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Hi-C: A Method to Study the Three-dimensional Architecture of Genomes.
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Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data.

Jean-Philippe Fortin1, Kasper D Hansen2,3

  • 1Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Road, Baltimore, 21205, MD, USA. fortin@jhsph.edu.

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Genome A/B compartments, linked to open or closed chromatin, can be reliably predicted using various epigenetic data. This method expands A/B compartment analysis to diverse cell types, including human cancers.

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Area of Science:

  • Genomics
  • Epigenetics
  • Computational Biology

Background:

  • The genome is organized into A/B compartments, reflecting open (A) and closed (B) chromatin states.
  • These compartments are cell-type specific and crucial for understanding genome regulation.
  • Hi-C data analysis is a primary method for identifying these compartments.

Purpose of the Study:

  • To demonstrate that A/B compartments can be reliably estimated using diverse epigenetic data platforms.
  • To provide a broadly applicable method for A/B compartment assignment across various cell types.

Main Methods:

  • Analysis of long-range correlation structures in epigenetic data.
  • Utilizing data from Illumina 450 k DNA methylation microarray.
  • Employing DNase hypersensitivity sequencing, single-cell ATAC sequencing, and single-cell whole-genome bisulfite sequencing.

Main Results:

  • Epigenetic data from multiple platforms accurately predict genome A/B compartments.
  • Differences in long-range correlation structures distinguish open and closed chromatin compartments.
  • Successful A/B compartment assignment was achieved across various cell types.

Conclusions:

  • A/B compartment estimation is feasible and reliable using readily available epigenetic data.
  • This approach significantly broadens the accessibility of A/B compartment analysis.
  • The method is applicable to a wide range of cell types, including human cancers, facilitating further research in these areas.