A Polymer Model for the Quantitative Reconstruction of Chromosome Architecture from HiC and GAM Data.

@article{LeTreut2018APM,
  title={A Polymer Model for the Quantitative Reconstruction of Chromosome Architecture from HiC and GAM Data.},
  author={Guillaume Le Treut and François K{\'e}p{\`e}s and Henri Orland},
  journal={Biophysical journal},
  year={2018},
  volume={115 12},
  pages={
          2286-2294
        }
}
It is widely believed that the folding of the chromosome in the nucleus has a major effect on genetic expression. [...] Key Result 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.Expand
Inference of chromosome 3D structures from GAM data by a physics computational approach.
TLDR
A method to reconstruct 3D structures from Genome Architecture Mapping (GAM) data, based on PRISMR, a computational approach introduced to find the minimal polymer model best describing Hi-C input data from only polymer physics is discussed.
Computational Elucidation of self-organization of E. coli chromosome underlying HI-C data
TLDR
The Hi-C data-integrated chromosome model elucidates a self-organised structure of E. coli chromosome into multiple macrodomains within ring-like architecture, with oriC loci located at the mid-cell position and the role of multiple nucleotide-associated proteins like HU, Fis and MatP in controlling the chromosome architecture is quantified.
From Hi-C Contact Map to Three-dimensional Organization of Interphase Human Chromosomes
TLDR
The HIPPS method shows that conformations of chromosomes are heterogeneous even in a single cell type, and the differences in the conformational heterogeneity of the same chromosome in different cell types can also be quantitatively discerned using the theory.
A Hi–C data-integrated model elucidates E. coli chromosome’s multiscale organization at various replication stages
TLDR
A beads-on-a-spring polymer-based framework with recently reported Hi–C data for E. coli chromosome is combined to develop a comprehensive model of its chromosome at 5 kb resolution, showing that it adopts helix-like conformation with no net chirality.
Toward understanding the dynamic state of 3D genome
TLDR
The recently developed PHi-C method is introduced, a computational tool for modeling the fluctuations of the 3D genome organization in the presence of stochastic thermal noise and another new method is presented that analyzes the dynamic rheology property (represented as microrheology spectra) as a measure of the flexibility and rigidity of genomic regions over time.
A unified framework for inferring the multi-scale organization of chromatin domains from Hi-C
TLDR
This physically principled interpretation and analysis of Hi-C not only offers an accurate and quantitative view of multi-scale chromatin organization but also helps decipher its connections with genome function.
Mapping the Multiscale Organisation of Escherichia Coli Chromosome in a Hi-C-integrated Model
TLDR
The present work, integrated with Hi-C interaction, elucidates the organization of bacterial chromosome at multiple scales, ranging from identifying a helical, macro-domain-segregated morphology at coarse-grained scale to a manifestation of CIDs at a fine- grained scale.
The Functional 3D Organization of Unicellular Genomes
TLDR
This work systematically applies the open-sourced framework, spatial-mHG, to search for spatial co-localization phenomena in multiple unicellular Hi-C datasets with corresponding genomic annotations, and shed new light on the functional spatial organization of genomes.
PHi-C: deciphering Hi-C data into polymer dynamics
TLDR
A 4D simulation method, PHi-C (polymer dynamics deciphered from Hi-C data), that depicts 4D genome features from 2D Hi- C data by polymer modeling and allows users to interpret 2DhiC data as physical interaction parameters within single chromosomes to demonstrate dynamic characteristics of genomic loci and chromosomes.
Computational Approaches for Inferring 3D Conformations of Chromatin from Chromosome Conformation Capture Data.
TLDR
This review provides an overview of the various computational methods developed in the past decade for addressing the very important but challenging problem of deducing the detailed 3D structure or structure population of chromosomal domains, chromosomes, and even entire genomes from 3C contact maps.
...
1
2
...

References

SHOWING 1-10 OF 77 REFERENCES
Inferential modeling of 3D chromatin structure
TLDR
A new Bayesian framework to derive the 3D architecture of a chromosome from 3C-based data is developed and an expectation-maximization (EM) based algorithm is proposed to estimate the unknown parameters of the Bayesian model and infer an ensemble of chromatin structures based on interaction frequency data.
The Three-Dimensional Architecture of a Bacterial Genome and Its Alteration by Genetic Perturbation
TLDR
The 3D architecture of the Caulobacter crescentus genome is determined by combining genome-wide chromatin interaction detection, live-cell imaging, and computational modeling, which suggest that genome folding is globally dictated by the parS sites and chromosome segregation.
Polymer physics of chromosome large-scale 3D organisation
TLDR
It is shown that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales.
Population-based 3D genome structure analysis reveals driving forces in spatial genome organization
TLDR
A probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells and incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states.
The three-dimensional architecture of a bacterial genome and its alteration by genetic perturbation.
TLDR
The 3D architecture of the Caulobacter crescentus genome is determined by combining genome-wide chromatin interaction detection, live-cell imaging, and computational modeling, which suggest that genome folding is globally dictated by the parS sites and chromosome segregation.
Spatially confined folding of chromatin in the interphase nucleus
TLDR
A polymer model able to describe key properties of chromatin over length scales ranging from 0.5 to 75 Mb is presented and can explain the observed data and suggests that on the tens-of-megabases length scale P is small, i.e., 10–30 loops per 100 Mb, sufficient to enforce folding inside the confined space of a chromosome territory.
Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
TLDR
Hi-C is described, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing and demonstrates the power of Hi-C to map the dynamic conformations of entire genomes.
Predictive Polymer Modeling Reveals Coupled Fluctuations in Chromosome Conformation and Transcription
TLDR
It is demonstrated that contacts between potential regulatory elements occur in the context of fluctuating structures rather than stable loops and proposed that such fluctuations may contribute to asymmetric expression in the Xic during X inactivation.
A Three-Dimensional Model of the Yeast Genome
TLDR
A method to globally capture intra- and inter-chromosomal interactions is developed and applied to generate a map at kilobase resolution of the haploid genome of Saccharomyces cerevisiae, which recapitulates known features of genome organization, thereby validating the method, and identifies new features.
Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization
TLDR
It is found that gene-rich, active regions are drawn towards the nuclear center, while gene poor and lamina associated domains are pushed to the periphery and these and other properties persist upon adding local contact constraints, suggesting their compatibility with non-local constraints for the genome organization.
...
1
2
3
4
5
...