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It is widely believed that the folding of the chromosome in the nucleus has amajor effect on genetic expression. For example co-regulated genes in severalspecies have been shown to colocalize in space despite being far away on theDNA sequence. In this manuscript, we present a new method to model thethree-dimensional structure of the chromosome in live cells, based on DNA-DNAinteractions measured in high-throughput chromosome conformation captureexperiments (Hi-C) and genome architecture mapping experiments (GAM). Ourapproach incorporates a polymer model, and directly uses the contactprobabilities measured in Hi-C and GAM experiments rather than estimates ofaverage distances between genomic loci. Specifically, we model the chromosomeas a Gaussian polymer with harmonic interactions and extract the couplingcoefficients best reproducing the experimental contact probabilities. Incontrast to existing methods, we give an exact expression of the contactprobabilities at thermodynamic equilibrium. The Gaussian effective model (GEM)reconstructed with our method reproduces experimental contacts with highaccuracy. We also show how Brownian Dynamics simulations of our reconstructedGEM can be used to study chromatin organization, and possibly give some clueabout its dynamics.

A polymer model for the quantitative reconstruction of 3d chromosome architecture from Hi-C and GAM data