Inferring the three-dimensional structures of the X-chromosome during X-inactivation

Hao Zhu; Nan Wang; Jonathan Z. Sun; Ras B. Pandey; Zheng Wang; Hao Zhu; Nan Wang; Jonathan Z. Sun; Ras B. Pandey; Zheng Wang

doi:10.3934/mbe.2019369

Mathematical Biosciences and Engineering

2019, Volume 16, Issue 6: 7384-7404. doi: 10.3934/mbe.2019369

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Inferring the three-dimensional structures of the X-chromosome during X-inactivation

1.
Department of Computer Science, University of Miami, 1364 Memorial Drive, Coral Gables, FL 33124, USA
2.
Department of Computer Science, New Jersey City University, 2039 Kennedy Blvd, Jersey City, NJ 07305, USA
3.
Department of Computer Science, College of Charleston, Charleston, SC 29424, USA
4.
Department of Physics and Astronomy, University of Southern Mississippi, 118 College Drive #5046, Hattiesburg, MS 39406, USA

Received: 28 February 2019 Accepted: 25 July 2019 Published: 12 August 2019

The Hi-C experiment can capture the genome-wide spatial proximities of the DNA, based on which it is possible to computationally reconstruct the three-dimensional (3D) structures of chromosomes. The transcripts of the long non-coding RNA (lncRNA) Xist spread throughout the entire X-chromosome and alter the 3D structure of the X-chromosome, which also inactivates one copy of the two X-chromosomes in a cell. The Hi-C experiments are expensive and time-consuming to conduct, but the Hi-C data of the active and inactive X-chromosomes are available. However, the Hi-C data of the X-chromosome during the process of X-chromosome inactivation (XCI) are not available. Therefore, the 3D structure of the X-chromosome during the process of X-chromosome inactivation (XCI) remains to be unknown. We have developed a new approach to reconstruct the 3D structure of the X-chromosome during XCI, in which the chain of DNA beads representing a chromosome is stored and simulated inside a 3D cubic lattice. A 2D Gaussian function is used to model the zero values in the 2D Hi-C contact matrices. By applying simulated annealing and Metropolis-Hastings simulations, we first generated the 3D structures of the X-chromosome before and after XCI. Then, we used Xist localization intensities on the X-chromosome (RAP data) to model the traveling speeds or acceleration between all bead pairs during the process of XCI. The 3D structures of the X-chromosome at 3 hours, 6 hours, and 24 hours after the start of the Xist expression, which initiates the XCI process, have been reconstructed. The source code and the reconstructed 3D structures of the X-chromosome can be downloaded from http://dna.cs.miami.edu/3D-XCI/.
- 3D genome,
- 3D cubic lattice,
- simulation,
- Xist,
- lncRNA,
- X-chromosome inactivation
Citation: Hao Zhu, Nan Wang, Jonathan Z. Sun, Ras B. Pandey, Zheng Wang. Inferring the three-dimensional structures of the X-chromosome during X-inactivation[J]. Mathematical Biosciences and Engineering, 2019, 16(6): 7384-7404. doi: 10.3934/mbe.2019369

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Abstract

The Hi-C experiment can capture the genome-wide spatial proximities of the DNA, based on which it is possible to computationally reconstruct the three-dimensional (3D) structures of chromosomes. The transcripts of the long non-coding RNA (lncRNA) Xist spread throughout the entire X-chromosome and alter the 3D structure of the X-chromosome, which also inactivates one copy of the two X-chromosomes in a cell. The Hi-C experiments are expensive and time-consuming to conduct, but the Hi-C data of the active and inactive X-chromosomes are available. However, the Hi-C data of the X-chromosome during the process of X-chromosome inactivation (XCI) are not available. Therefore, the 3D structure of the X-chromosome during the process of X-chromosome inactivation (XCI) remains to be unknown. We have developed a new approach to reconstruct the 3D structure of the X-chromosome during XCI, in which the chain of DNA beads representing a chromosome is stored and simulated inside a 3D cubic lattice. A 2D Gaussian function is used to model the zero values in the 2D Hi-C contact matrices. By applying simulated annealing and Metropolis-Hastings simulations, we first generated the 3D structures of the X-chromosome before and after XCI. Then, we used Xist localization intensities on the X-chromosome (RAP data) to model the traveling speeds or acceleration between all bead pairs during the process of XCI. The 3D structures of the X-chromosome at 3 hours, 6 hours, and 24 hours after the start of the Xist expression, which initiates the XCI process, have been reconstructed. The source code and the reconstructed 3D structures of the X-chromosome can be downloaded from http://dna.cs.miami.edu/3D-XCI/.

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