所有闪闪发光的都不是黄金:严格评估蛋白质化学模型的重要性
Polina Avdiunina1, Shamieraah Jamal1,2, Filipp Gusev1,2
1Department of Chemistry, Mellon College of Science, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States.
药物发现的蛋白化学模型 (PCM) 需要严格的评估. 数据分割和类不平衡对模型性能产生了重大影响,突出显示了机器学习/深度学习-PCM的概括性问题.
科学领域:
- 计算药物发现
- 化学信息学
- 药理学中的机器学习
背景情况:
- 蛋白化学模型 (PCM) 整合了蛋白质和配体数据以预测生物活性.
- 机器学习 (ML) 和深度学习 (DL) 在PCM中越来越多地使用,但缺乏一致的评估标准.
研究的目的:
- 评估影响ML/DL-PCM性能和通用性的关键因素.
- 评估数据修复,分离策略和蛋白质嵌入在酶-联体生物活性预测中的影响.
主要方法:
- 作为模型系统,利用了酶连接体生物活性预测.
- 研究了数据集策划,排列测试,类不平衡和数据分割策略.
- 评估了各种蛋白质配体描述和嵌入,包括多个序列对齐.
主要成果:
- 数据分割策略和类不平衡被确定为影响PCM表现的最关键因素.
- 突变测试表明,蛋白质嵌入对模型有效性起到最小的作用.
- 可信的数据泄露和嵌入质量显著影响模型的通用性.
结论:
- 严格的评估标准对于提高ML/DL-PCM对已退出分布的数据的概括性至关重要.
- 为了在药物发现中可靠的PCM开发,需要改进对比实践.
- 该研究强调了当前ML/DL-PCM实现强大的预测能力的挑战.
更多相关视频
10:37Deep Proteome Profiling by Isobaric Labeling, Extensive Liquid Chromatography, Mass Spectrometry, and Software-assisted Quantification
Published on: November 15, 2017
08:13Robust Comparison of Protein Levels Across Tissues and Throughout Development Using Standardized Quantitative Western Blotting
Published on: April 9, 2019
相关概念视频
Pharmacokinetic Models: Comparison and Selection Criterion
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.
Mechanistic Models: Compartment Models in Individual and Population Analysis
Analysis Methods of Pharmacokinetic Data: Model and Model-Independent Approaches
The model approach uses mathematical models to describe changes in drug concentration over time. Pharmacokinetic models help characterize drug behavior in patients, predict drug concentration in the body fluids, calculate optimum dosage regimens, and evaluate the risk of toxicity. However, ensuring that the model fits the experimental data accurately...
Physiological Pharmacokinetic Models: Assumption with Protein Binding
Mechanistic Models: Compartment Models in Algorithms for Numerical Problem Solving
In individual population analyses, different algorithms are employed, such as Cauchy's method, which uses a...
Mechanistic Models: Overview of Compartment Models
