使用概率机器学习预测与肝功能相关的体外测试.
Flavio M Morelli1, Marian Raschke2, Natalia Jungmann2
1R&D Machine Learning Research, Bayer AG, Pharmaceuticals Division, Berlin, Germany; Department of Mathematics and Computer Science, Free University of Berlin, Berlin, Germany.
Toxicology
|May 21, 2025
概括
这项研究将多种数据类型集成到一个概率框架中,以预测体外肝毒性,量化预测不确定性,以获得更安全的药物开发和减少动物试验.
科学领域:
- 毒理学 毒理学 毒理学
- 计算生物学 计算生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 机器学习 (ML) 在毒理学中越来越多地使用,但有限的数据需要量化in silico预测的不确定性.
- 在毒理学评估中可靠的决策需要强大的不确定性量化方法.
研究的目的:
- 开发和评估一个概率框架,用于预测体外肝检测结果,使用综合数据模式.
- 量化与这些in silico预测相关的不确定性.
- 将预测整合到药物诱导肝损伤 (DILI) 概率的估计中.
主要方法:
- 系统地比较各种概率方法来预测体外肝功能测试.
- 整合多种数据模式:化学描述符,基因表达和形态资料.
- 为生成活性氧物种和肝细胞毒性测试生成新的实验数据.
主要成果:
- 在概率框架内证明了不同数据模式的性能.
- 成功整合了框架和体外测试预测,以估计DILI概率.
- 提供了新的肝细胞毒性和反应性氧物种生成的实验数据.
结论:
- 不确定性量化对于可靠的in silico毒性预测至关重要.
- 开发的概率框架提高了体外测试和DILI风险的预测.
- 这种方法可以促进更安全的药物开发过程,并减少动物试验.
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