Predicting 3D genome architecture directly from the nucleotide sequence with DNA-DDA

3D genome architecture is characterized by multi-scale patterns and plays an essential role in proper cellular function. Chromatin conformation capturing experiments have revealed many properties underlying 3D genome architecture. 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-DDA, a purely sequence-based method that relies on nonlinear dynamics to predict genome-wide chromatin contacts and A/B compartments. We show that the DNA sequence and A/B compartment labels of a 20Mbp-long region of the human genome is sufficient to predict the 3D architecture of the entire genome. 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.