Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity

Longqi Liu, Chuanyu Liu, Andrés Quintero, Liang Wu, Yue Yuan, Mingyue Wang, Mengnan Cheng, Lizhi Leng, Liqin Xu, Guoyi Dong, Rui Li, Yang Liu, Xiaoyu Wei, Jiangshan Xu, Xiaowei Chen, Haorong Lu, Dongsheng Chen, Quanlei Wang, Qing Zhou, Xinxin Lin, Guibo Li, Shiping Liu, Qi Wang, Hongru Wang, J. Lynn Fink, Zhengliang Gao, Xin Liu, Yong Hou, Shida Zhu, Huanming Yang, Yunming Ye, Ge Lin, Fang Chen, Carl Herrmann, Roland Eils (), Zhouchun Shang () and Xun Xu ()
Additional contact information
Longqi Liu: BGI-Shenzhen
Chuanyu Liu: BGI-Shenzhen
Andrés Quintero: German Cancer Research Center (DKFZ)
Liang Wu: BGI-Shenzhen
Yue Yuan: BGI-Shenzhen
Mingyue Wang: BGI-Shenzhen
Mengnan Cheng: BGI-Shenzhen
Lizhi Leng: Central South University
Liqin Xu: BGI-Shenzhen
Guoyi Dong: BGI-Shenzhen
Rui Li: BGI-Shenzhen
Yang Liu: BGI-Shenzhen
Xiaoyu Wei: BGI-Shenzhen
Jiangshan Xu: BGI-Shenzhen
Xiaowei Chen: China National GeneBank, BGI-Shenzhen
Haorong Lu: China National GeneBank, BGI-Shenzhen
Dongsheng Chen: BGI-Shenzhen
Quanlei Wang: BGI-Shenzhen
Qing Zhou: BGI-Shenzhen
Xinxin Lin: BGI-Shenzhen
Guibo Li: BGI-Shenzhen
Shiping Liu: BGI-Shenzhen
Qi Wang: German Cancer Research Center (DKFZ)
Hongru Wang: Chinese Academy of Sciences
J. Lynn Fink: BGI-Shenzhen
Zhengliang Gao: Tongji University School of Medicine
Xin Liu: BGI-Shenzhen
Yong Hou: BGI-Shenzhen
Shida Zhu: BGI-Shenzhen
Huanming Yang: BGI-Shenzhen
Yunming Ye: Xili University Town
Ge Lin: Central South University
Fang Chen: BGI-Shenzhen
Carl Herrmann: German Cancer Research Center (DKFZ)
Roland Eils: Heidelberg University Hospital
Zhouchun Shang: BGI-Shenzhen
Xun Xu: BGI-Shenzhen

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-08205-7

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