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siRNAEfficacyDB: An experimentally supported small interfering RNA efficacy database. siRNAEfficacyDB: 经实验支持的小干扰 RNA 药效数据库。
IF 1.9 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-11-14 DOI: 10.1049/syb2.12102
Yang Zhang, Ting Yang, Yu Yang, Dongsheng Xu, Yucheng Hu, Shuo Zhang, Nanchao Luo, Lin Ning, Liping Ren

Small interfering RNA (siRNA) has revolutionised biomedical research and drug development through precise post-transcriptional gene silencing technology. Despite its immense potential, siRNA therapy still faces technical challenges, such as delivery efficiency, targeting specificity, and molecular stability. To address these challenges and facilitate siRNA drug development, we have developed siRNAEfficacyDB, a comprehensive database that integrates experimentally validated siRNA efficacy data. This database contains 3544 siRNA records, covering 42 target genes and 5 cell lines. It provides detailed information on siRNA sequences, target genes, inhibition efficiencies, experimental techniques, cell lines, siRNA concentrations, and incubation times. siRNAEfficacyDB offers a user-friendly web interface that makes it easy to query, browse and analyse data, enabling efficient access to siRNA-related information. In summary, siRNAEfficacyDB provides a useful data foundation for siRNA drug design and optimisation, serving as a valuable resource for advancing computer-aided siRNA design research and nucleic acid drug development. siRNAEfficacyDB is freely available at https://cellknowledge.com.cn/siRNAEfficacy for non-commercial use.

通过精确的转录后基因沉默技术,小干扰 RNA(siRNA)为生物医学研究和药物开发带来了革命性的变化。尽管 siRNA 潜力巨大,但其治疗仍面临着技术挑战,如传递效率、靶向特异性和分子稳定性。为了应对这些挑战,促进 siRNA 药物开发,我们开发了 siRNAEfficacyDB,这是一个整合了经实验验证的 siRNA 疗效数据的综合数据库。该数据库包含 3544 条 siRNA 记录,涵盖 42 个靶基因和 5 个细胞系。siRNAEfficacyDB 提供用户友好的网络界面,便于查询、浏览和分析数据,使人们能够高效地获取 siRNA 相关信息。总之,siRNAEfficacyDB 为 siRNA 药物设计和优化提供了有用的数据基础,是推进计算机辅助 siRNA 设计研究和核酸药物开发的宝贵资源。siRNAEfficacyDB 可在 https://cellknowledge.com.cn/siRNAEfficacy 免费获取,但不得用于商业用途。
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引用次数: 0
Deep-GB: A novel deep learning model for globular protein prediction using CNN-BiLSTM architecture and enhanced PSSM with trisection strategy. Deep-GB:利用 CNN-BiLSTM 架构和增强型 PSSM(采用三分割策略)进行球状蛋白质预测的新型深度学习模型。
IF 1.9 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-11-08 DOI: 10.1049/syb2.12108
Sonia Zouari, Farman Ali, Atef Masmoudi, Sarah Abu Ghazalah, Wajdi Alghamdi, Faris A Kateb, Nouf Ibrahim

Globular proteins (GPs) play vital roles in a wide range of biological processes, encompassing enzymatic catalysis and immune responses. Enzymes, among these globular proteins, facilitate biochemical reactions, while others, such as haemoglobin, contribute to essential physiological functions such as oxygen transport. Given the importance of these considerations, accurately identifying Globular proteins is essential. To address the need for precise GP identification, this research introduces an innovative approach that employs a hybrid-based deep learning model called Deep-GP. We generated two datasets based on primary sequences and developed a novel feature descriptor called, Consensus Sequence-based Trisection-Position Specific Scoring Matrix (CST-PSSM). The model training phase involved the application of deep learning techniques, including the bidirectional long short-term memory network (BiLSTM), gated recurrent unit (GRU), and convolutional neural network (CNN). The BiLSTM and CNN were hybridised for ensemble learning. The CST-PSSM-based ensemble model achieved the most accurate predictive outcomes, outperforming other competitive predictors across both training and testing datasets. This demonstrates the potential of harnessing deep learning for precise GB prediction as a robust tool to expedite research, streamline drug discovery, and unveil novel therapeutic targets.

球蛋白(GPs)在广泛的生物过程中发挥着重要作用,包括酶催化和免疫反应。这些球蛋白中的酶促进生化反应,而血红蛋白等其他球蛋白则有助于氧气运输等基本生理功能。鉴于这些因素的重要性,准确鉴定球蛋白至关重要。为了满足精确识别球蛋白的需求,本研究引入了一种创新方法,该方法采用了一种名为 Deep-GP 的混合型深度学习模型。我们基于主序列生成了两个数据集,并开发了一种名为 "基于共识序列的三剖面位置特异性评分矩阵(CST-PSSM)"的新型特征描述符。模型训练阶段涉及深度学习技术的应用,包括双向长短期记忆网络(BiLSTM)、门控递归单元(GRU)和卷积神经网络(CNN)。BiLSTM 和 CNN 被混合用于集合学习。基于 CST-PSSM 的集合模型取得了最准确的预测结果,在训练和测试数据集上都优于其他有竞争力的预测器。这证明了利用深度学习进行精确国标预测的潜力,它是加快研究、简化药物发现和揭示新型治疗靶点的有力工具。
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引用次数: 0
Developing a machine learning model with enhanced performance for predicting COVID-19 from patients presenting to the emergency room with acute respiratory symptoms. 开发一种性能更强的机器学习模型,用于预测急诊室急性呼吸道症状患者的 COVID-19。
IF 1.9 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-10-29 DOI: 10.1049/syb2.12101
Maha Mesfer Alghamdi, Naael H Alazwary, Waleed A Alsowayan, Mohmmed Algamdi, Ahmed F Alohali, Mustafa A Yasawy, Abeer M Alghamdi, Abdullah M Alassaf, Mohammed R Alshehri, Hussein A Aljaziri, Nujoud H Almoqati, Shatha S Alghamdi, Norah A Bin Magbel, Tareq A AlMazeedi, Nashaat K Neyazi, Mona M Alghamdi, Mohammed N Alazwary

Artificial Intelligence is playing a crucial role in healthcare by enhancing decision-making and data analysis, particularly during the COVID-19 pandemic. This virus affects individuals across all age groups, but its impact is more severe on the elderly and those with underlying health issues like chronic diseases. This study aimed to develop a machine learning model to improve the prediction of COVID-19 in patients with acute respiratory symptoms. Data from 915 patients in two hospitals in Saudi Arabia were used, categorized into four groups based on chronic lung conditions and COVID-19 status. Four supervised machine learning algorithms-Random Forest, Bagging classifier, Decision Tree, and Logistic Regression-were employed to predict COVID-19. Feature selection identified 12 key variables for prediction, including CXR abnormalities, smoking status, and WBC count. The Random Forest model showed the highest accuracy at 99.07%, followed by Decision Tree, Bagging classifier, and Logistic Regression. The study concluded that machine learning algorithms, particularly Random Forest, can effectively predict and classify COVID-19 cases, supporting the development of computer-assisted diagnostic tools in healthcare.

人工智能通过加强决策和数据分析,在医疗保健领域发挥着至关重要的作用,尤其是在 COVID-19 大流行期间。这种病毒对所有年龄段的人都有影响,但对老年人和有慢性病等潜在健康问题的人的影响更为严重。本研究旨在开发一种机器学习模型,以提高对急性呼吸道症状患者感染 COVID-19 的预测能力。研究使用了沙特阿拉伯两家医院 915 名患者的数据,根据慢性肺部疾病和 COVID-19 状态分为四组。研究人员采用了四种有监督的机器学习算法--随机森林(Random Forest)、袋式分类器(Bagging classifier)、决策树(Decision Tree)和逻辑回归(Logistic Regression)来预测 COVID-19。特征选择确定了 12 个关键预测变量,包括 CXR 异常、吸烟状况和白细胞计数。随机森林模型的准确率最高,达到 99.07%,其次是决策树、袋式分类器和逻辑回归。研究认为,机器学习算法,尤其是随机森林算法,可以有效地对 COVID-19 病例进行预测和分类,为医疗保健领域计算机辅助诊断工具的开发提供了支持。
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引用次数: 0
Mechanism of action of "cistanche deserticola-Polygala" in treating Alzheimer's disease based on network pharmacology methods and molecular docking analysis. 基于网络药理学方法和分子对接分析的 "肉苁蓉-保利加 "治疗阿尔茨海默病的作用机制。
IF 1.9 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-10-11 DOI: 10.1049/syb2.12100
Shaoqiang Wang, Yifan Wang

This article used network pharmacology, molecular docking, GEO analysis, and Gene Set Enrichment Analysis to obtain 38 main chemical components and 66 corresponding targets involved in Alzheimer's disease (AD) treatment in "Cistanche deserticola-Polygala". Through further Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analysis, we obtained AD signalling pathways, calcium signalling pathways, and other signalling pathways related to the treatment of AD with "Cistanche deserticola-Polygala". Molecular docking showed that most of the core chemical components had good binding ability with the core targets. This article aims to reveal the mechanism of "Cistanche deserticola-Polygala" in treating AD and provide a basis for the treatment of AD with "Cistanche deserticola-Polygala".

本文利用网络药理学、分子对接、GEO分析和基因组富集分析等方法,获得了 "肉苁蓉-保力加 "中参与阿尔茨海默病(AD)治疗的38种主要化学成分和66个相应靶点。通过进一步的基因本体和京都基因组百科全书富集分析,我们获得了与 "肉苁蓉-多糖 "治疗阿尔茨海默病(AD)相关的AD信号通路、钙信号通路和其他信号通路。分子对接表明,大部分核心化学成分与核心靶标具有良好的结合能力。本文旨在揭示 "肉苁蓉多糖 "治疗AD的机制,为 "肉苁蓉多糖 "治疗AD提供依据。
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引用次数: 0
Comprehensive transcriptome and scRNA-seq analyses uncover the expression and underlying mechanism of SYNJ2 in papillary thyroid carcinoma 全面的转录组和 scRNA-seq 分析揭示了 SYNJ2 在甲状腺乳头状癌中的表达及其潜在机制。
IF 1.9 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-10-06 DOI: 10.1049/syb2.12099
Yuan-Ping Yang, Zhi-Guang Huang, Jia-Yuan Luo, Juan He, Lin Shi, Gang Chen, Si-Yuan Chen, Yu-Wen Deng, Yi-Jia Yang, Yi-Jun Tang, Yu-Yan Pang

Synaptojanin 2 (SYNJ2) has crucial role in various tumors, but its role in papillary thyroid carcinoma (PTC) remains unexplored. This study first detected SYNJ2 protein expression in PTC using immunohistochemistry method and further assessed SYNJ2 mRNA expression through mRNA chip and RNA sequencing data and its association with clinical characteristics. Additionally, KEGG, GSVA, and GSEA analyses were conducted to investigate potential biological functions, while single-cell RNA sequencing data were used to explore SYNJ2's underlying mechanisms in PTC. Meanwhile, immune infiltration status in different SYNJ2 expression groups were analyzed. Besides, we investigated the immune checkpoint gene expression and implemented drug sensitivity analysis. Results indicated that SYNJ2 is highly expressed in PTC (SMD = 0.66 [95% CI: 0.17–1.15]) and could distinguish between PTC and non-PTC tissues (AUC = 0.74 [0.70–0.78]). Furthermore, the study identified 134 intersecting genes of DEGs and CEGs, mainly enriched in the angiogenesis and epithelial-mesenchymal transition (EMT) pathways. Subsequent analysis showed the above pathways were activated in PTC epithelial cells. PTC patients with high SYNJ2 expression showed higher sensitivity to the six common drugs. Summarily, SYNJ2 may promote PTC progression through angiogenesis and EMT pathways. High SYNJ2 expression is associated with better response to immunotherapy and chemotherapy.

突触素2(Synaptojanin 2,SYNJ2)在多种肿瘤中发挥着重要作用,但其在甲状腺乳头状癌(PTC)中的作用仍有待探索。本研究首先利用免疫组化方法检测了SYNJ2蛋白在PTC中的表达,并通过mRNA芯片和RNA测序数据进一步评估了SYNJ2 mRNA的表达及其与临床特征的关系。此外,研究人员还通过KEGG、GSVA和GSEA分析研究了SYNJ2的潜在生物学功能,并利用单细胞RNA测序数据探讨了SYNJ2在PTC中的潜在机制。同时,分析了不同SYNJ2表达组的免疫浸润状况。此外,我们还研究了免疫检查点基因的表达,并进行了药物敏感性分析。结果表明,SYNJ2 在 PTC 中高表达(SMD = 0.66 [95% CI: 0.17-1.15]),并能区分 PTC 和非 PTC 组织(AUC = 0.74 [0.70-0.78])。此外,研究还发现了 134 个 DEGs 和 CEGs 交叉基因,主要集中在血管生成和上皮-间质转化(EMT)通路。随后的分析表明,上述通路在 PTC 上皮细胞中被激活。SYNJ2高表达的PTC患者对六种常见药物的敏感性更高。综上所述,SYNJ2可能通过血管生成和EMT途径促进PTC的进展。SYNJ2的高表达与对免疫疗法和化疗的更好反应相关。
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引用次数: 0
iGATTLDA: Integrative graph attention and transformer-based model for predicting lncRNA-Disease associations iGATTLDA:基于图注意和转换器的整合模型,用于预测 lncRNA 与疾病的关联。
IF 1.9 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-09-22 DOI: 10.1049/syb2.12098
Biffon Manyura Momanyi, Sebu Aboma Temesgen, Tian-Yu Wang, Hui Gao, Ru Gao, Hua Tang, Li-Xia Tang

Long non-coding RNAs (lncRNAs) have emerged as significant contributors to the regulation of various biological processes, and their dysregulation has been linked to a variety of human disorders. Accurate prediction of potential correlations between lncRNAs and diseases is crucial for advancing disease diagnostics and treatment procedures. The authors introduced a novel computational method, iGATTLDA, for the prediction of lncRNA-disease associations. The model utilised lncRNA and disease similarity matrices, with known associations represented in an adjacency matrix. A heterogeneous network was constructed, dissecting lncRNAs and diseases as nodes and their associations as edges. The Graph Attention Network (GAT) is employed to process initial features and corresponding adjacency information. GAT identified significant neighbouring nodes in the network, capturing intricate relationships between lncRNAs and diseases, and generating new feature representations. Subsequently, the transformer captures global dependencies and interactions across the entire sequence of features produced by the GAT. Consequently, iGATTLDA successfully captures complex relationships and interactions that conventional approaches may overlook. In evaluating iGATTLDA, it attained an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95 and an area under the precision recall curve (AUPRC) of 0.96 with a two-layer multilayer perceptron (MLP) classifier. These results were notably higher compared to the majority of previously proposed models, further substantiating the model’s efficiency in predicting potential lncRNA-disease associations by incorporating both local and global interactions. The implementation details can be obtained from https://github.com/momanyibiffon/iGATTLDA.

长非编码 RNA(lncRNA)已成为调控各种生物过程的重要因素,它们的失调与多种人类疾病有关。准确预测lncRNA与疾病之间的潜在相关性对于推进疾病诊断和治疗程序至关重要。作者介绍了一种新的计算方法--iGATTLDA,用于预测lncRNA与疾病的关联。该模型利用 lncRNA 和疾病的相似性矩阵,并用邻接矩阵表示已知的关联。将 lncRNA 和疾病作为节点,将它们之间的关联作为边,构建了一个异构网络。采用图形注意网络(GAT)处理初始特征和相应的邻接信息。GAT 识别网络中重要的邻接节点,捕捉 lncRNA 与疾病之间错综复杂的关系,并生成新的特征表征。随后,转换器捕捉由 GAT 生成的整个特征序列中的全局依赖关系和相互作用。因此,iGATTLDA 成功捕捉到了传统方法可能忽略的复杂关系和相互作用。在对 iGATTLDA 进行评估时,通过使用双层多层感知器(MLP)分类器,它的接收器操作特征曲线(ROC)下面积(AUC)达到了 0.95,精确召回曲线(AUPRC)下面积(AUC)达到了 0.96。与之前提出的大多数模型相比,这些结果明显更高,进一步证实了该模型通过结合局部和全局相互作用预测潜在lncRNA-疾病关联的效率。具体实现细节请访问 https://github.com/momanyibiffon/iGATTLDA。
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引用次数: 0
A tumour-associated macrophage-based signature for deciphering prognosis and immunotherapy response in prostate cancer 基于肿瘤相关巨噬细胞的特征,用于解读前列腺癌的预后和免疫疗法反应。
IF 1.9 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-08-13 DOI: 10.1049/syb2.12097
Jian Wang, Tao Guo, Yuanyuan Mi, Xiangyu Meng, Shuang Xu, Feng Dai, Chengwen Sun, Yi Huang, Jun Wang, Lijie Zhu, Jianquan Hou, Sheng Wu

For the multistage progression of prostate cancer (PCa) and resistance to immunotherapy, tumour-associated macrophage is an essential contributor. Although immunotherapy is an important and promising treatment modality for cancer, most patients with PCa are not responsive towards it. In addition to exploring new therapeutic targets, it is imperative to identify highly immunotherapy-sensitive individuals. This research aimed to establish a signature risk model, which derived from the macrophage, to assess immunotherapeutic responses and predict prognosis. Data from the UCSC-XENA, GEO and TISCH databases were extracted for analysis. Based on both single-cell datasets and bulk transcriptome profiles, a macrophage-related score (MRS) consisting of the 10-gene panel was constructed using the gene set variation analysis. MRS was highly correlated with hypoxia, angiogenesis, and epithelial-mesenchymal transition, suggesting its potential as a risk indicator. Moreover, poor immunotherapy responses and worse prognostic performance were observed in the high-MRS group of various immunotherapy cohorts. Additionally, APOE, one of the constituent genes of the MRS, affected the polarisation of macrophages. In particular, the reduced level of M2 macrophage and tumour progression suppression were observed in PCa xenografts which implanted in Apolipoprotein E-knockout mice. The constructed MRS has the potential as a robust prognostic prediction tool, and can aid in the treatment selection of PCa, especially immunotherapy options.

前列腺癌(PCa)的多期进展和对免疫疗法的抵抗,肿瘤相关巨噬细胞是一个重要因素。尽管免疫疗法是一种重要且前景广阔的癌症治疗方式,但大多数前列腺癌患者对免疫疗法并不敏感。除了探索新的治疗靶点,当务之急是确定对免疫疗法高度敏感的个体。这项研究旨在建立一个源自巨噬细胞的特征风险模型,以评估免疫治疗反应并预测预后。研究人员从 UCSC-XENA、GEO 和 TISCH 数据库中提取数据进行分析。基于单细胞数据集和大容量转录组图谱,利用基因组变异分析构建了由10个基因组成的巨噬细胞相关评分(MRS)。MRS与缺氧、血管生成和上皮-间质转化高度相关,表明其具有作为风险指标的潜力。此外,在各种免疫疗法队列中观察到,高MRS组的免疫疗法反应较差,预后表现较差。此外,MRS的组成基因之一APOE也影响了巨噬细胞的极化。特别是在植入载脂蛋白E基因敲除小鼠体内的PCa异种移植物中观察到了M2巨噬细胞水平的降低和肿瘤进展的抑制。构建的MRS有可能成为一种可靠的预后预测工具,并有助于选择PCa的治疗方法,尤其是免疫疗法。
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引用次数: 0
Identification and analysis of epithelial-mesenchymal transition-related key long non-coding RNAs in hypospadias 尿道下裂中上皮-间质转化相关关键长非编码 RNA 的鉴定与分析
IF 1.9 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-07-25 DOI: 10.1049/syb2.12096
Hongjie Gao, Chen Ding, Mengmeng Chang, Zhiyi Lu, Ding Li, Dan Bi, Fengyin Sun

EMT dysfunction is a dominant mechanisms of hypospadias. Thus, identification of EMT-related lncRNAs based on transcriptome sequencing data of hypospadias might provide novel molecular markers and therapeutic targets for hypospadias. First, the microarray data related to hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the differentially expressed lncRNAs and messenger RNAs (mRNAs) related to EMT were screened to construct lncRNA-mRNA co-expression interaction pairs. In addition, the microRNA (miRNA) prediction analysis was performed through bioinformatics methods to construct a ceRNA network. Moreover, function prediction and function enrichment and pathway analyses were also performed. Finally, the core EMT-related lncRNAs were verified based on mRNA expression changes and cell functions. A total of 6 EMT-related lncRNAs were identified and 123 mRNA-lncRNA co-expression interaction pairs were screened in this study. Additionally, a ceRNA regulatory network comprising 17 mRNAs, 4 lncRNAs, and 28 miRNAs was constructed based on the prediction of hypospadias-related miRNAs. The validation results of the dataset GSE121712 revealed that only BEX1 was positively correlated with the expression of the lncRNA GNAS-AS1 (r = 0.874, P < 0.01), both of which had high expression. The cell experiment results demonstrated that interfering with the expression of GNAS-AS1 significantly promoted the proliferation, migration, and EMT of cells. Importantly, it was confirmed that GNAS-AS1 can serve as a ceRNA and play an important role in the EMT of hypospadias. Hence, it may be considered as a potential target in the treatment of this disease.

EMT功能障碍是尿道下裂的主要发病机制。因此,根据尿道下裂的转录组测序数据鉴定与EMT相关的lncRNA可能为尿道下裂提供新的分子标记和治疗靶点。首先,从基因表达总库(Gene Expression Omnibus,GEO)中下载了尿道下裂相关的芯片数据。此外,还筛选了与EMT相关的差异表达的lncRNA和信使RNA(mRNA),以构建lncRNA-mRNA共表达相互作用对。此外,还通过生物信息学方法进行了微RNA(miRNA)预测分析,构建了ceRNA网络。此外,还进行了功能预测、功能富集和通路分析。最后,根据mRNA表达变化和细胞功能验证了与EMT相关的核心lncRNA。本研究共鉴定出6个EMT相关lncRNA,并筛选出123对mRNA-lncRNA共表达相互作用对。此外,在预测尿道下裂相关 miRNA 的基础上,构建了由 17 个 mRNA、4 个 lncRNA 和 28 个 miRNA 组成的 ceRNA 调控网络。数据集GSE121712的验证结果显示,只有BEX1与lncRNA GNAS-AS1的表达呈正相关(r = 0.874,P < 0.01),两者均为高表达。细胞实验结果表明,干扰 GNAS-AS1 的表达会显著促进细胞的增殖、迁移和 EMT。重要的是,实验证实 GNAS-AS1 可作为一种 ceRNA,在尿道下裂的 EMT 中发挥重要作用。因此,它可被视为治疗尿道下裂的潜在靶点。
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引用次数: 0
Revealing the potential role of hub metabolism-related genes and their correlation with immune cells in acute ischemic stroke 揭示枢纽代谢相关基因的潜在作用及其与免疫细胞在急性缺血性中风中的相关性。
IF 1.9 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-06-08 DOI: 10.1049/syb2.12095
Xianjing Zhang, Tengxiao Xu, Chen Wang, Yueyue Lin, Weimi Hu, Maokui Yue, Hao Li

Objectives

Acute ischemic stroke (AIS) is caused by cerebral ischemia due to thrombosis in the blood vessel. The purpose of this study is to identify key genes related to metabolism to aid in the mechanism research and management of AIS.

Materials and Methods

Gene expression data were downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis, Gene Ontology and kyoto encyclopedia of genes and genomes analysis were used to identify metabolism-related genes that may be involved in the regulation of AIS. A protein protein interaction network was mapped using Cytoscape based on the STRING database. Subsequently, hub metabolism-related genes were identified based on Cytoscape-CytoNCA and Cytoscape-MCODE plug-ins. Least absolute shrinkage and selection operator algorithm and differential expression analysis. In addition, drug prediction, molecular docking, ceRNA network construction, and correlation analysis with immune cell infiltration were performed to explore their potential molecular mechanisms of action in AIS. Finally, the expression of hub gene was verified by real-time PCR.

Results

Metabolism-related genes FBL, HEATR1, HSPA8, MTMR4, NDUFC1, NDUFS8 and SNU13 were identified. The AUC values of FBL, HEATR1, HSPA8, MTMR4, NDUFS8 and SNU13 were all greater than 0.8, suggesting that they had good diagnostic accuracy. Correlation analysis found that their expression levels were also related to the infiltration levels of multiple immune cells, such as Activated.CD8.T.cell and Activated.dendritic.cell. It was found that only HSPA8 was successfully matched to drugs with literature support, and these drugs were acetaminophen, bupivacaine, dexamethasone, gentamicin, tretinoin and cisplatin. Moreover, it was also identified that the ENSG000000218510-hsa-miR-330-3p-HEATR1 axis may be involved in regulating AIS.

Conclusions

The identification of FBL, HEATR1, HSPA8, MTMR4, NDUFC1, NDUFS8 and SNU13 provides a new research direction for exploring the molecular mechanisms of AIS, which can help in clinical management and diagnosis.

目的:急性缺血性脑卒中(AIS)是由于血管内血栓形成导致脑缺血引起的。本研究的目的是确定与代谢相关的关键基因,以帮助 AIS 的机制研究和治疗:基因表达数据从基因表达总库数据库下载。加权基因共表达网络分析、基因本体和京都基因和基因组百科全书分析用于识别可能参与调控AIS的代谢相关基因。基于 STRING 数据库,使用 Cytoscape 绘制了蛋白质相互作用网络图。随后,基于Cytoscape-CytoNCA和Cytoscape-MCODE插件确定了枢纽代谢相关基因。采用最小绝对收缩和选择算子算法以及差异表达分析。此外,还进行了药物预测、分子对接、ceRNA 网络构建以及与免疫细胞浸润的相关性分析,以探索其在 AIS 中的潜在分子作用机制。最后,通过实时 PCR 验证了枢纽基因的表达:结果:发现了代谢相关基因FBL、HEATR1、HSPA8、MTMR4、NDUFC1、NDUFS8和SNU13。FBL、HEATR1、HSPA8、MTMR4、NDUFS8和SNU13的AUC值均大于0.8,表明它们具有良好的诊断准确性。相关分析发现,它们的表达水平还与活化的 CD8 T 细胞和活化的树突状细胞等多种免疫细胞的浸润水平有关。研究发现,只有 HSPA8 与有文献支持的药物成功匹配,这些药物是对乙酰氨基酚、布比卡因、地塞米松、庆大霉素、曲替诺和顺铂。此外,还发现ENSG000000218510-hsa-miR-330-3p-HEATR1轴可能参与调控AIS:结论:FBL、HEATR1、HSPA8、MTMR4、NDUFC1、NDUFS8和SNU13的鉴定为探索AIS的分子机制提供了新的研究方向,有助于临床管理和诊断。
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引用次数: 0
Gene signatures of endoplasmic reticulum stress and mitophagy for prognostic risk prediction in lung adenocarcinoma 用于肺腺癌预后风险预测的内质网应激和有丝分裂的基因特征。
IF 2.3 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-05-30 DOI: 10.1049/syb2.12092
Xiong Lin, Miaoling Yang, Yuanling Huang, Xiaoli Huang, Huibo Shi, Binbin Chen, Jianle Kang, Sunkui Ke

Genes associated with endoplasmic reticulum stress (ERS) and mitophagy can be conducive to predicting solid tumour prognosis. The authors aimed to develop a prognosis prediction model for these genes in lung adenocarcinoma (LUAD). Relevant gene expression and clinical information were collected from public databases including Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A total of 265 differentially expressed genes was finally selected (71 up-regulated and 194 downregulated) in the LUAD dataset. Among these, 15 candidate ERS and mitophagy genes (ATG12, CSNK2A1, MAP1LC3A, MAP1LC3B, MFN2, PGAM5, PINK1, RPS27A, SQSTM1, SRC, UBA52, UBB, UBC, ULK1, and VDAC1) might be critical to LUAD based on the expression analysis after crossing with the ERS and mitochondrial autophagy genes. The prediction model demonstrated the ability to effectively predict the 5-, 3-, and 1-year prognoses of LUAD patients in both GEO and TCGA databases. Moreover, high VDAC1 expression was associated with poor overall survival in LUAD (p < 0.001), suggesting it might be a critical gene for LUAD prognosis prediction. Overall, the prognosis model based on ERS and mitophagy genes in LUAD can be useful for evaluating the prognosis of patients with LUAD, and VDAC1 may serve as a promising biomarker for LUAD prognosis.

与内质网应激(ERS)和有丝分裂相关的基因有助于预测实体瘤的预后。作者旨在为肺腺癌(LUAD)中的这些基因开发一个预后预测模型。研究人员从基因表达总库(GEO)和癌症基因组图谱(TCGA)等公共数据库中收集了相关的基因表达和临床信息。最终在 LUAD 数据集中筛选出 265 个差异表达基因(71 个上调,194 个下调)。其中,根据与ERS和线粒体自噬基因交叉后的表达分析,15个候选ERS和线粒体自噬基因(ATG12、CSNK2A1、MAP1LC3A、MAP1LC3B、MFN2、PGAM5、PINK1、RPS27A、SQSTM1、SRC、UBA52、UBB、UBC、ULK1和VDAC1)可能对LUAD至关重要。在GEO和TCGA数据库中,该预测模型都能有效预测LUAD患者的5年、3年和1年预后。此外,VDAC1的高表达与LUAD患者的总生存率低有关(p
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IET Systems Biology
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