SpectralTAD: an R package for defining a hierarchy of topologically associated domains using spectral clustering.

BMC Bioinformatics
Kellen G CresswellMikhail G Dozmorov

Abstract

The three-dimensional (3D) structure of the genome plays a crucial role in gene expression regulation. Chromatin conformation capture technologies (Hi-C) have revealed that the genome is organized in a hierarchy of topologically associated domains (TADs), sub-TADs, and chromatin loops. Identifying such hierarchical structures is a critical step in understanding genome regulation. Existing tools for TAD calling are frequently sensitive to biases in Hi-C data, depend on tunable parameters, and are computationally inefficient. To address these challenges, we developed a novel sliding window-based spectral clustering framework that uses gaps between consecutive eigenvectors for TAD boundary identification. Our method, implemented in an R package, SpectralTAD, detects hierarchical, biologically relevant TADs, has automatic parameter selection, is robust to sequencing depth, resolution, and sparsity of Hi-C data. SpectralTAD outperforms four state-of-the-art TAD callers in simulated and experimental settings. We demonstrate that TAD boundaries shared among multiple levels of the TAD hierarchy were more enriched in classical boundary marks and more conserved across cell lines and tissues. In contrast, boundaries of TADs that cannot be...Continue Reading

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Datasets Mentioned

BETA
GM12878

Methods Mentioned

BETA
Hi-C
ICE

Software Mentioned

HiCSeg
SpectralTAD R
rGMAP
rGREAT
OnTAD
HiCToolsCompare
Juicer
HiCExplorer
HiGlass
UCSC genome browser

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