Learning Genomic Energy Landscapes from Experiments

This chapter argues that the energy landscape theory, which has proven useful in understanding protein folding, and provides a powerful bridge between the top-down and bottom-up perspectives when thinking about chromosome structure and function. It describes a physical theory motivated by symmetry principles that explains how local interactions between genomic loci can lead to the conformations of human chromosomes in interphase. The principles learned using the energy landscape theory allow the construction of a force field that predicts detailed Hi-C data for many distinct human chromosomes, using epigenetic marks found through binding assays. While some argue that information theory is logically prior to physics, many others would hold that physics is prior to information theory. Genome-wide ligation assays measure the frequency at which any given pair of genomic segments in the chromosomes comes into close spatial proximity inside the nucleus.