Abstract
Construction of chromosomes 3D models based on single cell Hi-C data constitute an important challenge. We present a reconstruction approach, DPDchrom, that incorporates basic knowledge whether the reconstructed conformation should be coil-like or globular and spring relaxation at contact sites. In contrast to previously published protocols, DPDchrom can naturally form globular conformation due to the presence of explicit solvent. Benchmarking of this and several other methods on artificial polymer models reveals similar reconstruction accuracy at high contact density and DPDchrom advantage at low contact density. To compare 3D structures insensitively to spatial orientation and scale, we propose the Modified Jaccard Index. We analyzed two sources of the contact dropout: contact radius change and random contact sampling. We found that the reconstruction accuracy exponentially depends on the number of contacts per genomic bin allowing to estimate the reconstruction accuracy in advance. We applied DPDchrom to model chromosome configurations based on single-cell Hi-C data of mouse oocytes and found that these configurations differ significantly from a random one, that is consistent with other studies.
Highlights
The levels of DNA packaging, such as chromatin compartments [1], topologically associating domains (TADs) [2], and loops, are largely conserved between different cell types [3]
Reconstruction of 3D configuration of chromosomes based on single cell Hi-C data constitutes an important way to understand the specific features of genome packaging in individual cells
We develop method DPDchrom based on dissipative particle dynamics
Summary
The levels of DNA packaging, such as chromatin compartments [1], topologically associating domains (TADs) [2], and loops, are largely conserved between different cell types [3]. The conformation of chromosomes in individual cells varies significantly [4]. There are two main experimental approaches to study the spatial chromatin organization: methods based on chromosome conformation capture (for a review see [5]) and microscopy techniques (fluorescent in situ hybridization [6], live-cell imaging [7], etc.). The all vs all version of chromosome conformation capture, Hi-C, remains a key source of knowledge about the chromatin structure averaged over the population of cells [1, 9]. Developed single-cell and single-nucleus Hi-C approaches capture contacts in individual cells or nuclei [4, 10,11,12], opening up a unique opportunity to bridge the gap between Hi-C and microscopy
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