An integrated 3-Dimensional Genome Modeling Engine for data-driven simulation of spatial genome organization

• DOI: 10.1101/gr.205062.116
• Publication Date: 2016-10-28T02:13:38Z
• Authors: Przemysław Szałaj; Zhonghui Tang; Paul Michalski; Michal J. Pietal; Oscar J. Luo; Michał Sadowski; Xingwang Li; Kamen Radew; Yijun Ruan; Dariusz Plewczynski
• Keywords: Chromosome conformation capture; CTCF

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 gene regulation mediated by specific protein factors. Recently, we showed single experiment information at all genomic scales interest, from high-resolution locations binding sites enriched factors, to low resolution nonenriched reflect topological neighborhoods higher-order chromosome folding. This multilevel nature data offers an opportunity use multiscale 3D models study structural-functional relationships multiple length scales, but doing so requires structural modeling platform. Here, report development 3D-GNOME ( 3 - D imensional G e no me M odeling E ngine ), complete computational pipeline for simulation using data. consists three integrated components: graph-distance-based heat map normalization tool, platform, interactive visualization tool. Using Hi-C derived human B-lymphocytes, demonstrate effectiveness in building levels, including entire genome, individual chromosomes, segments megabase (Mb) kilobase (kb) resolutions average ensemble structures. Further incorporation CTCF-motif orientation looping patterns provided additional reliability potential biologically plausible