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SCANCell 揭示了系统性红斑狼疮在疾病谱中不同簇间的相互作用模式。

SCANCell reveals diverse inter-cluster interaction patterns in systemic lupus erythematosus across the disease spectrum.

机构信息

State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.

Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200030, China.

出版信息

Bioinformatics. 2022 Feb 7;38(5):1361-1368. doi: 10.1093/bioinformatics/btab713.

Abstract

MOTIVATION

High-dimensional mass cytometry (CyTOF), which provides both cellular signatures and inter-cluster interactions like the antagonism between immune activation and suppression, and the pro-inflammatory synergy, sheds light on the cellular and molecular basis of disease pathogenesis. However, revealing the aberrance of inter-cluster communication networks in CyTOF datasets remains a significant challenge.

RESULTS

Here, we developed Sample Classification and direct Association Network among Cell clusters (SCANCell) that quantifies the direct association (DA) network of cell clusters. SCANCell was applied to profile inter-cluster interaction patterns of a well-recruited systemic lupus erythematosus (SLE) cohort, including 8 healthy controls, 10 active SLE patients (APs) and 8 remission SLE patients (RPs). SCANCell identified decreased inter-cluster interactions of CD8+ T cells in APs compared with RPs, and enhanced DA of CD8+ T cells after stimulation with immunostimulatory cytokine interleukin-2 in vitro. These discoveries prove that SCANCell can uncover pathology- and drug stimulation-associated inter-cluster interactions, which potentially benefits understanding of pathogenesis and novel therapeutic strategies.

AVAILABILITY AND IMPLEMENTATION

The main processing scripts of SCNACell are available at https://github.com/Lxc417/SCANCell. Other codes for the following data statistics are available from the corresponding author upon request.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

高维液质流式细胞术(CyTOF)既能提供细胞特征,又能提供簇间相互作用,如免疫激活与抑制之间的拮抗作用,以及促炎协同作用,为疾病发病机制的细胞和分子基础提供了线索。然而,揭示 CyTOF 数据集中簇间通讯网络的失常仍然是一个重大挑战。

结果

在这里,我们开发了样本分类和细胞簇间直接关联网络(SCANCell),该方法可量化细胞簇的直接关联(DA)网络。SCANCell 用于对招募良好的系统性红斑狼疮(SLE)队列的簇间相互作用模式进行分析,该队列包括 8 名健康对照、10 名活动期 SLE 患者(APs)和 8 名缓解期 SLE 患者(RPs)。SCANCell 发现与 RPs 相比,APs 中 CD8+T 细胞的簇间相互作用减少,并且体外用免疫刺激细胞因子白细胞介素-2 刺激后 CD8+T 细胞的 DA 增强。这些发现证明了 SCANCell 可以揭示与病理学和药物刺激相关的簇间相互作用,这可能有助于理解发病机制和新的治疗策略。

可用性和实施

SCANCell 的主要处理脚本可在 https://github.com/Lxc417/SCANCell 上获得。如需其他数据统计代码,请向相应作者索取。

补充信息

补充数据可在生物信息学在线获得。

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