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在RAS-MAPK系统中使用转移测量的信息流的评估

Nobuhisa Umeki¹, Yoshiyuki Kabashima^2,3, Yasushi Sako¹

¹Cellular Informatics Laboratory, RIKEN, Cluster for Pioneering Research, Wako, Japan.

|March 6, 2025

概括

使用转移的信息流分析揭示了RAS-MAPK通路中的反调节. 该方法准确地绘制复杂的细胞信号网络,并识别与疾病相关的突变,为分子药理学和病理学提供新的见解.

科学领域:

细胞信号传输和分子生物学
系统生物学系统生物学
药理学和病理学药理学和病理学

背景情况:

RAS-MAPK通路对于细胞生长和分化等过程至关重要,其失调与癌症和遗传疾病有关.
了解这种途径中的复杂调节机制对于开发向疗法至关重要.

研究的目的:

应用信息流分析,特别是转移 (TE),以阐明RAS-MAPK系统中SOS和RAF之间的调节动态.
探索 TE 作为一种评估信息流动和识别蜂信号监管网络的无模型方法的潜力.

主要方法:

利用转移 (TE) 来分析EGF刺激细胞中SOS (氨酸核酸交换器RAS) 和RAF (RAS效应激酶) 之间的激活动态.
采用无模型方法来量化细胞系统内的信息流的时间,方向和强度.
通过使用MEK抑制剂和分析与努南综合征相关的SOS突变,验证了TE发现.

主要成果:

在SOS和RAF之间检测到显著的双向信息流 (TE),表明RAS-MAPK通路内的反调节.
证明TE是一种独特的测量,独立于输入剂量或因果反应强度.
提出了一个具有多个路径和反循环的监管网络模型,包括时间切换,经过实验证实.
鉴定了与努南综合征相关的SOS突变中的功能障碍,揭示了其致病机制.

结论:

转移是一种强大的,无模型的工具,用于剖析像RAS-MAPK这样的细胞信号通路中的复杂的调节网络.
TE分析为途径动态,反机制以及遗传突变的功能后果提供了新的见解.
这种方法对推进分子药理学和理解信号通路失调驱动的疾病病理学具有重大前景.

关键词:

在RAS/MAPK系统中.计算生物学是计算生物学.人类人类人类人类人类人类人类信号处理信号处理信号处理一个单细胞分析.系统生物学系统生物学转移是转移的一种.

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