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

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

Research output: Contribution to journalArticle

1 Scopus citations

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 languageEnglish (US)
Pages (from-to)7384-7404
Number of pages21
JournalMathematical Biosciences and Engineering
Volume16
Issue number6
DOIs
StatePublished - 2019

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

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