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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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磁盘CP-Atlas:一个全面的资源,将细胞过程映射到复杂疾病中.

Frank Qingyun Wang1, Caicai Zhang1, Hangchen Zhang2

  • 1Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong 999077, China.

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使用单细胞RNA测序数据,DisCP-Atlas将复杂的疾病与潜在的细胞过程联系起来. 本资源有助于通过将全基因组关联研究结果映射到连续细胞状态来揭示遗传风险机制.

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科学领域:

  • 基因组学就是基因组学.
  • 系统生物学 系统生物学
  • 计算生物学 计算生物学

背景情况:

  • 全基因组关联研究 (GWAS) 识别疾病基因,但与生物机制翻译作斗争.
  • 单细胞RNA测序 (scRNA-seq) 提供细胞解析,但目前的资源将疾病与离散细胞类型联系起来,缺少连续的细胞过程.
  • 遗传风险是由细胞过程中的基因表达程序驱动的,这些过程超越了传统的细胞类型界限.

研究的目的:

  • 开发DisCP-Atlas,一个全面的资源,将细胞过程映射到复杂疾病中.
  • 为了解疾病机制提供一个新的框架,专注于细胞过程,而不仅仅是细胞类型.
  • 为了使疾病对细胞过程进行双向查询,反之亦然.

主要方法:

  • 从35个人体组织的57个scRNA-seq数据集中获得了990个细胞过程,通过途径丰富和细胞类型活动进行注释.
  • 利用sc-linker框架系统地将1072个GWAS数据集 (759种疾病) 与已识别的细胞过程联系起来.
  • 开发交互式可视化和在线丰富工具,用于数据探索和定制基因分析.

主要成果:

  • 确定了37,918个细胞过程和疾病之间的显著关联.
  • DisCP-Atlas使用户能够查询疾病的基础细胞过程或识别与特定细胞程序相关的疾病.
  • 该资源提供可下载的结果和用于定制基因组分析的交互式在线丰富工具.

结论:

  • 通过专注于细胞过程,DisCP-Atlas弥合了GWAS发现和生物机制之间的差距.
  • 本资源有助于更深入地了解复杂疾病中的遗传风险.
  • DisCP-Atlas为研究人员提供了一个有价值的,可访问的平台,以探索与疾病相关的细胞程序.