Machine learning extracts oncogenic‐specific γ‐H2AX foci formation pattern upon genotoxic stress
Machine learning extracts oncogenic‐specific γ‐H2AX foci formation pattern upon genotoxic stress
复制标题
机器学习提取基因毒性应激时致癌特异性 γ-H2AX 病灶形成模式
DOI：
10.1111/gtc.13005
复制
发表时间：
2023
期刊：
影响因子：
2.1
通讯作者：
Ikura Tsuyoshi
中科院分区：
文献类型：
--
作者：
Furuya Kanji;Ikura Masae;Ikura Tsuyoshi
H2 AX是一种组蛋白H2 A变体，在遗传毒性应激时变得磷酸化。磷酸化的H2 AX（γ-H2 AX）在DNA损伤反应中起抗癌作用，其病灶模式在强度和大小方面高度可变。然而，特征性γ-H2 AX灶模式是否与肿瘤发生（致癌特异性γ-H2 AX灶模式）相关仍不清楚。我们以前报道过TIP 60乙酰转移酶活性的缺陷促进了人类细胞系中癌细胞的生长。在这项研究中，我们通过使用机器学习比较了TIP 60野生型细胞和TIP 60 HAT突变细胞之间的γ-H2 AX灶模式。当仅关注γ-H2 AX病灶的强度和大小时，我们在所有γ-H2 AX病灶模式数据集中提取了TIP 60 HAT突变体样致癌特异性γ-H2 AX病灶模式。此外，通过使用降维方法UMAP，我们还在TIP 60野生型细胞中观察到TIP 60 HAT突变体样致癌特异性γ-H2 AX灶模式。总之，我们提出了致癌特异性γ-H2 AX灶模式的存在以及机器学习方法在γ-H2 AX灶变异中提取致癌信号的重要性。
H2AX is a histone H2A variant that becomes phosphorylated upon genotoxic stress. The phosphorylated H2AX (γ‐H2AX) plays an antioncogenic role in the DNA damage response and its foci patterns are highly variable, in terms of intensities and sizes. However, whether characteristic γ‐H2AX foci patterns are associated with oncogenesis (oncogenic‐specific γ‐H2AX foci patterns) remains unknown. We previously reported that a defect in the acetyltransferase activity of TIP60 promotes cancer cell growth in human cell lines. In this study, we compared γ‐H2AX foci patterns between TIP60 wild‐type cells and TIP60 HAT mutant cells by using machine learning. When focused solely on the intensity and size of γ‐H2AX foci, we extracted the TIP60 HAT mutant‐like oncogenic‐specific γ‐H2AX foci pattern among all datasets of γ‐H2AX foci patterns. Furthermore, by using the dimensionality reduction method UMAP, we also observed TIP60 HAT mutant‐like oncogenic‐specific γ‐H2AX foci patterns in TIP60 wild‐type cells. In summary, we propose the existence of an oncogenic‐specific γ‐H2AX foci pattern and the importance of a machine learning approach to extract oncogenic signaling among the γ‐H2AX foci variations.