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

Author:

Liu Weifang1ORCID,Zhong Wujuan2,Giusti-Rodríguez Paola3,Jiang Zhiyun4,Wang Geoffery W1,Sun Huaigu4,Hu Ming56ORCID,Li Yun147ORCID

Affiliation:

1. Department of Biostatistics, University of North Carolina at Chapel Hill , 135 Dauer Drive, Chapel Hill, NC 27599, United States

2. Biostatistics and Research Decision Sciences, Merck & Co., Inc. , 126 East Lincoln Ave, Rahway, New Jersey 07065, United States

3. Department of Psychiatry, University of Florida , 1149 Newel Dr., Gainesville, FL 32611, United States

4. Department of Genetics, University of North Carolina at Chapel Hill , 120 Mason Farm Road, Chapel Hill, NC 27599, United States

5. Department of Quantitative Health Sciences , Lerner Research Institute, , 9500 Euclid Avenue, Cleveland, OH 44196, United States

6. Cleveland Clinic Foundation , Lerner Research Institute, , 9500 Euclid Avenue, Cleveland, OH 44196, United States

7. Department of Computer Science, University of North Carolina at Chapel Hill , 201 S. Columbia St, Chapel Hill, NC 27599, United States

Abstract

Abstract 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. SnapHiC-G achieved high sensitivity in identifying long-range enhancer–promoter interactions. Moreover, SnapHiC-G can identify putative target genes for noncoding genome-wide association study (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.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

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