机器学习辅助分类RASAR建模用于精选的一组口服活性药物的毒性潜力
Arkaprava Banerjee1, Kunal Roy2
1Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India.
这项研究开发了机器学习 (ML) 模型,使用分类阅读跨结构-活动关系 (c-RASAR) 方法来预测药物毒性. 最好的c-RASAR模型准确地识别了药物的潜在脏毒性,有助于更安全的药物开发.
科学领域:
- 计算化学是一种计算化学.
- 毒理学 毒理学 毒理学
- 药物发现 药物发现
背景情况:
- 药物诱导的毒性是制药开发中的一个重大问题.
- 预测模型可以帮助在药物发现过程的早期确定潜在的毒性.
研究的目的:
- 开发和验证机器学习 (ML) 模型,以使用分类阅读跨结构-活性关系 (c-RASAR) 方法预测药物毒性.
- 确定用于选已知毒化合物的外部数据集的最佳性能模型.
主要方法:
- 开发36个ML模型,包括18个QSAR模型和18个c-RASAR模型,使用拓描述符和MACCS指纹.
- 严格的交叉验证 (20次,五次) 和在测试套件上的外部验证.
- 应用排名差异总和 (SRD) 方法用于多标准模型选择.
主要成果:
- 在预测毒性方面,c-RASAR模型的整体表现良好.
- 性能最好的模型是从拓描述器衍生出的线性差异分析 (LDA) c-RASAR模型,达到0.229 (训练) 和0.431 (测试) 的MCC值.
- 这种顶级模型在应用于DrugBankDB的外部数据集时显示出良好的预测性.
结论:
- 在开发药物毒性预测模型时,c-RASAR方法是有效的.
- 经过验证的LDA c-RASAR模型可以可靠地选潜在脏毒性的化合物.
- 这种预测能力支持开发更安全的口服活性药物.
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