ceQTL:一种共同表达的QTL模型,用于检测影响转录因子结合及其目标调节的变异
bioRxiv : the preprint server for biology
|November 24, 2025
概括
我们开发了一种新方法,差异性共表达QTL (ceQTL),以确定基因组变异 (SNP) 如何通过转录因子 (TF) 结合影响基因表达,从而为遗传变异提供更深入的生物学见解.
科学领域:
- 基因组学就是基因组学.
- 系统生物学 系统生物学
- 生物信息学是一种生物信息学.
背景情况:
- 表达量的特征位置 (eQTL) 映射将基因组变异与基因表达联系起来,但往往缺乏机械洞察力.
- 现有的方法很难正式证明eQTL是否由转录因子 (TF) 结合介导.
- 了解单核酸多态 (SNP) 对基因调节的功能影响对于疾病研究至关重要.
研究的目的:
- 引入一种新的统计方法,即微分共表达QTL (ceQTL),用于检测由TF活动调制的eQTL.
- 为研究TF结合在SNP介导的基因表达变化中的作用提供数据驱动的方法.
- 加强eQTL协会的生物学解释,并揭示潜在的监管机制.
主要方法:
- 开发了使用Chow统计数据的ceQTL模型,以评估TF,目标基因 (TG) 和SNP之间的差异相关性.
- 将ceQTL模型应用于仿真数据集和来自基因型-组织表达 (GTEx) 项目的肺组织数据.
- 集成的TF结合亲缘关系分析,为已识别的ceQTL提供额外的功能证据.
主要成果:
- 在模拟 (AUC) 中,ceQTL模型在各种样本大小和小等位基因频率中检测真实ceQTL的稳定性得到了证明.
- 对GTEx肺组织数据的分析揭示了具有强烈ceQTL信号的eQTL子集,表明通过TF结合通过SNP介导的基因表达变化.
- 确定了传统eQTL分析可能忽略的ceQTL,突出了该方法发现新型监管关系的能力.
结论:
- ceQTL分析为理解eQTL机制提供了一个更易于解释的框架,特别是涉及TF约束.
- 开发的方法为基因组变异如何影响基因表达和潜在的疾病表型提供了宝贵的生物学见解.
- 这种方法通过提供一种正式的统计方法来将SNP,TF和基因表达联系起来,从而推动了该领域的发展.
相关概念视频
02:13Cooperative Binding of Transcription Regulators
7.1K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.1K
02:13Cooperative Binding of Transcription Regulators
2.4K
2.4K
02:16Transcription Factors
82.2K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.2K
01:30General Transcription Factors
6.7K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
6.7K
01:23Regulation of Expression at Multiple Steps
1.3K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.3K
02:04Co-activators and Co-repressors
8.4K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.4K