A Multigraph model of the 3D genome

ABSTRACT Spatial organisation of the genome has a fundamental effect on its biological functions. Chromatin-chromatin interactions and 3D spatial structures are involved in transcriptional regulation and have a decisive role in DNA replication and repair. To understand how individual genes and their regulatory elements function within the larger genomic context, and how the genome reacts as a whole to environmental stimuli, the linear sequence information needs to be interpreted in 3-dimensional space. While recent advances in chromatin conformation capture technologies including Hi-C, considerably advanced our understanding of the genomes, defining the DNA, as it is organized in the cell nucleus is still a challenging task. 3D genome modelling needs to reflect the DNA as a flexible polymer, which can wind up to the fraction of its total length and greatly unwind and stretch to implement a multitude of functions. Here we propose a novel approach to model genomes as a multigraph based on Hi-C contact data. Multigraph-based 3D genome modelling of barley and rice revealed the well-known Rabl and Rosetta chromatin organizations, respectively, as well as other higher order structures. Our results shows that the well-established toolset of Graph theory is highly valuable in modelling large genomes in 3D.