跨物种转录组学翻译揭示了在Mycobacterium结核病感染中展开的蛋白质反应的作用
Krista M Pullen1, Ryan Finethy2, Seung-Hyun B Ko1
1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
NPJ systems biology and applications
|February 15, 2025
概括
研究人员发现,展开的蛋白质反应途径对于在小鼠模型中预测人类结核病 (TB) 是至关重要的. 这种细胞应激机制影响免疫反应,弥合了动物研究和人类疾病理解之间的差距.
科学领域:
- 免疫学 免疫学 免疫学
- 计算生物学 计算生物学
- 传染性疾病 传染性疾病
背景情况:
- 鼠标和人类结核病 (TB) 现型之间的血液转录组签名存在相似之处.
- 鼠感染病理生理学与人类结核病不同,这表明生物通路的重要性在物种之间存在差异.
研究的目的:
- 通过确定与人类结核病最相关的临床前数据变异来弥合结核病研究中的动物对人类的差距.
- 研究特定生物途径在解释结核病理生理学跨物种差异方面的作用.
主要方法:
- 应用了一个系统建模框架,可翻译组件回归,以分析临床前结核病数据.
- 从跨物种分析中确定了可预测人类结核病表型的关键生物学途径.
- 验证了已识别的途径在感染Mycobacterium结核病的小鼠巨细胞中的作用.
主要成果:
- 跨物种模型强调了感染诱导的未折叠蛋白质反应作为人类结核病表型的高度预测.
- 已证实,在M.结核病感染期间,未折叠的蛋白质反应可以调节小鼠巨细胞中的免疫功能.
- 系统级建模增强了小鼠研究的翻译价值,以了解人类结核病.
结论:
- 生物学途径相对重要性的差异有助于结核病病理生理学的跨物种变化.
- 感染诱导的未折叠蛋白质反应是理解小鼠和人类结核病的关键途径.
- 计算模型是增强动物模型在人类疾病研究中的相关性有价值的工具.
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