TADtree

TADtree identifies hierarchical topologically associating domains (TADs) and nested sub-TADs from Hi-C contact frequency matrices to characterize three-dimensional genome organization relevant to gene regulation and differentiation.

Key Features:

• Hierarchical Detection: Identifies nested TADs and sub-TADs rather than assuming non-overlapping domains.
• Model-Based Approach: Decomposes contact frequencies into a hierarchy of nested TADs using a statistical model based on empirical distributions of contact frequencies.
• Enhanced Contact Enrichment Analysis: Distinguishes inner and outer TADs by exploiting the observation that contact enrichment increases with genomic distance and is stronger for inner TADs in a pair.

Scientific Applications:

• Genomic Research: Characterizes spatial genome organization from Hi-C data to support studies of gene regulation and cellular differentiation.
• Boundary Enrichment Analysis: Detects TAD boundaries enriched for chromatin marks such as CTCF to study regulatory element interactions.

Methodology:

Uses a model that decomposes Hi-C contact frequencies into nested hierarchical domains by leveraging empirical distributions of contact frequencies and the observed increase in contact enrichment with genomic distance, distinguishing inner versus outer TAD enrichment.