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解锁肝脏生理学:为机械学理解提供全面的路径图

Luiz Ladeira¹, Anouk Verhoeven², Jonas van Ertvelde²

¹Biomechanics Research Unit, GIGA Institute, University of Liège, Liège, Belgium.

Frontiers in toxicology

|July 22, 2025

概括

使用in silico方法创建了两个新的肝脏生理地图 (PM),以推进化学安全评估. 这些互动地图详细介绍了肝脂和胆酸通路,有助于肝毒性和药物发现的研究.

科学领域:

* 计算毒理学和系统生物学.
*生物信息学和途径分析.
* 新型方法方法 (NAMs).

背景情况:

* 化学安全的传统动物试验正在被先进的in silico方法所取代.
*生理地图 (PMs) 提供了一种结构化的方式来表示复杂的生物机制.
*肝功能对化学代谢和毒性至关重要,需要详细的机制理解.

研究的目的:

*为肝脏关键功能引入两种新的,机器可读的肝脏生理地图 (PMs).
* 提供交互式,精心策划的肝脂代谢和胆酸通路的图形表示.
* 支持开发与人体相关的体外试验策略,用于化学品安全评估.

主要方法:

*手册文学策划和路径资源和专家知识的整合.
*使用人类蛋白质图谱数据集验证细胞类型特异性.
*与现有的不利结果途径 (AOP) 网络进行交叉比较,以确定覆盖范围和差距.

主要成果:

*开发了LiverLipidPM和LiverBilePM,详细介绍了特定的代谢和运输途径.
* 交互式地图允许可视化,外部本体学链接和实验数据叠加.
*确定了用于AOP扩展的新型化学标和潜在的分子启动事件.

结论:

*肝脏PM是肝病学,肝毒性研究和AOP改进的宝贵资源.
* 这些地图促进了计算模型和操作模式本体学的发展.
*PM可以扩展到系统生物学,药物发现和体外试验电池开发.

关键词:

肝脏病学肝脏病学新方法方法论新方法方法论生理地图,生理地图.系统生物学系统生物学毒理学毒理学毒理学

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