Quantifying the state of cell differentiation based on the gene networks entropy / 生物工程学报

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.