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When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
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The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
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Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
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Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
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基础科学和病原发生学

Feixiong Cheng1, Yuan Hou1, Andrew A Pieper2,3,4,5

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概括
此摘要是机器生成的。

人工智能和机器学习工具与遗传数据相结合,可以识别新的阿尔茨海默病 (AD) 药物标. 这种方法揭示了EPHX2作为一个关键目标,并确定了可能减少AD发病率的现有药物.

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科学领域:

  • 基因组学就是基因组学.
  • 药物基因组学 药物基因组学
  • 计算生物学 计算生物学

背景情况:

  • 高通量测序已经为阿尔茨海默病 (AD) 产生了大量的遗传数据,但将这些发现转化为治疗仍然是一个挑战.
  • 缺乏有效的人工智能 (AI) 和机器学习 (ML) 工具阻碍了基因发现在临床实践中的应用.

研究的目的:

  • 开发和应用AI/ML方法,门德尔随机化 (MR) 和综合基因组数据,以确定AD的可用药物标.
  • 验证潜在的治疗点,并重新利用现有的AD治疗药物.

主要方法:

  • 利用来自多个大脑区域的eQTL和pQTL数据集的AI/ML,MR和大规模遗传/功能基因组数据.
  • 分析了来自275,540个AD病例和155万对照组的全基因组关联研究 (GWAS) 数据.
  • 采用人工智能辅助的药物协会研究,对约8000万个电子健康记录进行研究,以识别可重复使用的药物.

主要成果:

  • 确定了大约30个具有显著MR证据的可药物基因,包括环氧化酶2 (EPHX2) 作为关键的抗炎标.
  • 通过对iPSC衍生的神经元进行实验研究,验证了EPHX2在AD中的保护作用,在使用EPHX2抑制剂 (EC5026) 的小鼠模型中显示减少ptau181和改善认知.
  • 在111,680名轻度认知障碍患者中发现了12种药物,如特拉佐和巴克洛芬,与减少AD发病率有关.

结论:

  • 整合遗传和现实患者数据的AI/ML技术在识别AD治疗点和药物方面是有效的.
  • 对于候选标和药物,需要在不同人群中进行进一步的功能和临床验证.