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基于单细胞 RNA 测序数据构建的细胞特异性网络。

Cell-specific network constructed by single-cell RNA sequencing data.

机构信息

Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.

Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China.

出版信息

Nucleic Acids Res. 2019 Jun 20;47(11):e62. doi: 10.1093/nar/gkz172.

Abstract

Single-cell RNA sequencing (scRNA-seq) is able to give an insight into the gene-gene associations or transcriptional networks among cell populations based on the sequencing of a large number of cells. However, traditional network methods are limited to the grouped cells instead of each single cell, and thus the heterogeneity of single cells will be erased. We present a new method to construct a cell-specific network (CSN) for each single cell from scRNA-seq data (i.e. one network for one cell), which transforms the data from 'unstable' gene expression form to 'stable' gene association form on a single-cell basis. In particular, it is for the first time that we can identify the gene associations/network at a single-cell resolution level. By CSN method, scRNA-seq data can be analyzed for clustering and pseudo-trajectory from network perspective by any existing method, which opens a new way to scRNA-seq data analyses. In addition, CSN is able to find differential gene associations for each single cell, and even 'dark' genes that play important roles at the network level but are generally ignored by traditional differential gene expression analyses. In addition, CSN can be applied to construct individual network of each sample bulk RNA-seq data. Experiments on various scRNA-seq datasets validated the effectiveness of CSN in terms of accuracy and robustness.

摘要

单细胞 RNA 测序 (scRNA-seq) 能够通过对大量细胞进行测序,深入了解细胞群体之间的基因-基因关联或转录网络。然而,传统的网络方法仅限于分组细胞,而不是每个单细胞,因此单细胞的异质性将被抹去。我们提出了一种从 scRNA-seq 数据为每个单细胞构建细胞特异性网络 (CSN) 的新方法(即一个细胞一个网络),它将数据从“不稳定”的基因表达形式转换为单细胞基础上的“稳定”基因关联形式。特别是,我们首次可以在单细胞分辨率水平上识别基因关联/网络。通过 CSN 方法,可以从网络角度对 scRNA-seq 数据进行聚类和拟轨迹分析,为 scRNA-seq 数据分析开辟了新途径。此外,CSN 能够为每个单细胞找到差异基因关联,甚至是在网络水平上发挥重要作用但通常被传统差异基因表达分析忽略的“暗”基因。此外,CSN 可应用于构建每个样本批量 RNA-seq 数据的个体网络。在各种 scRNA-seq 数据集上的实验验证了 CSN 在准确性和稳健性方面的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdb3/6582408/48c7df34a449/gkz172fig1.jpg

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