GADRC:一种基于图形的方法,用于药物重新定位,使用深度残留网络和计算特征引导的低样本
Pengli Lu1, Mingxu Li2, Wenzhi Liu2
1School of Computer and Artificial intelligence, Lanzhou University of Technology, Lanzhou, 730050, Gansu, China. lupengli88@163.com.
Journal of computer-aided molecular design
|October 28, 2025
概括
本研究介绍了GADRC,这是一种用于药物重新定位 (DR) 的新方法,可以有效地识别现有药物的新用途. GADRC克服了当前计算方法的局限性,改善了药物疾病关联的发现.
科学领域:
- 计算生物学是一种计算生物学.
- 药理学 药理学是指药理学的学科.
- 生物信息学是一种生物信息学.
背景情况:
- 药物重新定位 (DR) 通过确定现有药物的新用途来加速治疗发现.
- 目前的计算DR方法在捕捉复杂的药物疾病关系和有效使用负样本方面存在局限性.
- 浅的网络架构和消失梯度问题阻碍了多层次交互的建模.
研究的目的:
- 开发一种先进的计算方法,GADRC,以克服当前药物重新定位策略的局限性.
- 加强对药物和疾病的本地和全球特征的提取.
- 改进负样本在药物疾病关联预测中的利用.
主要方法:
- 使用图形卷积网络和图形注意网络的协同架构来进行特征提取.
- 引入具有身份连接的深度残余网络,以解决网络深度退化问题.
- 使用特征导向的低样本策略和加权的交叉损失来有效地挖掘负样本.
主要成果:
- 在药物重新定位任务的三个基准数据集上,GADRC的表现始终优于现有方法.
- 该方法成功地捕获了本地药物结构特征和全球疾病途径特征.
- 实验结果表明,负样本的利用效率提高了.
结论:
- GADRC提供了一种强大而有效的方法来识别新药与疾病的关联.
- 该方法能够学习多层次交互和处理负样本的能力显著提升了计算DR.
- 关于阿尔茨海默病和乳腺癌的案例研究强调了GADRC在现实世界治疗发现方面的潜力.
相关概念视频
Drug Discovery: Overview
10.9K
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...
10.9K
Structure-Activity Relationships and Drug Design
1.7K
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
1.7K
Quantitative Aspects of Drug-Receptor Interaction
1.7K
The receptor occupancy theory connects a drug's response to the number of occupied receptors. With higher drug concentrations, more receptors are occupied, leading to increased responses. The formation of drug-receptor complexes involves association and dissociation rates, which reach equilibrium when the forward and backward reactions are equal. The equilibrium association constant (Ka) and its inverse, the equilibrium dissociation constant (Kd), indicate drug affinity. Higher Ka and lower...
1.7K
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
238
Pharmacokinetic models are mathematical constructs that represent and predict the time course of drug concentrations in the body, providing meaningful pharmacokinetic parameters. These models are categorized into compartment, physiological, and distributed parameter models.
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
238
Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
314
Noncompartmental analyses offer an alternative method for describing drug pharmacokinetics without relying on a specific compartmental model. In this approach, the drug's pharmacokinetics are assumed to be linear, with the terminal phase log-linear. This assumption allows for simplified analysis and interpretation of the drug's behavior in the body.
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
314


