在增强剂-促进剂区域重建蛋白相互作用的Penguin方法及其应用于前列腺癌的应用
Alexandros Armaos1, François Serra2,3, Iker Núñez-Carpintero2
1Istituto Italiano di Tecnologia, CHT@Erzelli, Via Enrico Melen 83, Building B, 7th floor, 16152, Genova, Italy.
Nature communications
|December 6, 2023
概括
我们开发了PENGUIN来绘制与增强剂-促进剂相互作用相关的蛋白质-蛋白质相互作用网络. 这种方法通过分析CTCF和前列腺癌单核酸多态性来识别潜在的前列腺癌基因和治疗点.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 增强剂-促进剂相互作用对于基因调节至关重要.
- 在这些调节元素中理解蛋白质与蛋白质相互作用 (PPI) 是复杂的.
- 目前的方法缺乏将增强剂-促进剂相互作用与PPI集成的能力.
研究的目的:
- 引入Promoter-Enhancer-Guided Interaction Networks (PENGUIN),这是一个研究PPI网络在增强器-促进器交互中的新方法.
- 通过将H3K27ac-HiChIP数据与组织特定的PPI集成来定义增强剂-促进剂PPI网络 (EPIN).
- 确定前列腺癌中潜在的功能影响和治疗点.
主要方法:
- 将H3K27ac-HiChIP数据与组织特异性PPI数据集成.
- 开发了PENGUIN计算方法.
- 在前列腺癌 (LNCaP) 和良性 (LHSAR) 细胞系中的验证.
- 分析EPIN集群用于丰富CTCF,前列腺癌单核酸多态 (PrCa SNPs) 和瘤基因.
- 使用CRISPR/Cas9淘汰和RNAi屏幕进行实验验证.
主要成果:
- 企成功定义了增强器-促进器 PPI 网络 (EPIN).
- EPIN集群被丰富了CTCF,这是增强剂-促进剂相互作用的关键调节器.
- 富含CTCF的EPIN与PrCa SNPs同时发生,这表明它们具有功能相关性.
- 这些EPIN还富含瘤基因,突出显示了它们在前列腺癌中的作用.
- 已识别的SNP被实验验证.
结论:
- 企为增强器-促进器交互和PPI网络之间的相互作用提供了新的见解.
- 该方法有助于识别关键基因和前列腺癌等疾病的潜在治疗点.
- 企为解剖复杂的基因调控网络提供了一种有价值的工具.
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