监管网络的灵活建模可以改善转录因子活动估计
Chen Chen1,2, Megha Padi3,4
1Department of Epidemiology and Biostatistics, University of Arizona Mel and Enid Zuckerman College of Public Health, Tucson, AZ, USA.
NPJ systems biology and applications
|May 28, 2024
概括
这项研究引入了TIGER,这是一种用于从基因表达数据中推断转录因子 (TF) 活性的新算法. 泰格准确地模拟特定环境调节,在预测TF在细胞过程和疾病中的作用方面表现优于现有的方法.
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:
- 转录调节对于细胞命运和疾病至关重要.
- 目前用于估计转录因子 (TF) 活性的方法缺乏适应性,以适应不同细胞类型和条件的动态调控变化.
- 从基因表达数据中推断关键调节者是一个重大挑战.
研究的目的:
- 开发一种新的算法,使用基因表达和监管数据 (TIGER) 的转录推理,以克服现有的TF活动估计方法的局限性.
- 实现TF激活和抑制事件的灵活建模,并同时估计TF活动水平和监管网络变化.
- 提高TF活动推断在各种生物环境中的准确性和适应性.
主要方法:
- 开发了TIGER算法,结合了稀疏的贝叶斯算法,先加重必要的监管边缘,并缩小不相关的边缘.
- 在监管网络中灵活模拟激活和抑制事件.
- 同时估计转录因子活性水平和底层监管网络的动态变化.
- 将TIGER应用于酵母和癌症TF淘汰数据集,以及特定于组织和细胞类型的RNA-seq数据.
主要成果:
- 与酵母和癌症TF淘汰数据集的可比方法相比,TIGER显示出更高的预测准确性.
- 该算法在应用于细胞类型特定的RNA-seq数据时,成功地发现了调节机制的差异.
- TIGER有效地模拟特定环境的法规,以便更准确地推断TF活动.
结论:
- TIGER提供了一种强大而可适应的方法,通过模拟特定环境调节来推断转录因子活动.
- 这些发现强调了考虑不同细胞环境中的动态调节机制的重要性.
- 这项工作强调了TIGER在促进我们对健康和疾病中转录调节的理解方面的实用性.
相关概念视频
02:33Combinatorial 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
02:13Cooperative Binding of Transcription Regulators
6.4K
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...
6.4K
02:23Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
02:36RNA 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
02:04Co-activators and Co-repressors
7.3K
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...
7.3K
02:16Transcription Factors
75.8K
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...
75.8K