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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/23159

Title: An integrated 3-dimensional genome modeling engine for data-driven simulation of spatial genome organization
Authors: Szałaj, Przemysław
Tang, Zhonghui
Michalski, Paul
Pietal, Michal J.
Luo, Oscar J.
Sadowski, Michał
Li, Xingwang
Radew, Kamen
Ruan, Yijun
Plewczynski, Dariusz
Issue Date: 2016
Citation: GENOME RESEARCH, 26(12), p. 1697-1709
Abstract: ChIA-PET is a high-throughput mapping technology that reveals long-range chromatin interactions and provides insights into the basic principles of spatial genome organization and gene regulation mediated by specific protein factors. Recently, we showed that a single ChIA-PET experiment provides information at all genomic scales of interest, from the high-resolution locations of binding sites and enriched chromatin interactions mediated by specific protein factors, to the low resolution of nonenriched interactions that reflect topological neighborhoods of higher-order chromosome folding. This multilevel nature of ChIA-PET data offers an opportunity to use multiscale 3D models to study structural-functional relationships at multiple length scales, but doing so requires a structural modeling platform. Here, we report the development of 3D-GNOME (3-Dimensional Genome Modeling Engine), a complete computational pipeline for 3D simulation using ChIA-PET data. 3D-GNOME consists of three integrated components: a graph-distance-based heat map normalization tool, a 3D modeling platform, and an interactive 3D visualization tool. Using ChIA-PET and Hi-C data derived from human B-lymphocytes, we demonstrate the effectiveness of 3D-GNOME in building 3D genome models at multiple levels, including the entire genome, individual chromosomes, and specific segments at megabase (Mb) and kilobase (kb) resolutions of single average and ensemble structures. Further incorporation of CTCF-motif orientation and high-resolution looping patterns in 3D simulation provided additional reliability of potential biologically plausible topological structures.
URI: http://hdl.handle.net/1942/23159
DOI: 10.1101/gr.205062.116
ISI #: 000389563000007
ISSN: 1088-9051
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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