Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University Uttar Pradesh Noida-201313, India.
J Microbiol Biotechnol. 2022 Mar 28;32(3):365-377. doi: 10.4014/jmb.2108.08007.
Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with , , , , , , and as hub genes with high connectivity. for cervical cancer, for hepatic cirrhosis, for glioblastoma and for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.
哺乳动物雷帕霉素靶蛋白（mTOR）是细胞磷脂酰肌醇 3-激酶（PI3K）途径的丝氨酸-苏氨酸激酶成员，通过转录和翻译控制参与多种生物学功能。mTOR 是 PI3K/Akt 信号通路的下游介质，在细胞存活中发挥关键作用。在癌症中，该途径可以通过膜受体激活，包括 HER（或 ErbB）家族生长因子受体、胰岛素样生长因子受体和雌激素受体。在本工作中，我们使用自然语言处理汇集了基于数据组装的 mTORC1 电子网络，该网络由 470 条边（激活/相互作用和/或抑制）和 206 个节点组成，代表基因/蛋白质，使用 Cytoscape 3.6.0 编辑器及其插件进行分析。实验设计包括从基因表达综合数据库（NCBI GEO）中提取与五种不同类型的癌症（即胰腺导管腺癌、肝硬变、宫颈癌、胶质母细胞瘤和间变性甲状腺癌）相关的基因表达数据，然后使用 R 和 Bioconductor 对数据进行预处理和归一化。使用 ExprEssence 插件进行网络凝聚，以识别基因表达样本中差异表达的基因。进行基因本体论（GO）分析，以找出网络中过度表达的 GO 术语。此外，还对蛋白质-蛋白质相互作用（PPI）网络进行了途径富集和功能模块分析。我们的结果表明，NOTCH1、NOTCH3、FLCN、SOD1、SOD2、NF1 和 TLR4 是不同癌症类型中上调的蛋白质，突出了它们在癌症进展中的作用。MCODE 分析确定了每种癌症类型的基因簇，其中 、 、 、 、 和 是具有高连通性的枢纽基因。对于宫颈癌， 对于肝硬变， 对于胶质母细胞瘤和 对于间变性甲状腺癌，通过生存分析确定了具有预后意义的基因。
