The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.

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...

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Main Authors: Zheng Wang, Renzhi Cao, Kristen Taylor, Aaron Briley, Charles Caldwell, Jianlin Cheng
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3594155?pdf=render
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author Zheng Wang
Renzhi Cao
Kristen Taylor
Aaron Briley
Charles Caldwell
Jianlin Cheng
author_facet Zheng Wang
Renzhi Cao
Kristen Taylor
Aaron Briley
Charles Caldwell
Jianlin Cheng
author_sort Zheng Wang
collection DOAJ
description 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.
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spelling doaj.art-03ff365a6e06493292ee1fcb5ee70fb02022-12-22T00:18:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5879310.1371/journal.pone.0058793The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.Zheng WangRenzhi CaoKristen TaylorAaron BrileyCharles CaldwellJianlin ChengThe 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.http://europepmc.org/articles/PMC3594155?pdf=render
spellingShingle Zheng Wang
Renzhi Cao
Kristen Taylor
Aaron Briley
Charles Caldwell
Jianlin Cheng
The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.
PLoS ONE
title The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.
title_full The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.
title_fullStr The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.
title_full_unstemmed The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.
title_short The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.
title_sort properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types
url http://europepmc.org/articles/PMC3594155?pdf=render
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