A Polymer Model for the Quantitative Reconstruction of Chromosome Architecture from HiC and GAM Data.
Biophys J
; 115(12): 2286-2294, 2018 12 18.
Article
em En
| MEDLINE
| ID: mdl-30527448
ABSTRACT
It is widely believed that the folding of the chromosome in the nucleus has a major effect on genetic expression. For example, coregulated genes in several species have been shown to colocalize in space despite being far away on the DNA sequence. In this manuscript, we present a new, to our knowledge, method to model the three-dimensional structure of the chromosome in live cells based on DNA-DNA interactions measured in high-throughput chromosome conformation capture experiments and genome architecture mapping. Our approach incorporates a polymer model and directly uses the contact probabilities measured in high-throughput chromosome conformation capture experiments and genome architecture mapping experiments rather than estimates of average distances between genomic loci. Specifically, we model the chromosome as a Gaussian polymer with harmonic interactions and extract the coupling coefficients best reproducing the experimental contact probabilities. In contrast to existing methods, we give an exact expression of the contact probabilities at thermodynamic equilibrium. The Gaussian effective model reconstructed with our method reproduces experimental contacts with high accuracy. We also show how Brownian dynamics simulations of our reconstructed Gaussian effective model can be used to study chromatin organization and possibly give some clue about its dynamics.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Modelos Moleculares
/
Cromossomos
/
Genômica
Tipo de estudo:
Health_economic_evaluation
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2018
Tipo de documento:
Article