Perspectives for the reconstruction of 3D chromatin conformation using single cell Hi-C data

PLoS Comput Biol. 2021 Nov 18;17(11):e1009546. doi: 10.1371/journal.pcbi.1009546. eCollection 2021 Nov.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Chromatin / chemistry*
  • Mice
  • Protein Conformation
  • Single-Cell Analysis / methods*

Substances

  • Chromatin

Grants and funding

PIK is supported by Skoltech Systems Biology fellowship. AAG is supported by RFBR grant 19-34-90136. The work of SVU is supported by the Russian Science Foundation grant 21-64-00001. SVU and SVR were supported by the Interdisciplinary Scientific and Educational School of Moscow University ‘Molecular Technologies of the Living Systems and Synthetic Biology’. MSG is supported by RFBR grant 18-29-13011. AVC is supported by RFBR grant 18-29-13041. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.