KGE-UNIT:基于知识图和药物发现多任务学习的分子相互作用预测的统一
Chengcheng Zhang1, Tianyi Zang1, Tianyi Zhao2
1Department of Computer Science, Harbin Institute of Technology, Harbin, 150001, China.
Briefings in bioinformatics
|February 13, 2024
概括
KGE-UNIT集成了知识图嵌入和多任务学习,同时预测药物标和药物相互作用,即使使用有限的数据,也提高了准确性.
科学领域:
- 生物信息学是一种生物信息学.
- 计算化学计算化学
- 药物发现 药物发现 药物发现
背景情况:
- 分子相互作用预测对于药物发现至关重要,但当前的方法往往无法利用任务之间的关系或遭受数据稀缺.
- 现有的方法经常孤立地处理预测任务,限制它们捕捉任务间依赖性和整体性能的能力.
研究的目的:
- 引入KGE-UNIT,这是一个统一的框架,结合了知识图嵌入 (KGE) 和多任务学习,用于同时预测药物向相互作用 (DTI) 和药物相互作用 (DDI).
- 通过利用共享信息和改进特征表示来提高单个任务的预测性能,特别是在数据有限的场景中.
主要方法:
- 利用KGE从药物知识图中提取异质特征,丰富药物和蛋白质节点的结构表示.
- 开发了一种创新的多任务学习预测器,其中包括基于任务意识的卷积神经网络 (CNN) 编码器和任务意识的注意力解码器,用于多式特征融合和上下文交互捕获.
主要成果:
- 在不平衡的数据集上,KGE-UNIT实现了卓越的性能,为DTI和DDI提供了高的AUROC和AUPR.
- 在数据有限的LUO数据集上表现出显著的性能增长,对于DTI和DDI预测,AUROC和AUPR的显著增加.
- 通过成功扩展到蛋白质-蛋白质相互作用预测来展示可扩展性,并通过切除和案例研究来验证有效性.
结论:
- KGE-UNIT提供了一种强大且统一的方法来预测分子相互作用,有效地解决数据稀缺问题并提高任务性能.
- 该框架能够同时从相关任务中学习并增强特征表示的能力使其成为加速药物发现和开发的有价值工具.
相关概念视频
Drug Discovery: Overview
7.9K
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...
7.9K
Structure-Activity Relationships and Drug Design
721
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...
721
Protein-protein Interfaces
12.5K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.5K
Ligand Binding Sites
12.8K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.8K
Quantitative Aspects of Drug-Receptor Interaction
982
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...
982
Drug-Receptor Bonds
2.8K
Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
In...
2.8K


