在类风湿性关节炎中空间转录组学的深度主题建模确定了不同类型的宫外淋巴体结构
Preethi K Periyakoil1,2, Melanie H Smith2,3, Meghana Kshirsagar4
1Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
bioRxiv : the preprint server for biology
|January 20, 2025
概括
空间转录学揭示了类风湿性关节炎中不同的微环境. 深度话题在异位淋巴体结构中确定了独特的细胞社区和不同的架构,为疾病机制提供了洞察力.
科学领域:
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
- 计算生物学 计算生物学
背景情况:
- 类风湿性关节炎 (RA) 的协同细胞表现出显著的细胞异质性.
- 在RA中,了解细胞与细胞之间的相互作用和微环境影响至关重要.
- 以前的单细胞RNA测序研究强调了细胞状态的多样性,但缺乏空间背景.
研究的目的:
- 通过空间转录学 (ST) 在RA同胞体内定义稳定的微环境.
- 为了表征RA中异位淋巴体结构 (ELS) 的细胞组成.
- 开发一种新的计算方法,从ST数据中识别疾病相关的细胞群体.
主要方法:
- 应用空间转录学 (ST) 对六名RA患者的八个突组织样本.
- 开发了DeepTopics,这是一个可扩展的,无引用的解卷方法,使用迪里克莱特变量自编码器.
- 分析了22个代表不同细胞群体和生物过程的已识别主题.
主要成果:
- DeepTopics确定了22个不同的主题,其特点是特定的细胞类型,激活状态和生物过程.
- 观察到细胞类型的同位化,如CD34纤维细胞和LYVE1巨细胞,表明功能相互作用.
- 在ELS中发现了两种不同的,稳定的细胞模式,以"生殖中心类似"主题的存在或不存在来区分.
结论:
- DeepTopics是一个有效的方法,用于从ST数据中识别与疾病相关的微环境.
- 具有相似组织结构的RA突样本可以表现出不同的细胞结构.
- 这些发现对理解类风湿性关节炎的发病因子有重大意义.
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