相关实验视频
Updated: May 12, 2026
14:23
Recombineering Homologous Recombination Constructs in Drosophila
Published on: July 13, 2013
跨物种基因重新设计利用正义信息和生成建模
Manato Akiyama1, Motohiko Tashiro2, Ying Huang2
1Department of Data Science, Kitasato University School of Frontier Engineering, Sagamihara, Kanagawa, Japan.
Nature communications
|March 3, 2026
概括
人工智能模型OrthologTransformer通过学习进化适应来设计基因,优于传统的编码子优化以获得更好的蛋白质表达. 这种人工智能引导的基因设计提高了新宿主中的酶性能.
科学领域:
- 合成生物学 合成生物学
- 生物信息学是一种生物信息学.
- 机器学习 机器学习
背景情况:
- 传统的基因表达依赖于代优化,仅限于同义代替代.
- 自然进化的基因表现出更深层次的适应性变化,包括非同义突变和indels,用于宿主适应.
研究的目的:
- 介绍OrthologTransformer,这是一个深度学习模型,用于在物种之间转换正统基因.
- 开发一种方法来预测优化的编码序列,以保持标物种中的蛋白质功能.
主要方法:
- 使用基于变压器的深度学习架构.
- 在大规模的正统基因数据集上训练模型.
- 总结了诸如代码交换,氨基酸突变和indels等进化差异.
主要成果:
- 算法转换器的设计更像本地主机算法,而不是编码子优化的序列.
- 保护了蛋白质功能,并在各种细菌物种中实现了卓越的表达产量.
- 在 Bacillus subtilis 中,一个由 OrthologTransformer 重新设计的 PETase 显示出 ~ 10 倍高的活性和表达,而不是代码子优化的版本.
结论:
- 使用OrthologTransformer的人工智能引导的基因设计可以提高酶的性能和表达水平.
- 该模型有效地捕捉了进化适应,以改善异质基因表达.
- 展示了人工智能驱动的蛋白质工程和合成生物学应用的新方法.
相关概念视频
00:49What is Genetic Engineering?
Overview
01:16In-vitro Mutagenesis
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
02:31Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
02:08Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
02:08Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...