通过合预测和生成模型对大肠杆菌进行智能设计
Jie Li1, Lin-Feng Wu1, Kai Liu1
1Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China.
ACS synthetic biology
|September 4, 2025
概括
这项研究开发了用于预测和生成细菌转录终止器的计算模型,这对于合成生物学基因电路设计至关重要. 这些模型准确地预测了终结器的强度,并产生了高终结效率的新序列.
科学领域:
- 合成生物学
- 分子生物学
- 计算生物学
背景情况:
- 转录终止器是基因电路设计的基本遗传调节元素.
- 对于精确的基因电路工程来说, 终结器强度的准确描述至关重要.
- 目前用于终结器强度预测的计算方法由于序列和热力学特征集成不足而受到限制.
研究的目的:
- 为大肠杆菌终结者开发智能设计方法.
- 构建一个强大的终结器强度预测模型,包含序列和热力学特征.
- 使用深度生成模型生成新的终结器序列,用于增强基因电路应用.
主要方法:
- 从大肠杆菌内在终结体中提取了序列和热力学特征.
- 开发了用于终结器强度预测的机器学习模型,实现R2=0.72.
- 使用生成对抗网络 (GAN) 来学习和生成新的终结器序列.
主要成果:
- 机器学习模型表现出强大的终结器强度预测性能.
- 使用GAN生成的终结器序列显示了与内在终结器相似的数据分布,验证了它们的可靠性.
- 实验验证证了72%的选定产生的终止器表现出超过90%的终止效率.
结论:
- 该研究成功构建了终结体强度预测模型和终结体生成模型.
- 这些模型为合成生物学基因电路的终结器设计提供了必要的支持.
- 开发的智能设计方法增强了生物组件的模块化性,并推进了合成生物学.
相关概念视频
Transcription Attenuation in Prokaryotes
16.0K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
16.0K
Mismatch Repair
5.2K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.2K
Improving Translational Accuracy
11.8K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
11.8K
Termination of Translation
25.7K
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
25.7K
Next-generation Sequencing
92.5K
The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....
92.5K


