在CHO种植中交叉克隆拉曼校准模型的可行性和性能
Rafael Machleid1,2, Marek Hoehse1, Steffi Scholze1
1Sartorius Stedim Biotech GmbH, Göttingen, Germany.
Biotechnology journal
|November 28, 2023
概括
拉曼光谱精确监测细胞系发育中的葡萄糖和乳酸盐. 然而,使用拉曼模型预测标位需要考虑克隆差异,因为生产力变化可能会引入重大偏差和预测错误.
科学领域:
- 生物技术是生物技术.
- 过程分析技术 (PAT) 是一种分析技术.
- 生物制药制造业 生物制药制造业
背景情况:
- 拉曼光谱是建立用于监测生物制药细胞培养的.
- 它在细胞系发育 (CLD) 中用于监测培养参数的应用较少被探索.
- 克隆变异对CLD拉曼模型性能的影响尚不清楚.
研究的目的:
- 调查克隆差异对拉曼光谱校准模型对预测位数,葡萄糖和乳酸盐的影响.
- 评估这些模型在细胞系开发阶段的准确性和可转移性.
- 为了确定由克隆异质性产生的拉曼模型中的潜在偏差.
主要方法:
- 开发Raman OPLS模型,用于预测标位,葡萄糖和乳酸.
- 使用了11个具有不同生产率和生长率的中国仓鼠卵巢 (CHO) 克隆.
- 在交叉验证的预测上使用克隆智能线性回归评估与克隆相关的偏差.
主要成果:
- 拉曼模型准确地预测了葡萄糖和乳酸,不受克隆差异的影响.
- 提特预测模型显示了与克隆相关的重大偏差,与生产力变化有关.
- 当应用到培训数据的生产率范围之外的文化时,模型可转移性在标位预测方面受到损害.
结论:
- 拉曼光谱是一种可行的工具,可以在细胞系发育过程中准确监测葡萄糖和乳酸盐.
- 使用拉曼光谱来准确预测标位,需要考虑特定的克隆特征.
- 克隆生产率显著影响了基于拉曼的标位预测模型的准确性和可转移性.
相关概念视频
01:39Test Cross
Alleles are different forms of the same gene. Humans and other diploid organisms inherit two alleles of every gene, one from each parent.
02:27Trihybrid Crosses
Trihybrid Crosses
Some of Mendel’s crosses examined three pairs of contrasting characteristics. Such a cross is called a trihybrid cross. A trihybrid cross is a combination of three individual monohybrid crosses. For example, plant height (tall vs. short), seed shape (round vs. wrinkled), and seed color (yellow vs. green).
The F1 generation plants of a trihybrid cross are heterozygous for all three traits and produce eight gametes. Upon self-fertilization, these gametes have an equal chance to...
Some of Mendel’s crosses examined three pairs of contrasting characteristics. Such a cross is called a trihybrid cross. A trihybrid cross is a combination of three individual monohybrid crosses. For example, plant height (tall vs. short), seed shape (round vs. wrinkled), and seed color (yellow vs. green).
The F1 generation plants of a trihybrid cross are heterozygous for all three traits and produce eight gametes. Upon self-fertilization, these gametes have an equal chance to...