一个整合性系统生物学策略,以支持不良结果途径 (AOPs) 的发展:关于辐射诱导的小头的案例研究
Thomas Jaylet1, Roel Quintens2, Olivier Armant3
1Université Paris Cité, Inserm T3S, Paris, France.
Frontiers in cell and developmental biology
|July 10, 2023
概括
使用系统生物学策略来简化开发不利结果途径 (AOPs). 这种方法选数据库和文献以确定关键事件,帮助评估毒理风险.
科学领域:
- 毒理学和环境健康
- 系统生物学 系统生物学
- 计算生物学 计算生物学
背景情况:
- 不良结果途径 (AOPs) 对于化学品和污染物等压力因素的风险评估至关重要.
- 识别分子启动事件 (MIE) 和关键事件 (KE) 是AOP开发的一个重大挑战.
- 目前的AOP开发缺乏有效的方法来识别生物事件之间的机制联系.
研究的目的:
- 提出和验证一个系统生物学策略,以简化AOP开发.
- 帮助研究人员识别潜在的关键事件 (KE) 和支持AOPs的文献.
- 通过新的机制性见解来促进现有AOP的丰富.
主要方法:
- 利用系统生物学方法整合公共数据库和文献挖掘.
- 使用文本挖掘工具AOP-helpFinder来有效选和识别KE.
- 进行路径和网络分析以阐明生物事件之间的机制关系.
主要成果:
- 拟议的战略成功地确定了潜在的KE和AOP开发的相关文献.
- 应用到AOP 441 (辐射诱导的小头) 证实了现有的KE和确定了新的KE.
- 该方法证明了效率和易用性,只需要压力因素和不良结果信息.
结论:
- 系统生物学策略显著简化和增强了不良结果途径的发展.
- 这种方法支持在毒理学中推进替代方法,减少对传统测试的依赖.
- 经过验证的战略为毒理学家和环境健康科学家提供了有价值的工具.
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