Summary: Quantitative tools are needed to leverage the unprecedented resolution of single-cell high-throughput chromatin conformation (scHi-C) data and integrate it with other single-cell data modalities. We present single-cell gene associating domain (scGAD) scores as a dimension reduction and exploratory analysis tool for scHi-C data. scGAD enables summarization at the gene unit while accounting for inherent gene-level genomic biases. Low-dimensional projections with scGAD capture clustering of cells based on their 3D structures. Significant chromatin interactions within and between cell types can be identified with scGAD. We further show that scGAD facilitates the integration of scHi-C data with other single-cell data modalities by enabling its projection onto reference low-dimensional embeddings. This multi-modal data integration provides an automated and refined cell-type annotation for scHi-C data.
Availability And Implementation: scGAD is part of the BandNorm R package at https://sshen82.github.io/BandNorm/articles/scGAD-tutorial.html.
Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btac372 | DOI Listing |
J Am Stat Assoc
June 2024
Department of Statistics, University of Wisconsin, Madison, WI, USA, 53706.
Emerging single cell technologies that simultaneously capture long-range interactions of genomic loci together with their DNA methylation levels are advancing our understanding of three-dimensional genome structure and its interplay with the epigenome at the single cell level. While methods to analyze data from single cell high throughput chromatin conformation capture (scHi-C) experiments are maturing, methods that can jointly analyze multiple single cell modalities with scHi-C data are lacking. Here, we introduce Muscle, a semi-nonnegative joint decomposition of Multiple single cell tensors, to jointly analyze 3D conformation and DNA methylation data at the single cell level.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
Department of Statistics, University of California Riverside, 900 University Ave., Riverside, 92521, CA, USA.
Nat Commun
September 2024
Division of Biostatistics, The Medical College of Wisconsin, Milwaukee, WI, USA.
An integration of 3D chromatin structure and gene expression at single-cell resolution has yet been demonstrated. Here, we develop a computational method, a multiomic data integration (MUDI) algorithm, which integrates scHi-C and scRNA-seq data to precisely define the 3D-regulated and biological-context dependent cell subpopulations or topologically integrated subpopulations (TISPs). We demonstrate its algorithmic utility on the publicly available and newly generated scHi-C and scRNA-seq data.
View Article and Find Full Text PDFMethods Mol Biol
September 2024
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
Single-cell Hi-C (scHi-C) is a collection of protocols for studying genomic interactions within individual cells. Although data analysis for scHi-C resembles data analysis for bulk Hi-C, the unique challenges of scHi-C, such as high noise and protocol-specific biases, require specialized data processing strategies. In this tutorial chapter, we focus on using pairtools, a suite of tools optimized for scHi-C data, demonstrating its application on a Drosophila snHi-C dataset.
View Article and Find Full Text PDFBrief Bioinform
July 2024
Department of Biostatistics, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, NC 27599, United States.
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.
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