With the dramatic development of single-cell RNA sequencing (scRNA-seq) technologies, the systematic decoding of cell-cell communication has received great research interest. To date, several in-silico methods have been developed, but most of them lack the ability to predict the communication pathways connecting the insides and outsides of cells. Here, we developed CellCall, a toolkit to infer inter- and intracellular communication pathways by integrating paired ligand-receptor and transcription factor (TF) activity. Moreover, CellCall uses an embedded pathway activity analysis method to identify the significantly activated pathways involved in intercellular crosstalk between certain cell types. Additionally, CellCall offers a rich suite of visualization options (Circos plot, Sankey plot, bubble plot, ridge plot, etc.) to present the analysis results. Case studies on scRNA-seq datasets of human testicular cells and the tumor immune microenvironment demonstrated the reliable and unique functionality of CellCall in intercellular communication analysis and internal TF activity exploration, which were further validated experimentally. Comparative analysis of CellCall and other tools indicated that CellCall was more accurate and offered more functions. In summary, CellCall provides a sophisticated and practical tool allowing researchers to decipher intercellular communication and related internal regulatory signals based on scRNA-seq data. CellCall is freely available at https://github.com/ShellyCoder/cellcall.

中文翻译：

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CellCall：整合配对配体-受体和转录因子活性以进行细胞间通讯

随着单细胞RNA测序（scRNA-seq）技术的飞速发展，细胞间通讯的系统解码引起了极大的研究兴趣。迄今为止，已经开发了几种计算机方法，但其中大多数缺乏预测连接细胞内部和外部的通信途径的能力。在这里，我们开发了 CellCall，这是一个通过整合配对配体受体和转录因子 (TF) 活性来推断细胞间和细胞内通讯途径的工具包。此外，CellCall 使用嵌入式通路活性分析方法来识别参与某些细胞类型之间的细胞间串扰的显着激活的通路。此外，CellCall 还提供了丰富的可视化选项（Circos 图、Sankey 图、气泡图、岭图等）来呈现分析结果。对人类睾丸细胞和肿瘤免疫微环境的 scRNA-seq 数据集的案例研究证明了 CellCall 在细胞间通讯分析和内部 TF 活性探索方面可靠且独特的功能，并得到了实验的进一步验证。CellCall与其他工具的对比分析表明，CellCall的准确性更高，功能更多。总之，CellCall 提供了一种复杂而实用的工具，使研究人员能够根据 scRNA-seq 数据破译细胞间通讯和相关的内部调节信号。CellCall 可在 https://github.com/ShellyCoder/cellcall 上免费获取。