SpectralTAD: an R package for defining a hierarchy of topologically associated domains using spectral clustering.
BMC Bioinformatics
; 21(1): 319, 2020 Jul 20.
Article
em En
| MEDLINE
| ID: mdl-32689928
ABSTRACT
BACKGROUND:
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.METHODS:
To address these challenges, we developed a novel sliding window-based spectral clustering framework that uses gaps between consecutive eigenvectors for TAD boundary identification.RESULTS:
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 split into sub-TADs showed less enrichment and conservation, suggesting their more dynamic role in genome regulation.CONCLUSION:
SpectralTAD is available on Bioconductor, http//bioconductor.org/packages/SpectralTAD/ .Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Algoritmos
/
Software
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Cromatina
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Genoma Humano
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Regulação da Expressão Gênica
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Biologia Computacional
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
BMC Bioinformatics
Assunto da revista:
INFORMATICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos