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GenomeFlow: a comprehensive graphical tool for modeling and analyzing 3D genome structure

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Bioinformatics

Oxford University Press

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      Abstract

      MotivationThree-dimensional (3D) genome organization plays important functional roles in cells. User-friendly tools for reconstructing 3D genome models from chromosomal conformation capturing data and analyzing them are needed for the study of 3D genome organization.ResultsWe built a comprehensive graphical tool (GenomeFlow) to facilitate the entire process of modeling and analysis of 3D genome organization. This process includes the mapping of Hi-C data to one-dimensional (1D) reference genomes, the generation, normalization and visualization of two-dimensional (2D) chromosomal contact maps, the reconstruction and the visualization of the 3D models of chromosome and genome, the analysis of 3D models and the integration of these models with functional genomics data. This graphical tool is the first of its kind in reconstructing, storing, analyzing and annotating 3D genome models. It can reconstruct 3D genome models from Hi-C data and visualize them in real-time. This tool also allows users to overlay gene annotation, gene expression data and genome methylation data on top of 3D genome models.Availability and implementationThe source code and user manual: https://github.com/jianlin-cheng/GenomeFlow.Supplementary information Supplementary data are available at Bioinformatics online.

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      Most cited references 12

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        Comprehensive mapping of long-range interactions reveals folding principles of the human genome.

        We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.
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          A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping.

          We use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ∼10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs "facing" one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Author and article information

            Affiliations
            Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO, USA
            Author notes
            To whom correspondence should be addressed. chengji@ 123456missouri.edu

            The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.

            Contributors
            Role: Associate Editor
            Journal
            Bioinformatics
            Bioinformatics
            bioinformatics
            Bioinformatics
            Oxford University Press
            1367-4803
            1367-4811
            15 April 2019
            12 September 2018
            12 September 2018
            : 35
            : 8
            : 1416-1418
            30215673
            6477968
            10.1093/bioinformatics/bty802
            bty802
            (Associate Editor)
            © The Author(s) 2018. Published by Oxford University Press.

            This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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            Pages: 3
            Product
            Categories
            Applications Notes
            Genome Analysis

            Bioinformatics & Computational biology

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