生物信息学对mTOR信号通路的方法 - 关联基因和癌症病原发生的基因
Kursat Ozdilli1,2, Gozde Oztan3, Demet Kıvanç3
1Department of Medical Biology, Faculty of Medicine, Istanbul Medipol University, 34810 Istanbul, Turkey.
Genes
|November 27, 2025
概括
这项研究引入了癌症研究的可重复框架,确定了关键的mTOR通路基因,并优先考虑了生物标志物验证的候选人. 该方法整合了基因组学和网络分析,以发现共享的驱动因素和瘤特定节点.
科学领域:
- 在瘤学瘤学.
- 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:
- 拉巴素 (mTOR) 激酶的机械标对细胞生长和新陈代谢至关重要,其失调与癌症有关.
- 目前的路径治愈方法在识别mTOR轴的可操作生物标志物方面存在局限性.
- 需要一个网络意识的,可重复的框架来整合多omics数据,以便全面发现生物标志物.
研究的目的:
- 开发和验证一种泛癌,网络意识的框架,用于识别mTOR路径生物标志物.
- 将广泛共享的驱动程序与mTOR网络中的瘤特定节点区分开来.
- 为生物标志物验证优先考虑非突变的近邻网络候选物.
主要方法:
- 从多个数据库 (GeneCards,KEGG,STRING,UniProt,PathCards) 收集并协调了mTOR相关的基因和相互作用.
- 开发了一个将基因型与路径架构,表达式重新连接和表型联系起来的模型.
- 应用了泛癌变异映射,基于表达的活动评分和拓意识的网络传播 (PageRank,随机步行与重启).
主要成果:
- 确定了mTOR信号传递和氨基酸反应通路的显著丰富.
- 在mTOR和其合作伙伴 (例如,TSC2,RICTOR) 之间在癌症中确定的疾病关联.
- 基于网络近距离和活动签名的区别共享驱动程序 (例如,PTEN,PIK3CA) 来自以血统丰富的节点和优先级的新候选程序.
结论:
- 开发的框架提供了一种透明,可重复的方法,用于统一策划生物学,基因组学和网络拓学,用于mTOR轴研究.
- 该方法通过优先考虑非突变,拓推断的候选人,并区分共享与瘤特异性驱动因素来完善生物标志物发现.
- 该框架支持对优先级候选者的验证,并设计关联性研究,将途径活性与临床反应联系起来.
更多相关视频
相关概念视频
03:03mTOR Signaling and Cancer Progression
4.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.6K
01:22PI3K/mTOR/AKT Signaling Pathway
5.3K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.3K
01:33Cancer-Critical Genes I: Proto-oncogenes
11.1K
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...
11.1K
01:19Interactions Between Signaling Pathways
7.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.2K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
9.3K
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...
9.3K
02:54Canonical Wnt Signaling Pathway
10.4K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.4K