A Multigraph-Based Representation of Hi-C Data

Genes (Basel). 2022 Nov 23;13(12):2189. doi: 10.3390/genes13122189.

Abstract

Chromatin-chromatin interactions and three-dimensional (3D) spatial structures are involved in transcriptional regulation and have a decisive role in DNA replication and repair. To understand how individual genes and their regulatory elements function within the larger genomic context, and how the genome reacts to environmental stimuli, the linear sequence information needs to be interpreted in three-dimensional space, which is still a challenging task. Here, we propose a novel, heuristic approach to represent Hi-C datasets by a whole-genomic pseudo-structure in 3D space. The baseline of our approach is the construction of a multigraph from genomic-sequence data and Hi-C interaction data, then applying a modified force-directed layout algorithm. The resulting layout is a pseudo-structure. While pseudo-structures are not based on direct observation and their details are inherent to settings, surprisingly, they demonstrate interesting, overall similarities of known genome structures of both barley and rice, namely, the Rabl and Rosette-like conformation. It has an exciting potential to be extended by additional omics data (RNA-seq, Chip-seq, etc.), allowing to visualize the dynamics of the pseudo-structures across various tissues or developmental stages. Furthermore, this novel method would make it possible to revisit most Hi-C data accumulated in the public domain in the last decade.

Keywords: DNA; Hi-C; barley; graph theory; rice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin Immunoprecipitation Sequencing
  • Chromatin* / genetics
  • Chromosomes*
  • Genome / genetics
  • Genomics / methods

Substances

  • Chromatin

Grants and funding

This research was funded by research grants from the National Research, Development and Innovation Office (NKFIH-FK-124266 and NKFIH-K-129221). TKP2021-NKTA-06 was implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-NKTA funding scheme.