用图形神经网络和转录组分析纠正的互动组网络来重新定位粉样性粉样性粉样性粉样性粉素的药物
Shan He1, XiaoYing Lv2, XinYue He1
1Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Human gene therapy
|September 27, 2023
概括
计算药物重新定位发现了针对粉样蛋白转化素 (ATTR) 粉样蛋白症的新疗法候选者. 这项研究分析了基因表达和蛋白质网络,以寻找可能治疗这种罕见的进展性疾病的药物.
科学领域:
- 基因组学和生物信息学
- 药理学和药物发现
- 罕见疾病研究研究 罕见疾病研究
背景情况:
- 氨基胺转化蛋白 (ATTR) 氨基粉症是一种罕见的,进展性疾病,其特点是神经和心脏中错误折叠的转化蛋白蛋白蛋白沉积物.
- 目前的疗法只能提供症状缓解,预后不好,没有可用的治疗方法.
- 药理和基因组数据的进步为通过计算药物重新定位的新疗法发现提供了机会.
研究的目的:
- 通过计算药物重新定位来识别ATTR氨基粉症的潜在新药候选者.
- 为了利用大规模的基因组,转录组和药理学数据进行新型治疗查.
主要方法:
- 从公共数据库收集了与ATTR相关的基因,以及从表达特征中分别表达的基因.
- 构建了一个纠正的蛋白质-蛋白质相互作用网络,并使用DrugBank目标选候选药物.
- 使用图形神经网络精制的候选药物,并通过反向基因组丰富分析评估化合物扰动效应.
主要成果:
- 从转录组数据中确定了139个ATTR相关基因和56个差异表达基因.
- 根据网络接近ATTR基因,选了355种潜在的候选药物.
- 通过基因表达干扰分析验证候选药物的疗效,识别高概率的候选药物.
结论:
- 系统的计算药物重新定位整合互动组网络和转录组数据是有效的识别新型ATTR氨基粉症治疗方法.
- 确定了几种有前途的候选药物,为ATTR粉样化症提供了潜在的新治疗途径.
- 这种方法为发现用于治疗未满足治疗需求的罕见疾病的药物提供了强大的框架.
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