Si-C: method to infer biologically valid super-resolution intact genome structure from single-cell Hi-C data

Abstract

There is a strong demand for the methods that can efficiently reconstruct biologically valid super-resolution intact genome 3D structures from sparse and noise single-cell Hi-C data. Here, we developed Single-Cell Chromosome Conformation Calculator (Si-C) within the Bayesian theory framework and applied this approach to reconstruct intact genome 3D structures from the 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 revealed 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 demonstrates the potential for visualizing and investigating interactions between all chromatin loci at genome scale in individual cells.