SnapHiC-D: a computational pipeline to identify differential chromatin contacts from single-cell Hi-C data

Author:

Lee Lindsay1,Yu Miao23,Li Xiaoqi4,Zhu Chenxu256,Zhang Yanxiao27,Yu Hongyu89,Chen Ziyin3,Mishra Shreya1,Ren Bing210,Li Yun111213,Hu Ming1ORCID

Affiliation:

1. Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation , Cleveland, OH , USA

2. Ludwig Institute for Cancer Research , La Jolla, CA , USA

3. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University , Shanghai , China

4. Carolina Health Informatics Program, University of North Carolina , Chapel Hill, NC , USA

5. New York Genome Center , New York, NY , USA

6. Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medicine , New York, NY , USA

7. Westlake University , Hangzhou, Zhejiang , China

8. Department of Statistics, University of Wisconsin Madison , Madison, WI , USA

9. Department of Biochemistry, University of Wisconsin Madison , Madison, WI , USA

10. Center for Epigenomics & Department of Cellular and Molecular Medicine, University of California , San Diego, La Jolla, CA , USA

11. Department of Biostatistics, University of North Carolina , Chapel Hill, NC , USA

12. Department of Genetics, University of North Carolina , Chapel Hill, NC , USA

13. Department of Computer Science, University of North Carolina , Chapel Hill, NC , USA

Abstract

Abstract Single-cell high-throughput chromatin conformation capture technologies (scHi-C) has been used to map chromatin spatial organization in complex tissues. However, computational tools to detect differential chromatin contacts (DCCs) from scHi-C datasets in development and through disease pathogenesis are still lacking. Here, we present SnapHiC-D, a computational pipeline to identify DCCs between two scHi-C datasets. Compared to methods designed for bulk Hi-C data, SnapHiC-D detects DCCs with high sensitivity and accuracy. We used SnapHiC-D to identify cell-type-specific chromatin contacts at 10 Kb resolution in mouse hippocampal and human prefrontal cortical tissues, demonstrating that DCCs detected in the hippocampal and cortical cell types are generally associated with cell-type-specific gene expression patterns and epigenomic features. SnapHiC-D is freely available at https://github.com/HuMingLab/SnapHiC-D.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Information Systems

Reference66 articles.

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