Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity
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Abstract
Integrative analysis of multi-omics layers at single cell level is critical for accurate dissection of cell-to-cell variation within certain cell populations. Here we report scCAT-seq, a technique for simultaneously assaying chromatin accessibility and the transcriptome within the same single cell. We show that the combined single cell signatures enable accurate construction of regulatory relationships between cis -regulatory elements and the target genes at single-cell resolution, providing a new dimension of features that helps direct discovery of regulatory patterns specific to distinct cell identities. Moreover, we generate the first single cell integrated map of chromatin accessibility and transcriptome in early embryos and demonstrate the robustness of scCAT-seq in the precise dissection of master transcription factors in cells of distinct states. The ability to obtain these two layers of omics data will help provide more accurate definitions of “single cell state” and enable the deconvolution of regulatory heterogeneity from complex cell populations.
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Correlation-based methods are used to link peaks to genes within clusters to identify potential CREs.
“To identify potential CREs, correlation-based methods are used to link peaks to genes within clusters of cells140,143,156.”
From Best practices for single-cell analysis across modalities (2023) · cites this paper as [156]
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- Authors
- Liu, L., Liu, C., Quintero, A., Wu, L., Yuan, Y., Wang, M., Cheng, M., Leng, L., Xu, L., Dong, G., Li, R., Liu, Y., Wei, X., Xu, J., Chen, X., Lu, H., Chen, D., Wang, Q., Zhou, Q., Lin, X., Li, G., Liu, S., Wang, Q., Wang, H., Fink, J. L., Gao, Z., Liu, X., Hou, Y., Zhu, S., Yang, H., Ye, Y., Lin, G., Chen, F., Herrmann, C., Eils, R., Shang, Z., & Xu, X.
- Affiliations
- BGI Group (China) (CN)
- German Cancer Research Center (DE)
- Central South University (CN)
- China National GeneBank (CN)
- Chinese Academy of Sciences (CN)
- Tongji University (CN)
- Harbin Institute of Technology (CN)
- University Hospital Heidelberg (DE)
- Corresponding author
- Eils, Roland
- Shang, Zhouchun
- Xu, Xun
- ORCID
- Liu, Longqi
- Liu, Chuanyu
- Quintero, Andrés
- Wu, Liang
- Yuan, Yue
- Wang, Mingyue
- Xu, Liqin
- Dong, Guoyi
- Li, Rui
- Liu, Yang
- Wei, Xiaoyu
- Xu, Jiangshan
- Chen, Xiaowei
- Lu, Haorong
- Chen, Dongsheng
- Wang, Quanlei
- Zhou, Qing
- Lin, Xinxin
- Li, Guibo
- Liu, Shiping
- Wang, Qi
- Wang, Hongru
- Fink, J. Lynn
- Gao, Zhengliang
- Liu, Xin
- Hou, Yong
- Zhu, Shida
- Yang, Huanming
- Lin, Ge
- Herrmann, Carl
- Eils, Roland
- Shang, Zhouchun
- Xu, Xun
- Venue
- Nature Communications
- Published
- 2019-01-28
- Volume
- 10
- Issue
- 1
- Pages
- 470-470
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6349937
- OpenAlex
- W2951343553
- Cited by
- 243
- References
- 45
- Citations by year
- 2026: 16 · 2025: 35 · 2024: 37 · 2023: 42 · 2022: 33 · 2021: 35 · 2020: 31 · 2019: 13 · 2018: 1
- FWCI
- 9.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- Chinese Academy of Sciences
- China Postdoctoral Science Foundation
- Government of Jiangxi Province
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- single-cell multi-omics, chromatin accessibility, transcriptome, cis-regulatory elements, gene expression regulation, regulatory heterogeneity, cell-to-cell variability, early embryo, master transcription factors, integrative analysis
- MeSH terms
- Chromatin, Embryo, Mammalian, Gene Expression Regulation, HeLa Cells, Humans, Regulatory Sequences, Nucleic Acid, Sequence Analysis, DNA, K562 Cells, HCT116 Cells, Epigenomics, Single-Cell Analysis, Transcriptome
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