暗激酶注释,挖掘和可视化使用蛋白激酶本体学
Saber Soleymani1, Nathan Gravel2, Liang-Chin Huang2
1Department of Computer Science, University of Georgia, Athens, GA, United States.
PeerJ
|December 11, 2023
概括
扩展的蛋白激酶本体学 (ProKinO) 知识图现在包括药物相互作用和表达数据. 这种增强的资源有助于发现对蛋白激酶 (如PAK5) 的新见解.
科学领域:
- 生物化学 生物化学
- 生物信息学是一种生物信息学.
- 基因组学就是基因组学.
背景情况:
- 蛋白激酶在细胞信号传递中至关重要,并与各种疾病有关.
- 现有的知识资源往往缺乏关于激酶序列,结构,功能和疾病关联的综合数据.
- 蛋白激酶本体学 (ProKinO) 为组织复杂的激酶信息提供了一个框架.
研究的目的:
- 显著扩展ProKinO知识图,包括表达模式和药物相互作用数据.
- 开发一个新的,交互式的Web浏览器,用于可视化和探索ProKinO知识图.
- 增强ProKinO的实用性,作为对未经研究的蛋白激酶及其在疾病中的作用的发现工具.
主要方法:
- 将表达模式和药物相互作用的额外数据集成到ProKinO知识图中.
- 开发了一个新的基于Web的浏览器,用于知识图的交互可视化.
- 利用图形挖掘和SPARQL查询来分析酶数据.
- 纳入酶连接体结合点,表达模式和功能特征到ProKinO.
- 集成的ProtVista用于3D结构和AlphaFold模型中激酶序列注释的交互式挖掘.
主要成果:
- 随着ProKinO的显著扩展,出现了新的类别和关系,包括酶连接体结合部位和表达模式.
- 为ProKinO开发了一个新的交互式Web浏览器,增强了可访问性和可用性.
- 图形挖掘确定了p21激活蛋白激酶5 (PAK5) 作为癌症中经常发生突变的"暗激酶",在急性髓性白血病中表达异常.
- 确定了PAK5中经常出现的瘤基因突变以及PAK家族激酶中常见的配体/药物结合残留物.
- 更新的ProKinO数据库和浏览器是公开可访问的.
结论:
- 扩展的ProKinO知识图及其交互式浏览器为信号社区提供了宝贵的资源.
- ProKinO促进了对蛋白质激酶的新见解的发现,特别是像PAK5.5这样的研究不足的蛋白质激酶.
- 这些发现突显了ProKinO在癌症研究和药物发现方面的潜力,通过识别关键突变和药物结合部位.
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