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

Przemyslaw Szalaj , Zhonghui Tang , Paul Michalski , Michal J. Pietal , Oscar J. Luo , Michal Sadowski , X. Li , Kamen Radew , Yijun Ruan , Dariusz Plewczyński


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.

Author Przemyslaw Szalaj - [University of Warsaw, Centre of New Technologies]
Przemyslaw Szalaj,,
, Zhonghui Tang - [Jackson Laboratory]
Zhonghui Tang,,
, Paul Michalski - [Jackson Laboratory]
Paul Michalski,,
, Michal J. Pietal - [University of Warsaw, Centre of New Technologies]
Michal J. Pietal,,
, Oscar J. Luo - [Jackson Laboratory]
Oscar J. Luo,,
, Michal Sadowski - [University of Warsaw, Centre of New Technologies]
Michal Sadowski,,
, X. Li - [Jackson Laboratory]
X. Li,,
, Kamen Radew - [University of Warsaw, Centre of New Technologies]
Kamen Radew,,
, Yijun Ruan - [Jackson Laboratory]
Yijun Ruan,,
, Dariusz Plewczyński (FMIS / DIPS)
Dariusz Plewczyński,,
- Department of Information Processing Systems
Journal seriesGenome Research, ISSN 1088-9051, e-ISSN 1549-5469
Issue year2016
ASJC Classification2716 Genetics(clinical); 1311 Genetics
Languageen angielski
Score (nominal)50
Score sourcejournalList
ScoreMinisterial score = 50.0, 04-06-2020, ArticleFromJournal
Ministerial score (2013-2016) = 50.0, 04-06-2020, ArticleFromJournal
Publication indicators Scopus Citations = 20; WoS Citations = 14; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 2.398; WoS Impact Factor: 2016 = 11.922 (2) - 2016=13.795 (5)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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