The Properties of Genome Conformation and Spatial Gene Interaction and Regulation Networks of Normal and Malignant Human Cell Types

Zheng Wang, Renzhi Cao, Kristen Taylor, Aaron Briley, Charles Caldwell, Jianlin Cheng

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The spatial conformation of a genome plays an important role in the long-range regulation of genome-wide gene expression and methylation, but has not been extensively studied due to lack of genome conformation data. The recently developed chromosome conformation capturing techniques such as the Hi-C method empowered by next generation sequencing can generate unbiased, large-scale, high-resolution chromosomal interaction (contact) data, providing an unprecedented opportunity to investigate the spatial structure of a genome and its applications in gene regulation, genomics, epigenetics, and cell biology. In this work, we conducted a comprehensive, large-scale computational analysis of this new stream of genome conformation data generated for three different human leukemia cells or cell lines by the Hi-C technique. We developed and applied a set of bioinformatics methods to reliably generate spatial chromosomal contacts from high-throughput sequencing data and to effectively use them to study the properties of the genome structures in one-dimension (1D) and two-dimension (2D). Our analysis demonstrates that Hi-C data can be effectively applied to study tissue-specific genome conformation, chromosome-chromosome interaction, chromosomal translocations, and spatial gene-gene interaction and regulation in a three-dimensional genome of primary tumor cells. Particularly, for the first time, we constructed genome-scale spatial gene-gene interaction network, transcription factor binding site (TFBS) - TFBS interaction network, and TFBS-gene interaction network from chromosomal contact information. Remarkably, all these networks possess the properties of scale-free modular networks.

Original languageEnglish (US)
Article numbere58793
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 11 2013
Externally publishedYes

Fingerprint

gene interaction
Conformations
Genes
Cells
Genome
genome
cells
binding sites
Transcription Factors
transcription factors
Chromosomes
Gene Regulatory Networks
Binding Sites
chromosomes
Gene expression
Genetic Translocation
genes
Genomics
Computational Biology
methodology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

The Properties of Genome Conformation and Spatial Gene Interaction and Regulation Networks of Normal and Malignant Human Cell Types. / Wang, Zheng; Cao, Renzhi; Taylor, Kristen; Briley, Aaron; Caldwell, Charles; Cheng, Jianlin.

In: PLoS One, Vol. 8, No. 3, e58793, 11.03.2013.

Research output: Contribution to journalArticle

Wang, Zheng ; Cao, Renzhi ; Taylor, Kristen ; Briley, Aaron ; Caldwell, Charles ; Cheng, Jianlin. / The Properties of Genome Conformation and Spatial Gene Interaction and Regulation Networks of Normal and Malignant Human Cell Types. In: PLoS One. 2013 ; Vol. 8, No. 3.
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