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Inferring Single-Cell 3D Chromosomal Structures Based on the Lennard-Jones Potential

Reconstructing three-dimensional (3D) chromosomal structures based on single-cell Hi-C data is a challenging scientific problem due to the extreme sparseness of the single-cell Hi-C data. In this research, we used the Lennard-Jones potential to reconstruct both 500 kb and high-resolution 50 kb chrom...

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Detalles Bibliográficos
Autores principales: Zha, Mengsheng, Wang, Nan, Zhang, Chaoyang, Wang, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199262/
https://www.ncbi.nlm.nih.gov/pubmed/34072879
http://dx.doi.org/10.3390/ijms22115914
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author Zha, Mengsheng
Wang, Nan
Zhang, Chaoyang
Wang, Zheng
author_facet Zha, Mengsheng
Wang, Nan
Zhang, Chaoyang
Wang, Zheng
author_sort Zha, Mengsheng
collection PubMed
description Reconstructing three-dimensional (3D) chromosomal structures based on single-cell Hi-C data is a challenging scientific problem due to the extreme sparseness of the single-cell Hi-C data. In this research, we used the Lennard-Jones potential to reconstruct both 500 kb and high-resolution 50 kb chromosomal structures based on single-cell Hi-C data. A chromosome was represented by a string of 500 kb or 50 kb DNA beads and put into a 3D cubic lattice for simulations. A 2D Gaussian function was used to impute the sparse single-cell Hi-C contact matrices. We designed a novel loss function based on the Lennard-Jones potential, in which the [Formula: see text] value, i.e., the well depth, was used to indicate how stable the binding of every pair of beads is. For the bead pairs that have single-cell Hi-C contacts and their neighboring bead pairs, the loss function assigns them stronger binding stability. The Metropolis–Hastings algorithm was used to try different locations for the DNA beads, and simulated annealing was used to optimize the loss function. We proved the correctness and validness of the reconstructed 3D structures by evaluating the models according to multiple criteria and comparing the models with 3D-FISH data.
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spelling pubmed-81992622021-06-14 Inferring Single-Cell 3D Chromosomal Structures Based on the Lennard-Jones Potential Zha, Mengsheng Wang, Nan Zhang, Chaoyang Wang, Zheng Int J Mol Sci Article Reconstructing three-dimensional (3D) chromosomal structures based on single-cell Hi-C data is a challenging scientific problem due to the extreme sparseness of the single-cell Hi-C data. In this research, we used the Lennard-Jones potential to reconstruct both 500 kb and high-resolution 50 kb chromosomal structures based on single-cell Hi-C data. A chromosome was represented by a string of 500 kb or 50 kb DNA beads and put into a 3D cubic lattice for simulations. A 2D Gaussian function was used to impute the sparse single-cell Hi-C contact matrices. We designed a novel loss function based on the Lennard-Jones potential, in which the [Formula: see text] value, i.e., the well depth, was used to indicate how stable the binding of every pair of beads is. For the bead pairs that have single-cell Hi-C contacts and their neighboring bead pairs, the loss function assigns them stronger binding stability. The Metropolis–Hastings algorithm was used to try different locations for the DNA beads, and simulated annealing was used to optimize the loss function. We proved the correctness and validness of the reconstructed 3D structures by evaluating the models according to multiple criteria and comparing the models with 3D-FISH data. MDPI 2021-05-31 /pmc/articles/PMC8199262/ /pubmed/34072879 http://dx.doi.org/10.3390/ijms22115914 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zha, Mengsheng
Wang, Nan
Zhang, Chaoyang
Wang, Zheng
Inferring Single-Cell 3D Chromosomal Structures Based on the Lennard-Jones Potential
title Inferring Single-Cell 3D Chromosomal Structures Based on the Lennard-Jones Potential
title_full Inferring Single-Cell 3D Chromosomal Structures Based on the Lennard-Jones Potential
title_fullStr Inferring Single-Cell 3D Chromosomal Structures Based on the Lennard-Jones Potential
title_full_unstemmed Inferring Single-Cell 3D Chromosomal Structures Based on the Lennard-Jones Potential
title_short Inferring Single-Cell 3D Chromosomal Structures Based on the Lennard-Jones Potential
title_sort inferring single-cell 3d chromosomal structures based on the lennard-jones potential
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199262/
https://www.ncbi.nlm.nih.gov/pubmed/34072879
http://dx.doi.org/10.3390/ijms22115914
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