Dataset Information

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

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.

SUBMITTER: Liu L

PROVIDER: S-EPMC6349937 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Liu Longqi L Liu Chuanyu C Quintero Andrés A Wu Liang L Yuan Yue Y Wang Mingyue M Cheng Mengnan M Leng Lizhi L Xu Liqin L Dong Guoyi G Li Rui R Liu Yang Y Wei Xiaoyu X Xu Jiangshan J Chen Xiaowei X Lu Haorong H Chen Dongsheng D Wang Quanlei Q Zhou Qing Q Lin Xinxin X Li Guibo G Liu Shiping S Wang Qi Q Wang Hongru H Fink J Lynn JL Gao Zhengliang Z Liu Xin X Hou Yong Y Zhu Shida S Yang Huanming H Ye Yunming Y Lin Ge G Chen Fang F Herrmann Carl C Eils Roland R Shang Zhouchun Z Xu Xun X

Nature communications 20190128 1

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 ne ...[more]

PMID: 30692544

Similar Datasets

Project description:BackgroundHigh throughput single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for exploring cellular heterogeneity among complex human cancers. scRNA-Seq studies using fresh human surgical tissue are logistically difficult, preclude histopathological triage of samples, and limit the ability to perform batch processing. This hindrance can often introduce technical biases when integrating patient datasets and increase experimental costs. Although tissue preservation methods have been previously explored to address such issues, it is yet to be examined on complex human tissues, such as solid cancers and on high throughput scRNA-Seq platforms.MethodsUsing the Chromium 10X platform, we sequenced a total of ~ 120,000 cells from fresh and cryopreserved replicates across three primary breast cancers, two primary prostate cancers and a cutaneous melanoma. We performed detailed analyses between cells from each condition to assess the effects of cryopreservation on cellular heterogeneity, cell quality, clustering and the identification of gene ontologies. In addition, we performed single-cell immunophenotyping using CITE-Seq on a single breast cancer sample cryopreserved as solid tissue fragments.ResultsTumour heterogeneity identified from fresh tissues was largely conserved in cryopreserved replicates. We show that sequencing of single cells prepared from cryopreserved tissue fragments or from cryopreserved cell suspensions is comparable to sequenced cells prepared from fresh tissue, with cryopreserved cell suspensions displaying higher correlations with fresh tissue in gene expression. We showed that cryopreservation had minimal impacts on the results of downstream analyses such as biological pathway enrichment. For some tumours, cryopreservation modestly increased cell stress signatures compared to freshly analysed tissue. Further, we demonstrate the advantage of cryopreserving whole-cells for detecting cell-surface proteins using CITE-Seq, which is impossible using other preservation methods such as single nuclei-sequencing.ConclusionsWe show that the viable cryopreservation of human cancers provides high-quality single-cells for multi-omics analysis. Our study guides new experimental designs for tissue biobanking for future clinical single-cell RNA sequencing studies.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets