How do genomes fit into the tiny confines of a cell nucleus? Genomes can be massive and making it more difficult, is that the genome may be repackaged across different biological dimensions and contexts such as cell types, developmental stages, disease states or points in time. Furthermore, it is not well understood which pieces of the genome control gene expression. Intrigued by this puzzle, researchers Sushmita Roy and recently graduated student, Da-Inn Lee introduce a powerful new computational tool in their latest study that could help systematically examine how DNA is arranged and how it changes across different dimensions.