SnapHiC-G: identifying long-range enhancer-promoter interactions from single-cell Hi-C data via a global background model

Harnessing the power of single-cell genomics technologies, single-cell Hi-C (scHi-C) and its derived technologies provide powerful tools to measure spatial proximity between regulatory elements and their target genes in individual cells. Using a global background model, we propose SnapHiC-G, a computational method to identify long-range enhancer-promoter interactions from scHi-C data. We applied SnapHiC-G to scHi-C datasets generated from mouse embryonic stem cells and human brain cortical cells and demonstrated that SnapHiC-G achieved high sensitivity in identifying long-range enhancer-promoter interactions. Moreover, SnapHiC-G can identify putative target genes for non-coding GWAS variants, and the genetic heritability of neuropsychiatric diseases is enriched for single nucleotide polymorphisms (SNPs) within SnapHiC-G-identified interactions in a cell-type-specific manner. In sum, SnapHiC-G is a powerful tool for characterizing cell-type-specific enhancer-promoter interactions from complex tissues and can facilitate the discovery of chromatin interactions important for gene regulation in biologically relevant cell types. ### Competing Interest Statement Author W.Z. was employed by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.