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Hierarchical Domain Structure Reveals the Divergence of Activity among TADs and Boundaries

Lin An, Tao Yang, Jiahao Yang, Johannes Nuebler, Guanjue Xiang, Ross C. Hardison, Qunhua Li, Yu Zhang
doi: https://doi.org/10.1101/361147
Lin An
1Bioinformatics and Genomics program, Pennsylvania State University, University Park, PA
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Tao Yang
1Bioinformatics and Genomics program, Pennsylvania State University, University Park, PA
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Jiahao Yang
2Tsinghua University, Beijing, China
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Johannes Nuebler
3Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA
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Guanjue Xiang
1Bioinformatics and Genomics program, Pennsylvania State University, University Park, PA
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Ross C. Hardison
4Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA
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Qunhua Li
5Department of Statistics, Pennsylvania State University, University Park, PA
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  • For correspondence: yzz2@psu.edu
Yu Zhang
5Department of Statistics, Pennsylvania State University, University Park, PA
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  • For correspondence: yzz2@psu.edu
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Abstract

The spatial organization of chromatin in the nucleus has been implicated in many aspects of regulated gene expression. Maps of high frequency interactions between different segments of chromatin have revealed Topologically Associating Domains (TADs), within which most of the regulatory interactions are thought to occur. Recent studies have shown that TADs are not homogeneous structural units, but rather they appear to be organized into a hierarchy. However, precise identification of hierarchical TAD structures remains a challenge. We present OnTAD, an Optimized Nested TAD caller from Hi-C data, to identify hierarchical TADs. Compared to existing methods, OnTAD has significantly improved accuracy and running speed. Results from OnTAD reveal new biological insights on the role of different TAD levels, boundary usage in gene regulation, the loop extrusion model, and compartmental domains. The software and documentation for OnTAD are available at: https://github.com/anlin00007/OnTAD

Footnotes

  • Email addresses: LA: lua137{at}psu.edu; TY: txy146{at}psu.edu; JY: yangjh14{at}mails.tsinghua.edu.cn; JN: jnuebler{at}mit.edu; RH: rch8{at}psu.edu; QL: qunhua.li{at}psu.edu; YZ: yzz2{at}psu.edu.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 26, 2019.
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Hierarchical Domain Structure Reveals the Divergence of Activity among TADs and Boundaries
Lin An, Tao Yang, Jiahao Yang, Johannes Nuebler, Guanjue Xiang, Ross C. Hardison, Qunhua Li, Yu Zhang
bioRxiv 361147; doi: https://doi.org/10.1101/361147
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Hierarchical Domain Structure Reveals the Divergence of Activity among TADs and Boundaries
Lin An, Tao Yang, Jiahao Yang, Johannes Nuebler, Guanjue Xiang, Ross C. Hardison, Qunhua Li, Yu Zhang
bioRxiv 361147; doi: https://doi.org/10.1101/361147

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