通过网络毒理学分析和深度学习预测,环境生物毒素okadaic酸的毒性影响
Dongyao Wang1, Ying Zhang2, Yao Yang3
1Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
Aquatic toxicology (Amsterdam, Netherlands)
|September 23, 2025
概括
网络毒理学和深度学习将AKT1确定为甲酸 (OA) 神经毒性的关键目标. 这种方法有助于理解OA诱导的大脑损伤,并为贝类中毒的治疗策略提供信息.
科学领域:
- 环境毒理学环境毒理学
- 计算生物学 计算生物学
- 神经科学是一个神经科学.
背景情况:
- 酸 (OA) 是一种强大的海洋生物毒素,是导致腹的贝类中毒的原因.
- 了解OA的神经毒性机制对于公共卫生和环境安全至关重要.
- 现有的研究毒素机制的方法可能是低效的,缺乏机械精度.
研究的目的:
- 开发和应用一个集成的网络毒理学和深度学习策略,以阐明OA的神经毒性.
- 确定关键的分子标和涉及OA诱导神经毒性的途径.
- 为了解和治疗OA相关的脑损伤提供理论基础.
主要方法:
- 网络毒理学方法使用K-means集群来识别与OA暴露相关的95个枢纽目标.
- 深度学习策略采用DeepPurpose算法,在微观水平上精确定位关键的分子目标.
- 分子对接和生物层干涉测量以验证OA和确定关键目标之间的相互作用.
主要成果:
- 确定了95个与OA诱导的腹和神经毒性相关的枢纽目标.
- 通过深度学习,确定AKT1作为OA神经毒性的关键分子标.
- 实验验证证了OA和AKT1 (KD=6.61E-11 M) 之间强烈的结合相互作用.
结论:
- 网络毒理学和深度学习的协同集成为研究复杂的毒理学机制提供了一种强大的多层次方法.
- AKT1是OA诱导的神经毒性的关键分子标,为OA相关的大脑损伤提供了洞察力.
- 这项研究为开发针对生物环境或食品传播OA暴露的有针对性的干预措施奠定了基础.
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