通过生物信息学分析和机器学习算法识别和验证活跃结核病中NET相关的生物标志物
Shengfang Xia1, Qi An1, Rui Lin1
1Department of Science and Education Division, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, China.
Frontiers in immunology
|July 3, 2025
概括
这项研究确定了与中性细胞外细胞陷 (NETs) 相关的基因 (CD274,IRF1,HPSE) 作为早期活性结核病 (ATB) 检测的潜在生物标志物,有助于区分ATB与潜在结核病感染 (LTBI). 这些发现为结核病诊断和治疗提供了新的途径.
科学领域:
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
- 医学诊断 医学诊断 医学诊断
背景情况:
- 结核病 (TB) 的诊断延迟阻碍了全球控制工作.
- 中性细胞外细胞陷 (NETs) 在结核病免疫病理学中发挥作用.
- 需要生物标志物来区分活跃结核病 (ATB) 和潜伏结核病感染 (LTBI).
研究的目的:
- 探索与NETs相关的生物标志物,以区分ATB和LTBI.
- 确定关键的基因和参与NETs介导的结核病理学的调节网络.
- 预测结核病治疗的潜在药物改用候选人.
主要方法:
- 使用微分表达式分析分析转录组数据集的分析.
- 免疫细胞分析和机器学习算法 (SVM-RFE,LASSO,随机森林).
- 监管相互作用和药物标预测的网络分析.
主要成果:
- 三个枢纽基因 (CD274,IRF1,HPSE) 显示了ATB的高诊断准确性 (AUC为0.865-0.98).
- IRF1和HPSE与中性粒细胞透相关,表明参与NETosis.
- 确定了核心调节剂 (FOXC1,GATA2,hsa-miR-106a-5p) 和46种潜在的候选药物.
结论:
- CD274,IRF1和HPSE是ATB诊断的NETs衍生的有希望的生物标志物.
- 这些基因对中性粒细胞介导免疫具有潜在的治疗意义.
- 需要进一步的临床前验证来重新定位药物; 建议进行机械学研究.
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