Hierarchical chromatin organization detected by TADpole

The rapid development of chromosome conformation capture (3C-based) techniques as well as super-resolution imaging together with bioinformatics analyses has been fundamental for unveiling that chromosomes are organized into the so-called topologically associating domains or TADs. While these TADs ap...

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Bibliographic Details
Published inbioRxiv
Main Authors Soler-Vila, Paula, Pol Cusco Pons, Farabella, Irene, Marco Di Stefano, Marti-Renom, Marc
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 11.07.2019
Subjects
Bioinformatics
Chromatin
Chromosomes
Cohesin
Computer applications
Conformation
Image processing
Principal components analysis
Statistical analysis
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Summary:The rapid development of chromosome conformation capture (3C-based) techniques as well as super-resolution imaging together with bioinformatics analyses has been fundamental for unveiling that chromosomes are organized into the so-called topologically associating domains or TADs. While these TADs appear as nested patterns in the 3C-based interaction matrices, the vast majority of available computational methods are based on the hypothesis that TADs are individual and unrelated chromatin structures. Here we introduce TADpole, a computational tool designed to identify and analyze the entire hierarchy of TADs in intra-chromosomal interaction matrices. TADpole combines principal component analysis and constrained hierarchical clustering to provide an unsupervised set of significant partitions in a genomic region of interest. TADpole identification of domains is robust to the data resolution, normalization strategy, and sequencing depth. TADpole domain borders are enriched in CTCF and cohesin binding proteins, while the domains are enriched in either H3K36me3 or H3k27me3 histone marks. We show TADpole usefulness by applying it to capture Hi-C experiments in wild-type and mutant mouse strains to pinpoint statistically significant differences in their topological structure. Footnotes * https://github.com/3DGenomes/TADpole
DOI:10.1101/698720