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

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. Constructing valid super-resolution intact genome 3D structures from single-cell Hi-C data is essential in investigating chromosome folding. Here the authors develop a method that makes it possible to visualize and investigate chromosome folding in individual cells at the genome scale

Automated summary

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. The authors developed the Single-Cell Chromosome Conformation Calculator (Si-C) within the Bayesian theory framework for this purpose, demonstrating its potential for visualizing and investigating interactions between all chromatin loci at the genome scale in individual cells. This method is essential in investigating chromosome folding and can reveal cell-to-cell varying domain structures and hyperfine structures in domains, such as loops.