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. 2023 Jul 5;51(W1):W5-W10.
doi: 10.1093/nar/gkad354.

3D-GNOME 3.0: a three-dimensional genome modelling engine for analysing changes of promoter-enhancer contacts in the human genome

Michal Wlasnowolski  1   2 , Michal Kadlof  1 , Kaustav Sengupta  1   2 , Dariusz Plewczynski  1   2
Affiliations

3D-GNOME 3.0: a three-dimensional genome modelling engine for analysing changes of promoter-enhancer contacts in the human genome

Michal Wlasnowolski et al. Nucleic Acids Res. .

Abstract

In the current update, we added a feature for analysing changes in spatial distances between promoters and enhancers in chromatin 3D model ensembles. We updated our datasets by the novel in situ CTCF and RNAPII ChIA-PET chromatin loops obtained from the GM12878 cell line mapped to the GRCh38 genome assembly and extended the 1000 Genomes SVs dataset. To handle the new datasets, we applied GPU acceleration for the modelling engine, which gives a speed-up of 30× versus the previous versions. To improve visualisation and data analysis, we embedded the IGV tool for viewing ChIA-PET arcs with additional genes and SVs annotations. For 3D model visualisation, we added a new viewer: NGL, where we provided colouring by gene and enhancer location. The models are downloadable in mmcif and xyz format. The web server is hosted and performs calculations on DGX A100 GPU servers that provide optimal performance with multitasking. 3D-GNOME 3.0 web server provides unique insights into the topological mechanism of human variations at the population scale with high speed-up and is freely available at https://3dgnome.mini.pw.edu.pl/.

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Figures

Graphical Abstract
Graphical Abstract
Below we attached the caption for the graphical abstract:3D-GNOME 3.0: a three-dimensional genome modelling engine for analysing changes of promoter-enhancer contacts in the human genome.
Figure 1.
Figure 1.
Scheme of 3D-GNOME 3.0 server architecture.
Figure 2.
Figure 2.
Results for the region chr14:35605439–35615196: (A) Screenshot of the IGV browser showing CTCF-mediated (green) and RNAPII-mediated (purple) chromatin interactions, as well as genomic annotations for the selected region. Tracks 1–2 display arcs for the reference cell line (GM12878), tracks 3–4 show SVs mapped to the reference genome, and tracks 5–8 show the arcs for variant I and variant II, respectively. Track 9 shows the genes located in the selected locus. (B) 3D chromatin models reconstructed for the selected region for the reference cell line (left) and variant II (right) based on CTCF interactions (up) and CTCF + RNAPII interactions (down). (C) A responsive table of the distances between the NFKBIA gene and enhancers in the reference and variant. (D) Box plots of the distance distribution between the NFKBIA gene and enhancer located in the chr14:35046634–35048014 region for the reference and variant 2.
See this image and copyright information in PMC

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