展开的蛋白质反应途径是COVID-19和败血症病变的可能联系
Hong Liu1, Junyi Wang2, Shaofeng Li3
1School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Archives of virology
|January 9, 2024
概括
COVID-19和败血症共享一种共同的致病机制,涉及B细胞和展开的蛋白质反应 (UPR) 途径. 这项研究开发了一种高度准确的机器学习模型来识别这种共享路径.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 计算生物学 计算生物学
背景情况:
- "COVID-19"疫情凸显了其全球重大影响.
- 临床证据表明,COVID-19和败血症之间存在很强的联系.
- 展开的蛋白质反应 (UPR) 途径与这两种疾病有关,但尚未证实一种共同的机制.
研究的目的:
- 为了调查UPR途径是否作为COVID-19和败血症的常见致病机制.
- 为了确定关键的细胞子集和信号通路涉及到两个条件.
- 根据这些发现,开发和验证基于机器学习的诊断模型.
主要方法:
- 通过Gene Expression Omnibus (GEO) 下载和分析了来自COVID-19和败血症病例的单细胞RNA测序 (scRNA-seq) 和转录组数据.
- 确定了B细胞作为关键细胞子集和UPR通路作为关键信号通路.
- 使用与B细胞和UPR通路相关的交联基因构建了一个机器学习诊断模型.
主要成果:
- 单细胞转录组分析确定了B细胞和UPR通路作为COVID-19和败血症病原体的核心.
- 开发的机器学习模型在内部和外部验证数据集中显示出高准确性和稳定性.
- 将模型与临床数据集成并没有改变其诊断性能,证实了其稳定性.
结论:
- COVID-19和败血症可能在单细胞水平上具有共同的分子致病机制,以B细胞和UPR途径为中心.
- 这项研究为这两个关键条件的病变产生提供了新的分子视角.
- 经过验证的机器学习模型显示了可靠诊断和理解共享疾病机制的潜力.
相关概念视频
The Unfolded Protein Response
4.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.6K
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Role of ER in the Secretory Pathway
5.4K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.4K
NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K
The Proteasome
845
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
845
The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K


