scdNet: a computational tool for single-cell differential network analysis

scdNet: a computational tool for single-cell differential network analysis
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DOI:
10.1186/s12918-018-0652-0
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发表时间:
2018-12-21
影响因子:
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通讯作者:
Shao, Yu-Hsuan Joni
Shao, Yu-Hsuan Joni
中科院分区:
生物2区
文献类型:
--
作者:
Chiu, Yu-Chiao;Hsiao, Tzu-Hung;Shao, Yu-Hsuan Joni

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研究背景单细胞RNA测序(single-cell RNA sequencing,scRNA-Seq)是一种新兴的技术,它对肿瘤异质性的研究产生了革命性的影响。然而,高度稀疏的数据矩阵所产生的技术差异基因调控networks.ResultsAddressing的挑战,这项研究提出了,据我们所知,第一个生物信息学工具scRNA-Seq为基础的差分网络分析(scdNet)的分析构成了障碍。该工具具有基因-基因相关性的样本量调整,状态间相关性的比较以及差分网络的构建。仿真分析表明scdNet在稀疏scRNA-Seq数据矩阵分析中的强大功能,对样本量要求低,计算效率高,并且可以容忍测序噪声。应用该工具分析两个数据集的单循环肿瘤细胞(CTC)的前列腺癌和早期小鼠胚胎,我们的数据表明,差异基因调控在抗雄激素抵抗和早期胚胎development.ConclusionsOverall中起着至关重要的作用,该工具是广泛适用于数据集所产生的新兴技术,使生物学的见解肿瘤异质性和其他研究。scdNet的MATLAB实现可在https://github.com/ChenLabGCCRI/scdNet上获得。
BackgroundSingle-cell RNA sequencing (scRNA-Seq) is an emerging technology that has revolutionized the research of the tumor heterogeneity. However, the highly sparse data matrices generated by the technology have posed an obstacle to the analysis of differential gene regulatory networks.ResultsAddressing the challenges, this study presents, as far as we know, the first bioinformatics tool for scRNA-Seq-based differential network analysis (scdNet). The tool features a sample size adjustment of gene-gene correlation, comparison of inter-state correlations, and construction of differential networks. A simulation analysis demonstrated the power of scdNet in the analyses of sparse scRNA-Seq data matrices, with low requirement on the sample size, high computation efficiency, and tolerance of sequencing noises. Applying the tool to analyze two datasets of single circulating tumor cells (CTCs) of prostate cancer and early mouse embryos, our data demonstrated that differential gene regulation plays crucial roles in anti-androgen resistance and early embryonic development.ConclusionsOverall, the tool is widely applicable to datasets generated by the emerging technology to bring biological insights into tumor heterogeneity and other studies. MATLAB implementation of scdNet is available at https://github.com/ChenLabGCCRI/scdNet.