title: An integrated 3-Dimensional Genome Modeling Engine for data-driven simulation of spatial genome organization.
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.
authors: Centre of New Technologies, Warsaw University, 02-097 Warsaw, Poland.|Centre for Innovative Research, Medical University of Bialystok, 15-089 Białystok, Poland.|I-BioStat, Hasselt University, BE3590 Hasselt, Belgium.
authors: Przemysław
authors: P
authors: Szałaj
authors: The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA.
authors: Zhonghui
authors: Z
authors: Tang
authors: The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA.
authors: Paul
authors: P
authors: Michalski
authors: Centre of New Technologies, Warsaw University, 02-097 Warsaw, Poland.
authors: Michal J
authors: MJ
authors: Pietal
authors: The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA.
authors: Oscar J
authors: OJ
authors: Luo
authors: Centre of New Technologies, Warsaw University, 02-097 Warsaw, Poland.
authors: Michał
authors: M
authors: Sadowski
authors: The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA.
authors: Xingwang
authors: X
authors: Li
authors: Centre of New Technologies, Warsaw University, 02-097 Warsaw, Poland.
authors: Kamen
authors: K
authors: Radew
authors: The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA.|Department of Genetics and Genome Sciences, UConn Health, Farmington, Connecticut 06032, USA.
authors: Yijun
authors: Y
authors: Ruan
authors: Centre of New Technologies, Warsaw University, 02-097 Warsaw, Poland.|Centre for Innovative Research, Medical University of Bialystok, 15-089 Białystok, Poland.|Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland.
authors: Dariusz
authors: D
authors: Plewczynski
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics*; D002875:Chromosomes; D002877:Chromosomes, Human / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D005786:Gene Expression Regulation; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D016247:Information Storage and Retrieval; D008957:Models, Genetic
chemical_list: D002843:Chromatin