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Updated: May 22, 2025

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探索隐藏的危险:预测毒素类毒性和绘制肝细胞癌中毒学网络的地图

Jian Xiu¹, Hengzheng Yang¹, Xiaoli Shen¹

¹Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.

Journal of chemical information and modeling

|May 20, 2025

概括

菌毒素可以通过与细胞分子相互作用引起肝癌 (HCC). 这项研究使用机器学习来识别SRC和EGFR等关键蛋白质标,揭示了这些毒素如何破坏细胞信号通路.

科学领域:

毒理学毒理学毒理学
计算生物学计算生物学
肝病学肝病学是一种肝病学.

背景情况:

菌毒素是已知的致癌物,可触发肝细胞癌 (HCC).
它们涉及细胞巨分子和信号通路的精确机制仍然不完全理解.
了解这些相互作用对于开发有针对性的疗法至关重要.

研究的目的:

通过集成机器学习和生物分子分析,阐明菌毒素诱导的肝癌发生机制.
识别特定的真菌毒素集群及其相关的蛋白质-蛋白质相互作用网络.
为潜在的治疗策略提供对真菌毒素 - 大分子识别的结构性见解.

主要方法:

在1767种真菌毒素和1706种非真菌毒素真菌代谢物的数据集上评估了51种机器学习模型.
使用集群分析,网络毒理学,基因本体学 (GO) 丰富,KEGG通路分析和分子对接.
确定了关键调节蛋白 (EGFR,SRC,ESR1) 和它们的结合亲缘关系.

主要成果:

该KPGT机器学习模型表现出高性能 (ROC-AUC 0.979).
鉴定了六个不同的真菌毒素集群,具有独特的结构和蛋白质相互作用模式.
特定的真菌毒素集群显著调节了膜组织,囊泡运输,蛋白激酶和受体氨酸激酶通路.
集群5对SRC,EGFR和ESR1.1表现出强烈的结合亲和力.

结论:

机器学习和网络毒理学有效地确定了真菌毒素诱导的HCC中的关键分子参与者.
菌毒素集群表现出与SRC,EGFR和ESR1.1等关键细胞蛋白的明显相互作用概况.
这些发现为毒素 - 大分子相互作用提供了新的见解,并建议HCC的潜在治疗点.

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