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Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data.

Fortin JP, Hansen KD - Genome Biol. (2015)

Bottom Line: Analysis of Hi-C data has shown that the genome can be divided into two compartments called A/B compartments.These compartments are cell-type specific and are associated with open and closed chromatin.We do this by exploiting that the structure of long-range correlations differs between open and closed compartments.

View Article: PubMed Central - PubMed

Affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Road, Baltimore, 21205, MD, USA. fortin@jhsph.edu.

ABSTRACT
Analysis of Hi-C data has shown that the genome can be divided into two compartments called A/B compartments. These compartments are cell-type specific and are associated with open and closed chromatin. We show that A/B compartments can reliably be estimated using epigenetic data from several different platforms: the Illumina 450 k DNA methylation microarray, DNase hypersensitivity sequencing, single-cell ATAC sequencing and single-cell whole-genome bisulfite sequencing. We do this by exploiting that the structure of long-range correlations differs between open and closed compartments. This work makes A/B compartment assignment readily available in a wide variety of cell types, including many human cancers.

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Related in: MedlinePlus

Densities of the correlations of the 450 k methylation probes. Chromosome 14 was binned at resolution 100 kb and we display the binned, stratified correlations for the 450 k-EBV dataset. Each plot shows one density curve for each type of interaction: between two bins in open compartments, between two bins in closed compartments and between a bin in the open compartment and the closed compartment. a Binned correlations for open sea probes only. b Binned correlations for CpG resort probes only. Most correlations are around zero, except correlations between two open sea probes in the closed compartment. The open and closed compartments were defined using the HiC-EBV-2014 dataset
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Fig4: Densities of the correlations of the 450 k methylation probes. Chromosome 14 was binned at resolution 100 kb and we display the binned, stratified correlations for the 450 k-EBV dataset. Each plot shows one density curve for each type of interaction: between two bins in open compartments, between two bins in closed compartments and between a bin in the open compartment and the closed compartment. a Binned correlations for open sea probes only. b Binned correlations for CpG resort probes only. Most correlations are around zero, except correlations between two open sea probes in the closed compartment. The open and closed compartments were defined using the HiC-EBV-2014 dataset

Mentions: In Fig. 4, we show density plots of binned correlations on chromosome 14, stratified in two ways. The first stratification separates correlations between bins that are both in the open compartment or both in the closed compartment, and also cross-compartment correlations. This stratification shows that we have a large number of intermediate correlation values (0.2–0.5), but only between bins that are both in the closed compartment. The second stratification separates open sea probes and CpG resort probes (probes within 4 kb of a CpG island; see “Materials and methods”). This stratification shows that we only have intermediate correlation values for open sea probes; CpG resort probes are generally uncorrelated. In conclusion, we have the following structure of the binned correlation matrix: most of the matrix contains correlation values around zero (slightly positive), except between two bins both in the closed compartment, which have an intermediate correlation value of 0.2–0.5. This shows why an eigen analysis of the binned correlation matrix recovers the open and closed compartments; see Fig. 5 for an illustration.Fig. 4


Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data.

Fortin JP, Hansen KD - Genome Biol. (2015)

Densities of the correlations of the 450 k methylation probes. Chromosome 14 was binned at resolution 100 kb and we display the binned, stratified correlations for the 450 k-EBV dataset. Each plot shows one density curve for each type of interaction: between two bins in open compartments, between two bins in closed compartments and between a bin in the open compartment and the closed compartment. a Binned correlations for open sea probes only. b Binned correlations for CpG resort probes only. Most correlations are around zero, except correlations between two open sea probes in the closed compartment. The open and closed compartments were defined using the HiC-EBV-2014 dataset
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4574526&req=5

Fig4: Densities of the correlations of the 450 k methylation probes. Chromosome 14 was binned at resolution 100 kb and we display the binned, stratified correlations for the 450 k-EBV dataset. Each plot shows one density curve for each type of interaction: between two bins in open compartments, between two bins in closed compartments and between a bin in the open compartment and the closed compartment. a Binned correlations for open sea probes only. b Binned correlations for CpG resort probes only. Most correlations are around zero, except correlations between two open sea probes in the closed compartment. The open and closed compartments were defined using the HiC-EBV-2014 dataset
Mentions: In Fig. 4, we show density plots of binned correlations on chromosome 14, stratified in two ways. The first stratification separates correlations between bins that are both in the open compartment or both in the closed compartment, and also cross-compartment correlations. This stratification shows that we have a large number of intermediate correlation values (0.2–0.5), but only between bins that are both in the closed compartment. The second stratification separates open sea probes and CpG resort probes (probes within 4 kb of a CpG island; see “Materials and methods”). This stratification shows that we only have intermediate correlation values for open sea probes; CpG resort probes are generally uncorrelated. In conclusion, we have the following structure of the binned correlation matrix: most of the matrix contains correlation values around zero (slightly positive), except between two bins both in the closed compartment, which have an intermediate correlation value of 0.2–0.5. This shows why an eigen analysis of the binned correlation matrix recovers the open and closed compartments; see Fig. 5 for an illustration.Fig. 4

Bottom Line: Analysis of Hi-C data has shown that the genome can be divided into two compartments called A/B compartments.These compartments are cell-type specific and are associated with open and closed chromatin.We do this by exploiting that the structure of long-range correlations differs between open and closed compartments.

View Article: PubMed Central - PubMed

Affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Road, Baltimore, 21205, MD, USA. fortin@jhsph.edu.

ABSTRACT
Analysis of Hi-C data has shown that the genome can be divided into two compartments called A/B compartments. These compartments are cell-type specific and are associated with open and closed chromatin. We show that A/B compartments can reliably be estimated using epigenetic data from several different platforms: the Illumina 450 k DNA methylation microarray, DNase hypersensitivity sequencing, single-cell ATAC sequencing and single-cell whole-genome bisulfite sequencing. We do this by exploiting that the structure of long-range correlations differs between open and closed compartments. This work makes A/B compartment assignment readily available in a wide variety of cell types, including many human cancers.

Show MeSH
Related in: MedlinePlus