通过综合生物信息学识别皮肤肌炎和类风湿性关节炎之间的共同基因和生物标志物
Fo Yang1, Qishui Xia1, Mingjun Wu1
1Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, China.
PloS one
|February 4, 2026
概括
这项研究揭示了共享的分子通路,包括IL-17和化学激素信号传递,在类风湿性关节炎 (RA) 和皮肤肌炎 (DM). HCP5和RARRES3被确定为这些相关的自身免疫性疾病的潜在生物标志物.
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:
- 皮质神经炎 (DM) 和类风湿性关节炎 (RA) 具有共同的炎症特征,但它们共同疾病的潜在分子机制尚未完全理解.
- 调查共享的分子通路对于了解这些相关的自身免疫性疾病的病原体至关重要.
研究的目的:
- 在DM和RA中识别共享的分子机制和免疫微环境变化,使用集成的多omics和机器学习.
- 发现DM和RA并发症的潜在诊断生物标志物.
主要方法:
- 针对RA和DM的微阵列数据集的综合分析,包括差异基因表达 (DEG) 分析和加权基因共同表达网络分析 (WGCNA).
- 使用LASSO回归和随机森林建模来优先考虑核心基因,然后在外部队列中进行验证.
- 使用CIBERSORT和单样样本基因组丰富分析 (ssGSEA) 进行免疫景观和细胞亚种群概况.
- 单细胞RNA测序 (scRNA-seq) 用于绘制细胞类型特定的基因表达和推断连接体-受体相互作用.
主要成果:
- 在RA和DM中确定了IL-17,托尔类受体 (TLR) 和化学激素信号传导的丰富的共享通路.
- 优先考虑了四个核心基因 (JUNB,NRGN,HCP5,RARRES3),其中HCP5和RARRES3在外部数据集中显示出显著的差异表达和诊断潜力.
- 揭示了免疫微环境的改变,包括激活的CD4+记忆T细胞和M2极化巨细胞的丰富,以及核心基因和免疫细胞状态之间的动态关联.
- scRNA-seq局部化了核心基因表达到NK细胞,单细胞和T / B细胞等免疫细胞,突出了炎症性联体受体相互作用.
结论:
- 整合性,机器学习辅助的转录学确定了聚合的RA-DM分子程序,以IL-17,TLR和化学因路径为中心.
- HCP5和RARRES3成为具有诊断潜力的可复制候选生物标志物,与巨细胞极化和T细胞状态有关.
- 这些发现提名可测试的生物标志物和可验证的途径,为RA-DM并发症的跨疾病治疗策略提供了理由.
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