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[基于基因网络熵量化细胞分化状态]

[Quantifying the state of cell differentiation based on the gene networks entropy].

作者信息

Guan Tianhao, Gao Jie

机构信息

School of Sciences, Jiangnan University, Wuxi 214122, Jiangsu, China.

出版信息

Sheng Wu Gong Cheng Xue Bao. 2022 Feb 25;38(2):820-830. doi: 10.13345/j.cjb.210140.

Abstract

Studies of cellular dynamic processes have shown that cells undergo state changes during dynamic processes, controlled mainly by the expression of genes within the cell. With the development of high-throughput sequencing technologies, the availability of large amounts of gene expression data enables the acquisition of true gene expression information of cells at the single-cell level. However, most existing research methods require the use of information beyond gene expression, thus introducing additional complexity and uncertainty. In addition, the prevalence of dropout events hampers the study of cellular dynamics. To this end, we propose an approach named gene interaction network entropy (GINE) to quantify the state of cell differentiation as a means of studying cellular dynamics. Specifically, by constructing a cell-specific network based on the association between genes through the stability of the network, and defining the GINE, the unstable gene expression data is converted into a relatively stable GINE. This method has no additional complexity or uncertainty, and at the same time circumvents the effects of dropout events to a certain extent, allowing for a more reliable characterization of biological processes such as cell fate. This method was applied to study two single-cell RNA-seq datasets, head and neck squamous cell carcinoma and chronic myeloid leukaemia. The GINE method not only effectively distinguishes malignant cells from benign cells and differentiates between different periods of differentiation, but also effectively reflects the disease efficacy process, demonstrating the potential of using GINE to study cellular dynamics. The method aims to explore the dynamic information at the level of single cell disorganization and thus to study the dynamics of biological system processes. The results of this study may provide scientific recommendations for research on cell differentiation, tracking cancer development, and the process of disease response to drugs.

摘要

细胞动态过程的研究表明,细胞在动态过程中会发生状态变化,主要受细胞内基因表达的控制。随着高通量测序技术的发展,大量基因表达数据的可得性使得在单细胞水平上获取细胞真实的基因表达信息成为可能。然而,大多数现有的研究方法需要使用基因表达之外的信息,从而引入了额外的复杂性和不确定性。此外,缺失事件的普遍存在阻碍了细胞动力学的研究。为此,我们提出了一种名为基因相互作用网络熵(GINE)的方法,以量化细胞分化状态,作为研究细胞动力学的一种手段。具体而言,通过基于基因之间的关联构建细胞特异性网络,并通过网络的稳定性定义GINE,将不稳定的基因表达数据转化为相对稳定的GINE。该方法没有额外的复杂性或不确定性,同时在一定程度上规避了缺失事件的影响,能够更可靠地表征细胞命运等生物学过程。该方法被应用于研究两个单细胞RNA测序数据集,即头颈部鳞状细胞癌和慢性髓性白血病。GINE方法不仅能有效区分恶性细胞和良性细胞,并区分不同的分化时期,还能有效反映疾病疗效过程,证明了使用GINE研究细胞动力学的潜力。该方法旨在探索单细胞无序水平的动态信息,从而研究生物系统过程的动力学。本研究结果可能为细胞分化、追踪癌症发展以及疾病对药物反应过程的研究提供科学建议。

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