From 2D to 4D: a Containerized Workflow and Browser to Explore Dynamic Chromatin Architecture.

Area of Science:

• Genomics
• Computational Biology
• Molecular Biology

Background:

• Understanding genome physical organization is crucial for gene regulation and epigenetic accessibility.
• Hi-C experiments provide 2D contact maps but lack the resolution for 3D genome structure interpretation.
• Integrating 3D genome structure with functional and temporal (4D) data is key to understanding genome regulation.

Purpose of the Study:

• To present the 4D Genome Browser Workflow (4DGBWorkflow) and 4D Genome Browser (4DGB).
• To provide an accessible, end-to-end workflow for transforming, filtering, and visualizing 4D epigenomics and chromatin datasets.
• To enable non-specialists to apply 3D modeling principles to diverse datasets.

Main Methods:

• Utilizing the 4DHiC method as the algorithmic basis.
• Developing a containerized, end-to-end workflow executable on standard laptops (macOS, Linux, Windows).
• Integrating Hi-C data with molecular dynamics simulations and physical constraints for 3D genome reconstruction.

Main Results:

• The 4DGBWorkflow produces 3D chromosome reconstructions from Hi-C files.
• The workflow integrates reconstructions with epigenetic and transcriptome track data.
• Comparative visualization of 4D epigenomics and chromatin architecture is provided within a single workflow.

Conclusions:

• The 4DGBWorkflow and 4D Genome Browser are open-source tools for comparative analysis and visualization of 4D chromosome datasets.
• Automatic integration of Hi-C data with molecular dynamics simplifies the construction of time-resolved 3D genome structures.
• These tools democratize the analysis of chromatin architecture and epigenomic signals over time.