一种连续的表现模型,用于预测基因表达和环境的组合变异给定的生长率
Ryan M Otto1, Agata Turska-Nowak2, Philip M Brown1
1Green Center for Systems Biology - Lyda Hill Department of Bioinformatics, The University of Texas Southwestern Medical Center, Dallas, TX 75230, USA.
Cell systems
|February 10, 2024
概括
由于基因相互作用,预测细菌生长率是复杂的. 这项研究使用机器学习来绘制基因表达和生长的地图,成功地建模复杂的遗传效应以获得更好的预测.
科学领域:
- 微生物学 微生物学
- 系统生物学 系统生物学
- 计算生物学 计算生物学
背景情况:
- 由于复杂的基因相互作用 (表观) 和环境因素,预测细菌生长率表型具有挑战性.
- 了解基因表达变异如何影响生长对于各种生物和生物技术应用至关重要.
研究的目的:
- 开发和验证一种可解释的机器学习方法,用于绘制基因表达-增长率格局的地图.
- 在各种环境条件下量化细菌基因表达中的表现性相互作用.
主要方法:
- 利用不匹配的CRISPR干扰 (CRISPRi) 在大肠杆菌中产生超过8,000个定位的基因表达变化.
- 应用了一个可解释的机器学习模型,整合了多达22个不同的环境中的稀少样本实验数据.
- 探索双重和三重基因扰动,以评估对生长率的表观性影响.
主要成果:
- 以前用于药物相互作用的双对相互作用模型有效地描述了基因表达-增长率数据.
- 该模型提供了反映路径架构的可解释参数,并成功预测了多达四个基因扰动的综合效应.
- 在单独对双扰动数据进行训练时,证明了模型的概括能力.
结论:
- 开发的机器学习方法准确地模拟了受基因表达和环境环境影响的细菌生长率表型.
- 这种方法为了解细菌基因表达约束和优化生长条件提供了强大的工具.
- 该方法在药物基因组学和合成生物学等领域具有广泛的适用性.
相关概念视频
Gene-Environment Interactions
318
Gene expression is a dynamic process that is significantly influenced by environmental factors. This interaction underlies the complex nature of biological development and the phenotypic differences observed among individuals, even among those with identical genetic makeups. Factors such as radiation, temperature, behavior, nutrition, and stress play pivotal roles in determining how genes are expressed. The concept of the reaction range is central to understanding this interaction. It posits...
318
Epistasis Analysis
5.0K
Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
5.0K
Epistasis
46.8K
In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
46.8K
Combinatorial Gene Control
8.3K
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...
8.3K
Background and Environment Affect Phenotype
6.5K
Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
6.5K
Structure of a Gene
12.6K
A gene is the fundamental unit of heredity. Every individual has two copies of each gene, one inherited from each parent. Although most people contain the same genes, there is a small fraction that is slightly different amongst people. A gene with a small difference in its sequence of DNA bases forms different alleles, contributing to different phenotypes.
However, only 1% of the DNA is composed of genes that encode proteins; the rest, 99% is non-coding DNA. This non-coding DNA performs...
However, only 1% of the DNA is composed of genes that encode proteins; the rest, 99% is non-coding DNA. This non-coding DNA performs...
12.6K


