title: The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.
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.
authors.affiliation: Computer Science Department, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Renzhi
authors.initials: R
authors.lastname: Cao
authors.forename: Kristen
authors.initials: K
authors.lastname: Taylor
authors.forename: Aaron
authors.initials: A
authors.lastname: Briley
authors.forename: Charles
authors.initials: C
authors.lastname: Caldwell
authors.forename: Jianlin
authors.initials: J
authors.lastname: Cheng
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods; D004843:Epistasis, Genetic; D053263:Gene Regulatory Networks; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D009690:Nucleic Acid Conformation; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D014157:Transcription Factors
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