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CTAS:一种基于网络控制理论的方法,用于识别在上皮细胞-介质细胞过渡过程中AS事件的关键监管TF

Yan Gan¹, Yangsong He¹, Pu Zhao²

¹School of Mathematical Sciences, Shenzhen University, 3688 Nanhai Avenue, Nanshan District, Shenzhen, Guangdong 518061 China.

Briefings in bioinformatics

|February 10, 2026

概括

我们开发了CTAS,这是一种新的计算方法,用于识别在表皮-介质细胞过渡 (EMT) 期间调节替代拼接 (AS) 的转录因子 (TF). CTAS揭示了像HOXA3这样的关键TF,控制了对细胞可塑性和转移至关重要的AS事件.

科学领域:

分子生物学分子生物学
计算生物学计算生物学
基因组学就是基因组学.

背景情况:

替代拼接 (AS) 产生了转录基因多样性,对表皮细胞-介质细胞过渡 (EMT) 至关重要.
监管机制,特别是在EMT期间控制AS的转录因子 (TF),尚未完全理解.
现有的计算方法很难从大量数据中解读多层TF-RBP-AS监管级联.

研究的目的:

开发一种计算方法,CTAS,用于识别在EMT期间调节AS事件的关键TF.
推断TF,RNA结合蛋白 (RBPs) 和AS事件的动态调控网络.
为了发现与EMT相关的AS.新型TF监管器.

主要方法:

CTAS集成了伪时序,趋势分析,稀疏定向网络推断和控制理论选.
该方法使用模拟进行了验证,在重建EMT轨迹和网络方面实现了高准确性.
应用于TCGA BRCA数据,CTAS构建了一个TF$\to $RBP$\to $AS监管网络.

主要成果:

CTAS准确地重建了模拟的EMT轨迹 (斯皮尔曼的$\rho = 0.99946$) 和网络 (ROC AUC = 89.9%).
对TCGA BRCA数据的分析确定了HOXA3,PRDM8和TWIST2作为EMT相关AS的顶级TF控制器.
九个AS事件显示出显著的动态转变,CD44子网络中突出显示了ZNF521和HIC1.

结论:

CTAS有效地将横截面数据转化为动态的监管见解.
已确定的TFs (HOXA3,PRDM8,TWIST2,ZNF521,HIC1) 是EMT期间AS的潜在关键调节者.
这种方法为了解EMT和转移提供了可以通过实验测试的假设.

关键词:

控制理论控制理论表皮介质介质的过渡.伪时间分析分析.监管网络监管网络监管网络监管网络监管

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