非向的代谢组学,用于识别与有机离子载体聚1B1功能相关的血代谢物
Kreetta Hämäläinen1,2, Päivi Hirvensalo1,2,3, Mikko Neuvonen1,2
1Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.
Clinical and translational science
|March 22, 2024
概括
这项研究确定了甘二氧化3-O-糖化物 (GDCA-3G) 和甘二氧化3-O-糖化物 (GCDCA-3G) 作为有机阴离子输送聚1B1 (OATP1B1) 功能的可靠生物标志物. 这些来自代谢学分析的发现为OATP1B1活动评估提供了新的见解.
科学领域:
- 药理学 药理学是指药理学的学科.
- 代谢学 代谢学 代谢学
- 生物标志物发现发现
背景情况:
- 有机离子运输聚1B1 (OATP1B1) 在药物和代谢物运输中起着至关重要的作用.
- 准确评估OATP1B1功能对于个性化医学和药物开发至关重要.
- 评估OATP1B1功能的现有方法可能需要提高效率和全面性.
研究的目的:
- 为了确定有机离子载体聚1B1 (OATP1B1) 功能的新型血生物标志物.
- 用一种无假设的代谢学方法来进行无偏见的生物标志物发现.
- 使用可靠的统计和机器学习方法验证已识别的生物标志物.
主要方法:
- 分析了356名健康志愿者的禁食血样本中的9152个分子特征,使用液体染色学高分辨率质谱学.
- 根据SLCO1B1基因型,将志愿者分为OATP1B1功能组进行分层.
- 应用线性回归,随机森林 (RF) 和梯度增强决策树 (GBDT) 模型,将代谢物特征与OATP1B1功能关联起来.
主要成果:
- 39个分子特征与OATP1B1功能有显著的关联.
- 甘氨酸二氧化3-O-糖化物 (GDCA-3G) 和甘氨酸二氧化3-O-糖化物 (GCDCA-3G) 呈现出最强的关联.
- 在不同的分析模型中,GDCA-3G和GCDCA-3G被证实是人类血中OATP1B1功能的强大的生物标志物.
结论:
- 甘二氧化酸3-O-糖化物 (GCDCA-3G) 和甘二氧化酸3-O-糖化物 (GDCA-3G) 已被验证为OATP1B1功能的可靠血生物标志物.
- 没有假设的代谢学方法成功地确定了OATP1B1活性的新生物标志物.
- 这些生物标志物有可能改善对OATP1B1介导药物处置和患者风险分层的评估.
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