fusions. Here, we developed a down-sampling method to convert the populational Hi-C dataset into single cell-like Khimaira Matrix (K-matrix). K-matrix preserves not only the most prominent functional genomic features but also cell-to-cell variations. K-matrix-originated genome 3D models display spatial approach of fused chromosomes and minor global structure alterations. Combined with a layered positional decomposition analysis, our models indicate slight re-adjustment of chromosome distributions accordingly with an increasing tendency following more fusions involved. Nevertheless, the radial distribution of the A/B compartment is not affected dramatically. By contrast, natural populations harboring Rb fusions display significant alterations of chromosome radial location. Overall, K-matrix-originated models enable visualization of chromosomal reorganization with high resolution.