Predicting chromosomal compartments directly from the nucleotide sequence with DNA-DDA

Three-dimensional (3D) genome architecture is characterized by multi-scale patterns and plays an essential role in gene regulation. Chromatin conformation capturing experiments have revealed many properties underlying 3D genome architecture, such as the compartmentalization of chromatin based on transcriptional states. However, they are complex, costly and time consuming, and therefore only a limited number of cell types have been examined using these techniques. Increasing effort is being directed towards deriving computational methods that can predict chromatin conformation and associated structures. Here we present DNA-delay differential analysis (DDA), a purely sequence-based method based on chaos theory to predict genome-wide A and B compartments. We show that DNA-DDA models derived from a 20 Mb sequence are sufficient to predict genome wide compartmentalization at the scale of 100 kb in four different cell types. Although this is a proof-of-concept study, our method shows promise in elucidating the mechanisms responsible for genome folding as well as modeling the impact of genetic variation on 3D genome architecture and the processes regulated thereby.