一种机械神经网络模型预测了抗微生物组合疗法的效力和毒性
Harkirat Singh Arora1, Katherine Lev2, Aaron Robida3
1Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, US, 48105.
medRxiv : the preprint server for health sciences
|April 1, 2025
概括
抗微生物耐药性是一种全球性威胁. 一种新的数据驱动方法CALMA预测药物组合,提高功效和降低毒性,改善抗微生物治疗.
科学领域:
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
- 计算生物学 计算生物学
背景情况:
- 抗菌素耐药性 (AMR) 是一个关键的全球健康挑战,需要新的治疗策略.
- 目前针对AMR的组合疗法往往缺乏最佳效果和显著毒性.
- 药物组合的实验查是昂贵和耗时的,突出了对预测模型的需求.
研究的目的:
- 引入CALMA,一种用于预测抗微生物多药组合功效和毒性的计算方法.
- 为了确定协同作用的抗微生物组合,减少对大肠杆菌和结核菌的毒性.
- 提高药物相互作用预测模型的可解释性.
主要方法:
- 卡尔马集成机械模型与深度学习技术.
- 该方法用于预测大肠杆菌和结核菌的药物组合.
- 验证涉及*体外*细胞活力测定和患者病历分析.
主要成果:
- 卡尔玛确定了具有对抗性毒性的协同作用的万科米辛和异化组合.
- 实验验证证证实了预测的协同作用和对抗作用.
- 挖掘患者数据显示,使用CALMA识别组合的患者的副作用减少.
结论:
- 卡尔马提供了一个数据驱动的策略,以优化抗微生物组合治疗.
- 这种方法成功地预测了强效和毒性较低的药物组合.
- 卡尔马提高了对药物相互作用的理解,并有助于开发更安全,更有效的AMR治疗方法.
相关概念视频
Combined Effects of Drugs: Synergism
3.6K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
3.6K
Mechanistic Models: Overview of Compartment Models
49
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...
49
Pharmacokinetic Models: Comparison and Selection Criterion
27
Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
27
Pharmacokinetic Models: Overview
515
Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
515
Agonism and Antagonism: Quantification
265
When drugs are administered, they can elicit either an agonist or antagonist effect on the body. Agonism occurs when a drug activates a specific receptor, triggering a biological response. On the other hand, antagonism happens when a drug binds to the same receptors but blocks their activation, thereby preventing a biological response.
To quantify these effects, researchers use a dose-response curve, which provides valuable information about the potency and efficacy of a drug. Potency refers to...
To quantify these effects, researchers use a dose-response curve, which provides valuable information about the potency and efficacy of a drug. Potency refers to...
265
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
48
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...
48


