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/.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7384-7404 |
| Number of pages | 21 |
| Journal | Mathematical Biosciences and Engineering |
| Volume | 16 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- 3D cubic lattice
- 3D genome
- LncRNA
- Simulation
- X-chromosome inactivation
- Xist
ASJC Scopus subject areas
- Modeling and Simulation
- Agricultural and Biological Sciences(all)
- Computational Mathematics
- Applied Mathematics
Cite this
Inferring the three-dimensional structures of the X-chromosome during X-inactivation. / Zhu, Hao; Wang, Nan; Sun, Jonathan Z.; Pandey, Ras B.; Wang, Zheng.
In: Mathematical Biosciences and Engineering, Vol. 16, No. 6, 01.01.2019, p. 7384-7404.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inferring the three-dimensional structures of the X-chromosome during X-inactivation
AU - Zhu, Hao
AU - Wang, Nan
AU - Sun, Jonathan Z.
AU - Pandey, Ras B.
AU - Wang, Zheng
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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/.
AB - 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/.
KW - 3D cubic lattice
KW - 3D genome
KW - LncRNA
KW - Simulation
KW - X-chromosome inactivation
KW - Xist
UR - http://www.scopus.com/inward/record.url?scp=85070832320&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070832320&partnerID=8YFLogxK
U2 - 10.3934/mbe.2019369
DO - 10.3934/mbe.2019369
M3 - Article
C2 - 31698618
AN - SCOPUS:85070832320
VL - 16
SP - 7384
EP - 7404
JO - Mathematical Biosciences and Engineering
JF - Mathematical Biosciences and Engineering
SN - 1547-1063
IS - 6
ER -