数据质量和数据量对内在可溶性估计的影响:基于单一来源数据集的分析
Jiaxi Zhao1, Eline Hermans2, Kia Sepassi3
1Department of Pharmacy, Uppsala University, 751 23 Uppsala, Sweden.
Molecular pharmaceutics
|September 13, 2024
概括
高质量的数据改善了制药溶解性预测. 即使是大型,杂的数据集也可以产生准确的结果,但关键数据审查对于避免偏见错误和提高药物发现模型性能至关重要.
科学领域:
- 药物的发现和开发.
- 计算化学是一种计算化学.
- 药理动力学 药理动力学
背景情况:
- 水溶性是影响口服药物吸收的关键物理化学性质.
- 目前的in silico模型难以预测新化学空间的溶解度.
- 来自约翰逊和约翰逊公司的大型,高通量水溶性数据集为模型改进提供了独特的资源.
研究的目的:
- 研究数据质量和数量的对in silico可溶性预测模型的影响.
- 在新的化学空间中,确定模型性能有限的原因.
- 开发改进的方法来预测内在的水溶性.
主要方法:
- 使用不同的数据处理方法生成了六个具有不同大小和噪声水平的内在溶解度数据集.
- 使用RDKit,ADMET预测器和Mordred的描述符训练随机森林回归器.
- 使用嵌套交叉验证和精细测试集评估模型性能.
主要成果:
- 高质量的数据始终导致给定数据集大小的更好的模型性能.
- 具有分析可变性的较大数据集可以达到与较小,更清洁的数据集可比的准确性.
- 来自无形固体残留物的噪声显著影响预测,并且不能通过增加数据大小来克服,这强调了对数据质量控制的需求.
结论:
- 对于可靠的in silico可溶性预测,关键数据审查和策划至关重要.
- 一个单一来源的精选数据集显著提高了内在可溶性的预测.
- 优化的模型在基准可溶性挑战数据集上取得了卓越的性能.
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