Si-C is a method for inferring super-resolution intact genome structure from single-cell Hi-C data

Luming Meng (), Chenxi Wang, Yi Shi and Qiong Luo
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Luming Meng: South China Normal University
Chenxi Wang: South China Normal University
Yi Shi: Shanghai Jiao Tong University
Qiong Luo: South China Normal University

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract There is a strong demand for methods that can efficiently reconstruct valid super-resolution intact genome 3D structures from sparse and noise single-cell Hi-C data. Here, we develop Single-Cell Chromosome Conformation Calculator (Si-C) within the Bayesian theory framework and apply this approach to reconstruct intact genome 3D structures from single-cell Hi-C data of eight G1-phase haploid mouse ES cells. The inferred 100-kb and 10-kb structures consistently reproduce the known conserved features of chromatin organization revealed by independent imaging experiments. The analysis of the 10-kb resolution 3D structures reveals cell-to-cell varying domain structures in individual cells and hyperfine structures in domains, such as loops. An average of 0.2 contact reads per divided bin is sufficient for Si-C to obtain reliable structures. The valid super-resolution structures constructed by Si-C demonstrate the potential for visualizing and investigating interactions between all chromatin loci at the genome scale in individual cells.

Date: 2021
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DOI: 10.1038/s41467-021-24662-z

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