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

Area of Science:

• Genomics
• Computational Biology
• Epigenetics

Background:

• Single-cell Hi-C (scHi-C) enables measurement of spatial proximity between regulatory elements and target genes.
• Identifying long-range enhancer-promoter interactions is crucial for understanding gene regulation.
• Existing methods may lack sensitivity or specificity in complex cellular environments.

Purpose of the Study:

• To develop a computational method, SnapHiC-G, for identifying long-range enhancer-promoter interactions from scHi-C data.
• To apply SnapHiC-G to diverse cell types, including mouse embryonic stem cells and human brain cortical cells.
• To assess the utility of SnapHiC-G in linking noncoding genetic variants to disease heritability.

Main Methods:

• Development of SnapHiC-G, a computational approach utilizing a global background model.
• Application of SnapHiC-G to analyze scHi-C datasets from mouse embryonic stem cells and human brain cortical cells.
• Evaluation of SnapHiC-G's sensitivity and specificity in detecting enhancer-promoter interactions.

Main Results:

• SnapHiC-G demonstrated high sensitivity in identifying long-range enhancer-promoter interactions.
• The method successfully identified putative target genes for noncoding genome-wide association study (GWAS) variants.
• Genetic heritability of neuropsychiatric diseases was found to be enriched in SNPs within SnapHiC-G-identified interactions in a cell-type-specific manner.

Conclusions:

• SnapHiC-G is a powerful computational tool for characterizing cell-type-specific enhancer-promoter interactions.
• The method facilitates the discovery of chromatin interactions critical for gene regulation in complex tissues.
• SnapHiC-G aids in understanding the genetic basis of diseases by linking variants to specific regulatory elements.