疟疾流:一个全面的深度学习平台,用于多个阶段的表型抗疟疾药物发现
Mujie Lin1, Junxi Cai2, Yuancheng Wei3
1School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, China.
European journal of medicinal chemistry
|August 22, 2024
概括
FP-GNN深度学习模型在跨寄生虫阶段预测抗疟疾药物活性方面表现出卓越的表现. 这种方法有助于通过有效分析用于疟疾药物发现的大型复合数据集来发现新的治疗方法.
科学领域:
- 计算化学和药理学计算化学和药理学
- 机器学习在药物发现中的应用.
- 寄生虫学和传染病研究.
背景情况:
- 疟疾的耐药性和传播对全球健康构成重大挑战.
- 对于抗疟疾药物发现的现有机器学习 (ML) 和深度学习 (DL) 方法需要进一步优化.
- 当前的研究往往忽视了各种寄生虫菌株和多阶段活动预测.
研究的目的:
- 系统地比较各种ML和DL模型对抗疟疾活动预测的性能.
- 评估不同类型的Plasmodium寄生虫表型和生命周期阶段的模型.
- 确定用于加速抗疟疾药物发现的先进计算策略.
主要方法:
- 策划了407,404个化合物和410,654个生物活性点的大型基准数据集.
- 基于指纹的ML (RF::Morgan,XGBoost:Morgan) 和基于图形的DL模型 (GCN,GAT,MPNN,注意力FP) 的比较.
- 评估的共同代表性DL模型 (FP-GNN,HiGNN,FG-BERT) 用于结合化学知识.
主要成果:
- FP-GNN模型实现了最高的预测性能,AUROC为0.900.
- 共同代表性DL模型,特别是FP-GNN,通过整合化学知识而脱而出.
- 基于指纹的ML模型在较大的数据集上是有效的,但DL模型在集成功能时表现更好.
结论:
- 在多个寄生虫阶段,FP-GNN对抗疟疾活性具有卓越的预测能力.
- 共同代表的DL模型提供了一个有希望的方法,通过利用化学洞察力来增强抗疟疾药物的发现.
- 开发的MalariaFlow网络服务器有助于预测,查和发现新的多阶段抗疟疾药物候选药物.
相关概念视频
01:26Drug Discovery: Overview
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
01:26Drug Administration and Therapy Phases: Overview
Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
01:16Therapeutic Drug Monitoring: Overview and Classification
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood at designated intervals to ensure the drug concentration stays within a therapeutic range. This monitoring is crucial for optimizing individual dosage regimens, enhancing therapeutic efficacy, and minimizing drug-related toxicity. TDM is vital for drugs with narrow therapeutic windows, significant variability in pharmacokinetics, and a clear correlation between plasma levels and...
01:29Therapeutic Drug Monitoring: Affecting Factors
Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
01:26Therapeutic Drug Monitoring: Drug Analysis Methods
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood or body tissues to tailor drug therapy effectively. This monitoring is critical for managing drugs with narrow therapeutic indices like digoxin and phenytoin, ensuring they are both safe and effective. For instance, monitoring theophylline levels in asthma patients involves precision and sensitivity to adjust doses according to individual responses to therapy, ensuring efficacy and...
01:24Modified-Release Drug Delivery Systems: Site-Targeted
Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.