可解释的机器学习模型用于预测高度单克隆抗体配方在超过和透过过程中的吉布斯-多南效应
Chyi-Shin Chen1, Seiryu Ujiie1, Reina Tanibata1
1API Process Development Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Biotechnology journal
|October 10, 2024
概括
这项研究使用机器学习模型来预测生物制药制造过程中蛋白质度的影响. 这些模型通过分析分子相互作用而加速过程开发,而无需进行广泛的实验.
科学领域:
- 生物制药工艺开发 生物制药过程开发
- 计算化学的计算化学
- 机器学习在药物发现中的作用
背景情况:
- 在超过/透过 (UF/DF) 过程中精确控制药物度,对于生物制药开发至关重要.
- 在UF/DF条件下理解辅助剂和蛋白质之间的分子相互作用是复杂的,需要专门的知识.
研究的目的:
- 开发基布斯-多南和体积排除效应在蛋白UF/DF中的预测模型.
- 利用简单的分子描述器来预测这些对氨基酸和单克隆抗体的影响.
- 为加速工艺开发提供传统UF/DF实验的in silico替代方案.
主要方法:
- 渐变增强树模型是使用分子描述器开发的.
- 信息获取和SHAP值用于模型解释和验证.
- 在 silico 预测与科学文献进行了交叉引用,并在试点规模制造中得到验证.
主要成果:
- 机器学习特征效应成功地被转化为现实世界的分子相互作用.
- 模型准确地预测了氨基酸和单克隆抗体的吉布斯-多南和体积排除效应.
- 在试点运行中的验证证实了这些模型对高度抗体产品的有效性.
结论:
- 开发的in silico模型为生物制药中的工艺开发提供了更快,更有效的方法.
- 这些模型通过合理解释分子机制来增强过程理解.
- 生物物理化学描述符和工艺条件是准确预测的足够输入,减少实验负担.
更多相关视频
07:53Activated Cross-linked Agarose for the Rapid Development of Affinity Chromatography Resins - Antibody Capture as a Case Study
Published on: August 16, 2019
9.2K
10:19Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing
Published on: February 13, 2016
11.3K
相关概念视频
Physiological Pharmacokinetic Models: Assumption with Protein Binding
35
Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
35
Dialysis
603
Dialysis is a diffusion-based purification process that separates analyte molecules from a complex matrix. This is accomplished by allowing molecules in the solution to pass through a semipermeable membrane into a liquid on the other side. The membrane is usually made of cellulose acetate or cellulose nitrate, and the second liquid must be miscible with the solution. Ions (e.g., chloride or sodium) or organic molecules (e.g., glucose) can pass through the membrane pores, which generally have...
603
