Protein–protein interaction(PPI)network analysis is an effective method to identify key proteins during plant development,especially in species for which basic molecular research is lacking,such as apple(Malus domest...Protein–protein interaction(PPI)network analysis is an effective method to identify key proteins during plant development,especially in species for which basic molecular research is lacking,such as apple(Malus domestica).Here,an MdPPI network containing 30806 PPIs was inferred in apple and its quality and reliability were rigorously verified.Subsequently,a rootgrowth subnetwork was extracted to screen for critical proteins in root growth.Because hormone-related proteins occupied the largest proportion of critical proteins,a hormonerelated sub-subnetwork was further extracted from the root-growth subnetwork.Among these proteins,auxin-related M.domestica TRANSPORT INHIBITOR RESISTANT 1(MdTIR1)served as the central,high-degree node,implying that this protein exerts essential roles in root growth.Furthermore,transgenic apple roots overexpressing an MdTIR1 transgene displayed increased primary root elongation.Expression analysis showed that MdTIR1 significantly upregulated auxin-responsive genes in apple roots,indicating that it mediates root growth in an auxin-dependent manner.Further experimental validation revealed that MdTIR1 interacted with and accelerated the degradation of MdIAA28,MdIAA43,andMdIAA46.Thus,MdTIR1-mediated degradation of MdIAAs is critical in auxin signal transduction and root growth regulation in apple.Moreover,our network analysis and high-degree node screening provide a novel research technique for more generally characterizing molecular mechanisms.展开更多
Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehe...Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management.In this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of LUSC.Gene expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database.Differentially expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of data.CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in LUSC.Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment.Together,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.展开更多
由于PPI网络数据的无尺度和小世界特性,使得目前对此类数据的聚类算法效果不理想.根据PPI网络的拓扑结构特性,本文提出了一种基于连接强度的蚁群优化(Joint Strength based Ant Colony Optimization,JSACO)聚类算法,该算法引入了连接强...由于PPI网络数据的无尺度和小世界特性,使得目前对此类数据的聚类算法效果不理想.根据PPI网络的拓扑结构特性,本文提出了一种基于连接强度的蚁群优化(Joint Strength based Ant Colony Optimization,JSACO)聚类算法,该算法引入了连接强度的概念对蚁群聚类算法中的拾起/放下规则加以改进,以连接强度作为拾起规则,对结点进行聚类,并根据放下规则放弃部分不良数据,产生最终聚类结果.最后采用了MIPS数据库中的PPI数据进行实验,将JSACO算法与PPI网络数据的其他聚类算法进行比较,聚类结果表明JSACO算法正确率高,时间开销低.展开更多
针对蚁群聚类在蛋白质相互作用(protein-protein interaction,PPI)网络中进行功能模块检测问题上时间性能的不足,提出一种快速的基于蚁群聚类的PPI网络功能模块检测(fast ant colony clustering for functional module detection,FACC-F...针对蚁群聚类在蛋白质相互作用(protein-protein interaction,PPI)网络中进行功能模块检测问题上时间性能的不足,提出一种快速的基于蚁群聚类的PPI网络功能模块检测(fast ant colony clustering for functional module detection,FACC-FMD)方法.该算法计算每个蛋白质与核心组蛋白质的相似度,根据拾起放下模型进行聚类,得到的初始聚类结果中功能模块之间相似度很小,省去了原始蚁群聚类算法中的合并和过滤操作,缩短了求解时间.同时该算法根据蛋白质的关键性对蚁群聚类中的拾起放下操作做了更严格的约束,以减少拾起放下的次数,加速了聚类的过程.在多个PPI网络上的实验表明:与原始蚁群聚类方法相比,FACC-FMD大幅度提高了时间性能,同时取得了良好的检测质量,而且与近年来的一些经典算法相比在多项性能指标上也具有一定的优势.展开更多
Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported t...Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.展开更多
Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have b...Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have been proposed to identify essential proteins. Unfortunately, most methods based on network topology only consider the interactions between a protein and its neighboring proteins, and not the interactions with its higher-order distance proteins. In this paper, we propose the DSEP algorithm in which we integrated network topology properties and subcellular localization information in protein–protein interaction(PPI) networks based on four-order distances, and then used random walks to identify the essential proteins. We also propose a method to calculate the finite-order distance of the network, which can greatly reduce the time complexity of our algorithm. We conducted a comprehensive comparison of the DSEP algorithm with 11 existing classical algorithms to identify essential proteins with multiple evaluation methods. The results show that DSEP is superior to these 11 methods.展开更多
目的研究毗邻锌指结构域的溴结构域蛋白2A(bromodomain adjacent to zinc finger domain protein 2,BAZ2A)促进子宫颈癌和肝癌发展的共同机制。方法通过转录组测序获得子宫颈癌组和肝癌组的转录组数据。应用R语言的“limma”包分别筛选...目的研究毗邻锌指结构域的溴结构域蛋白2A(bromodomain adjacent to zinc finger domain protein 2,BAZ2A)促进子宫颈癌和肝癌发展的共同机制。方法通过转录组测序获得子宫颈癌组和肝癌组的转录组数据。应用R语言的“limma”包分别筛选子宫颈癌组DEGs和肝癌组DEGs,并取交集获得其共有DEGs。通过“ggplot2”和“clusterProfiler”包对DEGs进行GO和KEGG功能注释分析。应用STRING数据库在线工具构建子宫颈癌DEGs、肝癌DEGs和共有DEGs的PPI网络分析图。使用Cytoscape软件对PPI网络分析图进行进一步处理,鉴定出核心基因。结果对子宫颈癌DEGs、肝癌DEGs和共有DEGs分别进行KEGG富集,三者共有的通路涉及细胞凋亡、抗原加工与呈递、类固醇生物合成。对子宫颈癌DEGs、肝癌DEGs和共有DEGs分别进行GO富集,前两者共有的生物过程(biological process,BP)条目涉及凋亡信号通路、免疫反应、生物黏附,三者共有的BP条目为细胞-底物黏附。子宫颈癌DEGs的核心基因为EP300。EP300对癌症细胞凋亡、迁移有调控作用。肝癌DEGs的核心基因为HSP90AB1。HSP90AB1可介导细胞程序性死亡、炎症和自身免疫、迁移等过程。共有DEGs的核心基因为RPS3。RPS3是一种核糖体蛋白,可通过影响核糖体的生物发生而影响癌细胞的生长、增殖和转移。结论BAZ2A可通过调节细胞凋亡、免疫反应、细胞运动、迁移而影响子宫颈癌、肝癌的发展,这为癌症的靶向治疗提供了新思路。展开更多
基金supported by the National Natural Science Foundation of China(31972357,31901574,and 31772254)the National Key R&D Program of China(2019YFD1000104)。
文摘Protein–protein interaction(PPI)network analysis is an effective method to identify key proteins during plant development,especially in species for which basic molecular research is lacking,such as apple(Malus domestica).Here,an MdPPI network containing 30806 PPIs was inferred in apple and its quality and reliability were rigorously verified.Subsequently,a rootgrowth subnetwork was extracted to screen for critical proteins in root growth.Because hormone-related proteins occupied the largest proportion of critical proteins,a hormonerelated sub-subnetwork was further extracted from the root-growth subnetwork.Among these proteins,auxin-related M.domestica TRANSPORT INHIBITOR RESISTANT 1(MdTIR1)served as the central,high-degree node,implying that this protein exerts essential roles in root growth.Furthermore,transgenic apple roots overexpressing an MdTIR1 transgene displayed increased primary root elongation.Expression analysis showed that MdTIR1 significantly upregulated auxin-responsive genes in apple roots,indicating that it mediates root growth in an auxin-dependent manner.Further experimental validation revealed that MdTIR1 interacted with and accelerated the degradation of MdIAA28,MdIAA43,andMdIAA46.Thus,MdTIR1-mediated degradation of MdIAAs is critical in auxin signal transduction and root growth regulation in apple.Moreover,our network analysis and high-degree node screening provide a novel research technique for more generally characterizing molecular mechanisms.
基金Department of Science and Technology of Yunnan Province,Provincial Basic Research Program(Kunkun-Medical Joint Special Project),202101AY070001-134Yunnan Provincial Department of Science and Technology,Yunnan Provincial Gerontology Research Center,202102AA310069Yunnan Provincial Department of Science and Technology-Kunming Medical University Basic Research Joint Special Key Project,202201AY070001-136.
文摘Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management.In this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of LUSC.Gene expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database.Differentially expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of data.CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in LUSC.Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment.Together,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.
文摘由于PPI网络数据的无尺度和小世界特性,使得目前对此类数据的聚类算法效果不理想.根据PPI网络的拓扑结构特性,本文提出了一种基于连接强度的蚁群优化(Joint Strength based Ant Colony Optimization,JSACO)聚类算法,该算法引入了连接强度的概念对蚁群聚类算法中的拾起/放下规则加以改进,以连接强度作为拾起规则,对结点进行聚类,并根据放下规则放弃部分不良数据,产生最终聚类结果.最后采用了MIPS数据库中的PPI数据进行实验,将JSACO算法与PPI网络数据的其他聚类算法进行比较,聚类结果表明JSACO算法正确率高,时间开销低.
文摘针对蚁群聚类在蛋白质相互作用(protein-protein interaction,PPI)网络中进行功能模块检测问题上时间性能的不足,提出一种快速的基于蚁群聚类的PPI网络功能模块检测(fast ant colony clustering for functional module detection,FACC-FMD)方法.该算法计算每个蛋白质与核心组蛋白质的相似度,根据拾起放下模型进行聚类,得到的初始聚类结果中功能模块之间相似度很小,省去了原始蚁群聚类算法中的合并和过滤操作,缩短了求解时间.同时该算法根据蛋白质的关键性对蚁群聚类中的拾起放下操作做了更严格的约束,以减少拾起放下的次数,加速了聚类的过程.在多个PPI网络上的实验表明:与原始蚁群聚类方法相比,FACC-FMD大幅度提高了时间性能,同时取得了良好的检测质量,而且与近年来的一些经典算法相比在多项性能指标上也具有一定的优势.
基金supported by the National Natural Science Foundation of China,No.81870975(to SZ)。
文摘Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.
基金Project supported by the Gansu Province Industrial Support Plan (Grant No.2023CYZC-25)the Natural Science Foundation of Gansu Province (Grant No.23JRRA770)the National Natural Science Foundation of China (Grant No.62162040)。
文摘Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have been proposed to identify essential proteins. Unfortunately, most methods based on network topology only consider the interactions between a protein and its neighboring proteins, and not the interactions with its higher-order distance proteins. In this paper, we propose the DSEP algorithm in which we integrated network topology properties and subcellular localization information in protein–protein interaction(PPI) networks based on four-order distances, and then used random walks to identify the essential proteins. We also propose a method to calculate the finite-order distance of the network, which can greatly reduce the time complexity of our algorithm. We conducted a comprehensive comparison of the DSEP algorithm with 11 existing classical algorithms to identify essential proteins with multiple evaluation methods. The results show that DSEP is superior to these 11 methods.
文摘目的研究毗邻锌指结构域的溴结构域蛋白2A(bromodomain adjacent to zinc finger domain protein 2,BAZ2A)促进子宫颈癌和肝癌发展的共同机制。方法通过转录组测序获得子宫颈癌组和肝癌组的转录组数据。应用R语言的“limma”包分别筛选子宫颈癌组DEGs和肝癌组DEGs,并取交集获得其共有DEGs。通过“ggplot2”和“clusterProfiler”包对DEGs进行GO和KEGG功能注释分析。应用STRING数据库在线工具构建子宫颈癌DEGs、肝癌DEGs和共有DEGs的PPI网络分析图。使用Cytoscape软件对PPI网络分析图进行进一步处理,鉴定出核心基因。结果对子宫颈癌DEGs、肝癌DEGs和共有DEGs分别进行KEGG富集,三者共有的通路涉及细胞凋亡、抗原加工与呈递、类固醇生物合成。对子宫颈癌DEGs、肝癌DEGs和共有DEGs分别进行GO富集,前两者共有的生物过程(biological process,BP)条目涉及凋亡信号通路、免疫反应、生物黏附,三者共有的BP条目为细胞-底物黏附。子宫颈癌DEGs的核心基因为EP300。EP300对癌症细胞凋亡、迁移有调控作用。肝癌DEGs的核心基因为HSP90AB1。HSP90AB1可介导细胞程序性死亡、炎症和自身免疫、迁移等过程。共有DEGs的核心基因为RPS3。RPS3是一种核糖体蛋白,可通过影响核糖体的生物发生而影响癌细胞的生长、增殖和转移。结论BAZ2A可通过调节细胞凋亡、免疫反应、细胞运动、迁移而影响子宫颈癌、肝癌的发展,这为癌症的靶向治疗提供了新思路。