iSoMAs:在人类癌症中发现异型表达和体质突变关联
Hua Tan1, Valer Gotea1, Sushil K Jaiswal1
1Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS computational biology
|March 7, 2025
概括
在癌症中异常的替代拼接是由体质突变驱动的. 我们的新计算工具iSoMAs有效地将这些突变与异型水平的改变基因表达联系起来,揭示了关键的癌症相关基因.
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:
- 异常的替代拼接是癌症的标志,影响了扩散,血管生成和入侵.
- 体点突变通常会破坏拼接,通过改变功能途径促进癌细胞存活.
研究的目的:
- 开发一个高效的计算管道,iSoMAs (异形表达和体质突变协会),以分析体质突变对异形水平的转录组全基因表达的影响.
- 识别基因,其中体突变与多种癌症类型的异构体表达变化有显著关联.
主要方法:
- 开发iSoMAs,一个利用主要组件分析进行尺寸缩小的计算管道.
- 在癌症基因组图谱中的33种癌症类型中的9,738个瘤样本上应用iSoMAs.
- 湿实验室验证TP53突变与细胞周期基因差异性异型表达的关联.
主要成果:
- 确定了908个体质突变基因,与至少三种癌症类型的异型表达发生变化有显著关联.
- 发现突变通过cis和trans作用机制影响异型表达,涉及瘤基因,瘤抑制剂,RNA结合蛋白和拼接因子.
- 在细胞周期基因中验证了TP53突变和差异性异型表达之间的直接关联,并对其他已识别的基因进行了进一步的文献验证.
结论:
- iSoMAs提供了一种高效和计算可扩展的方法,用于研究癌症中突变驱动的异型表达变化.
- 这项研究揭示了调控因子,包括拼接因子和RNA结合蛋白,以及癌症中的转录格局之间的关键关联.
- 研究结果强调了替代拼接在癌症中的失调的重要性,并确定了用于治疗向的新型候选基因.
更多相关视频
11:15Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
24.3K
07:47Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
1.4K
相关概念视频
02:21Cancers Originate from Somatic Mutations in a Single Cell
11.4K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
11.4K
02:38The Ras Gene
6.1K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.1K
01:12Loss of Tumor Suppressor Gene Functions
4.7K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.7K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.3K
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...
7.3K
01:33Cancer-Critical Genes I: Proto-oncogenes
8.6K
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...
8.6K
01:20Mismatch Repair
4.7K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.7K