大量微阵列和单细胞转录组分析揭示了毒症中与细菌脂多糖相关的生物标志物
Haili Zhang1, Xiaoying Wu1, Lixue Wu1
1Department of Emergency Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Drug development research
|February 6, 2026
概括
研究人员确定了关键的脂聚糖类 (LPS) 相关基因,用于败血症诊断和预后. 这种LPS生物标志物模型整合了批量和单细胞数据,为败血症管理提供了新的见解.
科学领域:
- 生物化学和分子生物学
- 免疫学 免疫学 免疫学
- 计算生物学 计算生物学
背景情况:
- 败血症是一种危及生命的器官功能障碍,是由宿主对感染反应失调引起的.
- 确定可靠的败血症生物标志物,特别是与脂聚糖 (LPS) 相关的生物标志物,对于有效的诊断和治疗至关重要.
- 目前对败血症中LPS相关机制的理解需要进一步探索.
研究的目的:
- 识别和验证与败血症相关的脂多糖 (LPS) 相关基因 (LRG).
- 开发和评估使用集成的转录基因数据用于败血症的诊断和预后生物标志物模型.
- 为了阐明细胞类型特定的LRG表达和细胞间通信网络在败血症.
主要方法:
- 集成的批量微阵列和单细胞RNA测序 (scRNA-seq) 数据集来自基因表达大盘.
- 应用了细胞聚类,注释,AUCell评分和细胞-细胞通信分析,使用scRNA-seq.
- 利用机器学习算法 (LASSO,SVM-RFE,XGBoost) 进行生物标志物选择和通过qRT-PCR验证基因表达.
主要成果:
- 确定了七个关键的LPS相关基因 (LRGs),与败血症密切相关.
- 在独立验证队列中开发了具有高精度 (AUC > 0.89) 的诊断和预后模型.
- 在高风险败血症患者中观察到骨髓原抑制细胞和巨细胞透的增加,激活的炎症通路和独特的通信网络.
结论:
- 建立了一个经过验证的LPS相关生物标志物模型,集成大量和单细胞转录组学来治疗败血症.
- 该模型显示了毒症诊断和预后的重大潜力.
- 这些发现为败血症的发病和潜在的治疗点提供了新的见解,特别是在髓状细胞群中.
相关概念视频
Formation of Lipopolysaccharides
656
Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
656
Bulk Modulus
787
The bulk modulus is a scientific term used to describe a material's resistance to uniform compression. It is the proportionality constant that links a change in pressure to the resulting relative volume change.
787
Bulk Density of Aggregate
1.2K
Bulk density refers to the mass of aggregate particles that would fill a unit volume. The concept of bulk density originates from the inability to pack aggregate particles in a manner that completely eliminates void spaces. Hence, the term bulk refers to the volume that encompasses both the aggregates and the voids. This measurement is crucial when aggregates are batched by volume and is used to convert quantities by mass to volume.
Most natural mineral aggregates, like sand and gravel,...
Most natural mineral aggregates, like sand and gravel,...
1.2K
DNA Microarrays
21.2K
Microarrays are high-throughput and relatively inexpensive assays that can be automated to analyze large quantities of data at a time. They are used in genome-wide studies to compare gene or protein expression under two varied conditions, such as healthy and diseased states. Microarrays consist of glass or silica slides on which probe molecules are covalently attached through surface functionalization. Most commonly, the slides are prepared through the chemisorption of silanes to silica...
21.2K
Bacterial Transformation
60.1K
In 1928, bacteriologist Frederick Griffith worked on a vaccine for pneumonia, which is caused by Streptococcus pneumoniae bacteria. Griffith studied two pneumonia strains in mice: one pathogenic and one non-pathogenic. Only the pathogenic strain killed host mice.
Griffith made an unexpected discovery when he killed the pathogenic strain and mixed its remains with the live, non-pathogenic strain. Not only did the mixture kill host mice, but it also contained living pathogenic bacteria that...
Griffith made an unexpected discovery when he killed the pathogenic strain and mixed its remains with the live, non-pathogenic strain. Not only did the mixture kill host mice, but it also contained living pathogenic bacteria that...
60.1K
Bacterial Signaling
40.9K
Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
40.9K


