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对高通量转录组学的全面分析,以区分药物诱导性肝损伤 (DILI) 现型
Sangyeon Shin1, Chanhee Lee1, Taesung Park2,3
1Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea.
Archives of toxicology
|June 4, 2025
概括
高通量转录组学 (HTTr) 显示出预测药物诱导肝损伤 (DILI) 的前景. 将基因表达与化学数据相结合,可以改善DILI分类和药物安全性评估.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 基因组学和生物信息学
背景情况:
- 药物诱导性肝损伤 (DILI) 在药物开发中带来了重大挑战.
- 高通量转录组学 (HTTr) 提供了对药物肝毒性的机制性见解,补充了传统方法.
研究的目的:
- 评估HTTr数据对分类和预测DILI的有用性.
- 探索转录组和化学结构数据的整合,以提高DILI预测.
主要方法:
- 审查现有的基于HTTr的DILI研究,数据集和计算工具.
- 对146种药物的TG-GATE开放数据库中初级人类肝细胞基因表达数据的分析.
- 机器学习模型的应用,整合基因表达和化学结构数据.
主要成果:
- 仅基因表达数据就显示了有限的DILI分类能力,与基于结构的模型相比.
- 目标基因组增强了聚类性能,度水平影响了毒性分析.
- 整合基因表达和化学结构数据显著提高了预测准确度.
结论:
- HTTr是推进DILI分类和预测的宝贵工具.
- 结合转录组和化学数据的多模式方法对于可靠的药物安全性评估至关重要.
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