发现药物的作用机制具有稀疏可解释的网络
Katyna Sada Del Real1, Angel Rubio2
1Departamento de Ingeniería Biomédica y Ciencias, TECNUN, Universidad de Navarra, San Sebastián 20018, Spain.
EBioMedicine
|August 26, 2023
概括
SparseGO是一种新型稀疏和可解释的神经网络,增强了对癌症药物反应的预测和理解. 这种可解释的AI方法提高了准确性和效率,使药物重新定位和作用机制发现成为可能.
科学领域:
- 计算生物学是一种计算生物学.
- 人工智能在瘤学中的应用
- 药物的发现和开发.
背景情况:
- 深度神经网络 (DNN) 在预测癌症药物疗效方面表现有前途,但缺乏解释性.
- 之前的解释方法需要大量的GPU资源,并且限制了全基因组应用.
- 可解释性AI (XAI) 对于理解复杂的生物模型至关重要.
研究的目的:
- 开发一种稀疏且可解释的神经网络,用于预测癌症药物反应和作用机制 (MoA).
- 提高DNN在药物发现中的基因组数据分析的效率和可扩展性.
- 整合XAI技术来发现新的药物MoAs.
主要方法:
- 开发了 SparseGO,一个稀疏且可解释的神经网络.
- 集成的DeepLIFT (XAI) 与支持矢量机器用于MoA发现.
- 在多个数据集上训练和评估SparseGO,使用交叉验证,利用基因表达数据.
主要成果:
- 与现有方法相比,SparseGO显著减少了GPU内存使用量和训练时间.
- 使用基因表达作为输入提高了预测准确性,并使药物重新定位.
- 成功预测了265种药物的MoA,并对未经研究的化合物进行了验证.
结论:
- SparseGO是一种有效的XAI方法,用于预测和理解癌症药物反应.
- 该模型的效率和可解释性促进了在精密瘤学中的更广泛应用.
- SparseGO在生物医学研究中推进了可解释的人工智能领域.
更多相关视频
13:18Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma
Published on: March 3, 2023
1.3K
12:34Author Spotlight: Exploring ShiDuGao's Multi-Target Approach in Anus Eczema Treatment
Published on: January 12, 2024
847
相关概念视频
01:24Principles of Drug Action
6.1K
Drugs are chemical substances that modify biological responses by interacting with macromolecular targets such as receptors, ion channels, transporters, and enzymes. Pharmacodynamics describes the course of action of drugs leading to the physiological effect at a specific site in the body.
Drugs can be agonists or antagonists. Like the endogenous ligands, agonists always bind and activate the target to produce a cellular response. Agonist binding induces a conformational change which in turn...
Drugs can be agonists or antagonists. Like the endogenous ligands, agonists always bind and activate the target to produce a cellular response. Agonist binding induces a conformational change which in turn...
6.1K
01:26Targets for Drug Action: Overview
6.4K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
6.4K
01:21Pharmacodynamics: Overview and Principles
1.2K
Pharmacodynamics is a scientific field that delves into drugs' intricate biochemical, cellular, and physiological effects on the human body. The study of pharmacodynamics helps us understand how drugs interact with the body and elicit various responses.
Most drugs' effects result from their interactions with drug receptors or targets within the body. These interactions trigger specific responses at the cellular or systemic level. Drug receptors can be found on the surfaces of cells or...
Most drugs' effects result from their interactions with drug receptors or targets within the body. These interactions trigger specific responses at the cellular or systemic level. Drug receptors can be found on the surfaces of cells or...
1.2K
01:26Neurochemical Transmission: Sites of Drug Action
2.5K
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
2.5K
01:29Drug-Receptor Interactions
5.3K
Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
5.3K
01:21Mechanistic Models: Overview of Compartment Models
112
Mechanistic models, a category encompassing both physiological and compartmental modeling, differ from empirical models' approaches to incorporating known factors about the systems being modeled. Empirical models describe data with minimal assumptions, while mechanistic models aim to provide a robust description of available data by specifying assumptions and integrating known factors about the system. Compartmental analysis is a key example of a mechanistic model in pharmacokinetics and...
112