# RobusTAD: reference panel based annotation of nested topologically associating domains

## TL;DR

This paper introduces RobusTAD, a new method for accurately identifying and organizing nested TADs in 3D genome structures using Hi-C data.

## Contribution

RobusTAD improves TAD boundary annotation and hierarchy inference by leveraging reference panel data.

## Key findings

- RobusTAD outperforms existing tools in boundary detection and domain annotation.
- Incorporating additional Hi-C data refines TAD annotations in study samples.

## Abstract

Topologically associating domains (TADs) are fundamental units of 3D genomes and play essential roles in gene regulation. Hi-C data suggests a hierarchical organization of TADs. Accurately annotating nested TADs from Hi-C data remains challenging, both in terms of the precise identification of boundaries and the correct inference of hierarchies. While domain boundary is relatively well conserved across cells, few approaches have taken advantage of this fact. Here, we present RobusTAD to annotate TAD hierarchies. It incorporates additional Hi-C data to refine boundaries annotated from the study sample. RobusTAD outperforms existing tools at boundary and domain annotation across several benchmarking tasks.

The online version contains supplementary material available at 10.1186/s13059-025-03568-9.