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Updated: Mar 5, 2026

Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C
Published on: October 14, 2022
A critical assessment of topologically associating domain prediction tools
Rola Dali1, Mathieu Blanchette1
1School of Computer Science and McGill Centre for Bioinformatics, McGill University, Montreal, Canada.
Abstract:
Topologically associating domains (TADs) have been proposed to be the basic unit of chromosome folding and have been shown to play key roles in genome organization and gene regulation. Several different tools are available for TAD prediction, but their properties have never been thoroughly assessed. In this manuscript, we compare the output of seven different TAD prediction tools on two published Hi-C data sets. TAD predictions varied greatly between tools in number, size distribution and other biological properties. Assessed against a manual annotation of TADs, individual TAD boundary predictions were found to be quite reliable, but their assembly into complete TAD structures was much less so. In addition, many tools were sensitive to sequencing depth and resolution of the interaction frequency matrix. This manuscript provides users and designers of TAD prediction tools with information that will help guide the choice of tools and the interpretation of their predictions.
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