一种计算方法来证明通过染色体访问在结直肠癌中控制基因表达的方法
Caleb J Pecka1, Ishwor Thapa1, Amar Singh2
1College of IS&T, University of Nebraska at Omaha, Omaha, NE, United States of America.
Research square
|July 3, 2023
概括
这项研究提出了一个新的计算工具来分析DNA可访问性,转录因子结合和突变如何影响结直肠癌中的基因表达的变化. 该工具揭示了驱动结肠癌进展的关键转录因子相互作用.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 生物信息学是一种生物信息学.
背景情况:
- 染色体可访问性测序的进步,如ATAC-seq,提高了对癌症等疾病中的基因调节的理解.
- 大肠直肠癌 (CRC) 的发病包括复杂的基因调节变化.
研究的目的:
- 引入一种可复制的计算工具,用于分析染色质可访问性,转录因子 (TF) 结合,TF突变和CRC中的基因表达之间的联系.
- 利用公共数据调查TF突变和可访问性对CRC基因表达的影响.
主要方法:
- 使用工作流管理系统开发和包装生物信息管道.
- 对公开可用的结直肠癌ATAC-seq和基因表达数据的分析.
- 定量化染色质可访问性,TF结合,TF突变和基因表达之间的关系.
主要成果:
- 建立了染色体可访问性和基因表达之间的明确联系,突出了TF基因中单核酸多态 (SNP) 突变的作用.
- 在结肠癌患者中发现了关键TF相互作用的显著上调.
- 证明了TF相互作用,促进了亡调节 (E2F1,MYC,MYCN) 和BCL-2蛋白家族激活 (TP73).
结论:
- 开发的计算工具使得CRC中基因调节的可重复分析成为可能.
- 染色体可访问性,TF结合和TF突变是结肠癌中基因表达的关键决定因素.
- 特定的TF相互作用在结肠癌中显著改变,提供潜在的治疗点.
相关概念视频
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
Epigenetic Regulation
3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.1K
Chromatin Position Affects Gene Expression
23.4K
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
23.4K
Cancer-Critical Genes II: Tumor Suppressor Genes
7.5K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.5K
Reporter Genes
11.6K
Reporter genes are a type of protein-coding gene that are often tagged to a gene of interest. Once inside a target cell, reporter genes usually produce visually identifiable characteristics like fluorescence and luminescence when expressed along with the gene of interest. Thus, reporter genes “report” the presence or absence of genes of interest in an organism, determine the gene expression pattern, or track the physical location of a DNA segment or protein in the cell.
11.6K
Cancer-Critical Genes I: Proto-oncogenes
9.0K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.0K


