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Review
. 2020 Oct 1:181-182:24-34.
doi: 10.1016/j.ymeth.2019.08.008. Epub 2019 Aug 27.

Computational approaches for inferring 3D conformations of chromatin from chromosome conformation capture data

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Review

Computational approaches for inferring 3D conformations of chromatin from chromosome conformation capture data

Dario Meluzzi et al. Methods. .

Abstract

Chromosome conformation capture (3C) and its variants are powerful experimental techniques for probing intra- and inter-chromosomal interactions within cell nuclei at high resolution and in a high-throughput, quantitative manner. The contact maps derived from such experiments provide an avenue for inferring the 3D spatial organization of the genome. 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.

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Figures

Figure 1:
Figure 1:
Schematic of the overall pipeline for studying 3D organization of chromatin using 3C technology. The primary topic of this review article on computational methods for recovering 3D structure and structure populations of chromatin from 2D contact maps is highlighted by the dashed box. The maps themselves are generated from the sequences of read pairs, which are in turn collected from crosslinked chromatin in a large ensemble of cells.
Figure 2:
Figure 2:
General scheme for computational methods that rely on distance-optimization to generate a consensus structure that is consistent with an experimental contact map. Blocks represent the main components common to these methods. Arrows represent the main flow of information. Not all methods attempt to optimize the parameters of the relation used to convert contact frequencies into inter-locus distances.
Figure 3:
Figure 3:
General scheme for computational methods that use polymer physics to generate an ensemble of structures that is consistent with an experimental contact map. Blocks represent the main components common to these methods. Arrows represent the main flow of information.
Figure 4:
Figure 4:
General scheme for computational methods that use maximum likelihood or Bayesian inference to generate a consensus structure or an ensemble of structures, respectively, that is consistent with an experimental contact map. Blocks represent the main components common to these methods. Arrows represent the main flow of information.

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