合成增强剂的细胞类型定向设计
Ibrahim I Taskiran1,2,3, Katina I Spanier1,2,3, Hannah Dickmänken1,2,3
1Laboratory of Computational Biology, VIB Center for AI & Computational Biology (VIB.AI), Leuven, Belgium.
Nature
|December 12, 2023
概括
深度学习模型可以为特定的细胞类型设计合成增强剂. 这种方法解码增强剂序列,使得果和人类的基因表达得到精确控制.
科学领域:
- 遗传学
- 计算生物学
- 分子生物学
背景情况:
- 转录增强剂通过结合转录因子来调节基因表达.
- 解码精确的监管逻辑和基于序列的增强剂是一个重大挑战.
研究的目的:
- 展示深度学习在设计合成细胞类型特异增强剂方面的能力.
- 研究增强剂的单核酸分辨率特征及其监管代码.
主要方法:
- 使用深度学习模型从随机序列设计合成增强剂.
- 对特定细胞类型 (肯昂细胞,质细胞) 的转基因果 (Drosophila) 大脑评估增强剂功能.
- 在增强剂序列中分析转录因子激活剂和抑制剂动机.
主要成果:
- 在Drosophila成功设计的功能性,细胞类型特定的合成增强剂.
- 创建了针对两种细胞类型的双代码增强剂和50个基对以下的最小增强剂.
- 基于动图强度,组合和排列的识别增强器代码.
- 使用类似原则成功设计人类增强剂.
结论:
- 深度学习为设计合成增强剂提供了一种有效的方法.
- 增强器的设计揭示了控制时间空间基因表达的规范性代码.
- 已识别的增强剂代码在各个物种中保存,并可用于细胞状态操纵.
相关概念视频
Conservative Site-specific Recombination and Phase Variation
6.0K
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...
6.0K
Synthetic Biology
4.8K
Synthetic biology is an interdisciplinary science that involves using principles from disciplines such as engineering, molecular biology, cell biology, and systems biology. It involves remodeling existing organisms from nature or constructing completely new synthetic organisms for applications such as protein or enzyme production, bioremediation, value-added macromolecule production, and the addition of desirable traits to crops, to name a few.
Golden rice
Golden rice is a genetically modified...
Golden rice
Golden rice is a genetically modified...
4.8K
RNA Polymerase II Accessory Proteins
9.2K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.2K
Combinatorial Gene Control
8.4K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.4K


