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Suffix Graph - An Efficient Approach for Network Motif Mining 后缀图——一种有效的网络Motif挖掘方法
Pub Date : 2016-06-09 DOI: 10.4172/2153-0602.1000200
R. Nikam, U. Chauhan
Network motif is a pattern of inter-connections occurring in complex network in numbers that are significantly higher than those in similar randomized network. The basic premise of finding network motifs lie in the ability to compute the frequency of the subgraphs. In order to discover network motif, one has to compute a subgraph census on the original network that calculates the frequency of all the subgraphs of certain type. Then there is a need to compute the frequency of a set of subgraphs on the randomized similar network. The bottleneck of the entire motif discovery process is therefore to compute the subgraph frequencies and this is the core computational problem. The proposed work is to present the Suffix-Graph, a data structure that store graphs efficiently and to design an algorithm to retrieve subgraph efficiently that detects network motifs and apply them to transcriptional interactions in Escherichia coli.
网络基序是复杂网络中出现的一种相互联系的模式,其数量明显高于类似的随机网络。寻找网络基序的基本前提是计算子图频率的能力。为了发现网络motif,必须在原始网络上计算子图普查,该普查计算所有特定类型的子图的频率。然后需要计算随机相似网络上一组子图的频率。因此,子图频率的计算是整个motif发现过程的瓶颈,也是核心计算问题。提出的工作是提出后缀图,这是一种有效存储图的数据结构,并设计一种算法来检索有效检测网络基序的子图,并将其应用于大肠杆菌的转录相互作用。
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引用次数: 1
Genome Mining of Rice ( Oryza sativa subsp. indica ) for Detection and Characterization of Long Palindromic Sequences 水稻基因组的挖掘。索引)用于长回文序列的检测和表征
Pub Date : 2016-05-30 DOI: 10.4172/2153-0602.1000199
Elmira Katanchi Kheiavi, A. Ahmadikhah, A. M. Mosammam
Because the rice genome has been sequenced entirely, search to find specific features at genome-wide scale is of high importance for studying genome evolution and subsequent applications. Palindromic sequences are important DNA motifs involved in the regulation of different cellular processes and are a potential source of genetic instability. A genome mining approach was applied to detect and characterize the long palindromic sequences in the rice genome. All palindromes, defined as identical inverted repeats with spacer DNA, could be analyzed and sorted according to their frequency, size, GC content, compact index etc. The results showed that the overall palindrome frequency is high in rice genome (nearly 51000 palindromes), that totally cover 41.4% of nuclear genome of rice, with highest and lowest number of palindromes, respectively belongs to chromosome 1 and 12. Palindrome number could well explain the rice chromosome expansion (R2>92%). Average GC content of the palindromic sequences is 42.1%, indicating AT-richness and hence, the low-complexity of palindromic sequences. The results also showed different compact indices of palindromes in different chromosomes (43.2 per cM in chromosome 8 and 34.5 per cM in chromosome 3, as highest and lowest, respectively). Co-location analysis showed that more than 20% of rice genes overlapped with palindromic regions, mainly concentrating on chromosomal arms. Based on the results of this research it can be concluded that the rice genome is rich in long palindromic sequences that triggered most variation during evolution. Generally, both sections of palindromic sequences including stems and loops are AT-rich, indicating that these regions locate in the low-complexity segments of the rice chromosomes.
由于水稻基因组已经完全测序,在全基因组尺度上寻找特定特征对于研究基因组进化及其后续应用具有重要意义。回文序列是参与调控不同细胞过程的重要DNA基序,是遗传不稳定的潜在来源。采用基因组挖掘方法对水稻基因组中的长回文序列进行检测和表征。所有回文,定义为与间隔DNA相同的反向重复序列,可以根据其频率,大小,GC含量,紧凑索引等进行分析和排序。结果表明,水稻基因组总体回文频率较高(近51000个回文),覆盖了41.4%的水稻核基因组,回文频率最高的位于1号染色体,回文频率最低的位于12号染色体。回文数可以很好地解释水稻染色体扩增(R2>92%)。回文序列的平均GC含量为42.1%,表明回文序列具有at丰富度,复杂度较低。不同染色体回文的密实指数也不同(8号染色体最高为43.2 / cM, 3号染色体最低为34.5 / cM)。共定位分析表明,水稻基因中有20%以上与回文区重叠,主要集中在染色体臂上。根据本研究的结果,可以得出结论,水稻基因组富含在进化过程中引发大多数变异的长回文序列。一般来说,包括茎和环在内的回文序列的两个部分都富含at,表明这些区域位于水稻染色体的低复杂性区段。
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引用次数: 3
Visualization of High Throughput Genomic Data Using R and Bioconductor 利用R和Bioconductor实现高通量基因组数据可视化
Pub Date : 2016-05-26 DOI: 10.4172/2153-0602.1000197
R. Yadav, P. Srivastava
DNA microarrays, technology aims at the measurement of mRNA levels in particular cells or tissues for many genes simultaneously. Microarray in molecular biology results in huge datasets that need rigorous computational analysis to extract biological information that lead to some conclusion. From printing of microarray chip to hybridization and scanning process it results in variability in quality of data due to which actual information is either lost or it is over represented. Computational analysis plays an important part related to the processing of the biological information embedded in microarray results and for comparing gene expression result obtained from different samples in different condition for biological interpretation. A basic, yet challenging task is quality control and visualization of microarray gene expression data. One of the most popular platforms for microarray analysis is Bioconductor, an open source and open development software project for the analysis and comprehension of genomic data, based on the R programming language. This paper describes specific procedures for conducting quality assessment of Affymetrix Gene chip using data from GEO database GSE53890 and describes quality control packages of bioconductor with reference to visualization plots for detailed analysis. This paper can be helpful for any researcher working on microarray analysis for quality control analysis of affymetrix chip along with scientific interpretations.
DNA微阵列技术旨在同时测量特定细胞或组织中许多基因的mRNA水平。分子生物学中的微阵列产生了庞大的数据集,需要严格的计算分析来提取生物信息,从而得出一些结论。从微阵列芯片的打印到杂交和扫描过程,它导致数据质量的变化,由于实际信息要么丢失,要么被过度表示。计算分析在处理微阵列结果中嵌入的生物信息以及比较不同条件下不同样品的基因表达结果以进行生物解释方面起着重要作用。微阵列基因表达数据的质量控制和可视化是一项基本但具有挑战性的任务。最流行的微阵列分析平台之一是Bioconductor,这是一个基于R编程语言的开源和开放开发软件项目,用于分析和理解基因组数据。本文介绍了利用GEO数据库GSE53890的数据对Affymetrix基因芯片进行质量评估的具体步骤,并参考可视化图对生物导体的质量控制包进行了详细分析。本文可以为任何从事微阵列分析的研究人员提供科学的解释,用于affymetrix芯片的质量控制分析。
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引用次数: 3
Computational Approach to Identify the Major Histocompatibility Complex Binding Antigenic Peptides from ‘Ascariasis’ 识别蛔虫病主要组织相容性复合体结合抗原肽的计算方法
Pub Date : 2016-05-26 DOI: 10.4172/2153-0602.1000198
S. Mishra, G. Vs
The Ascaris lumbricoides cause ‘ascariasis’ in human and its elimination is the major public concern. In this current investigation, we predicted the MHC (Major Histocompatibility Complex) class I & II binding peptides with computational approach like PSSM (Position Specific Scoring Matrices) and SVM (Support Vector Machine) algorithms. We predict the peptide binders of Cytochrome b (mitochondrion) protein from Ascaris lumbricoide sequence to MHC-I molecules are as 11mer_H2_Db, 10mer_H2_Db, 9mer_H2_Db, 8mer_H2_Db. Also study integrates prediction of peptide MHC class I binding; proteasomal C terminal cleavage and TAP transport efficiency by using sequence and properties of the amino acids. We also found the binding of peptides to different alleles by using Position Specific Scoring Matrix. Cytochrome B from Ascaris lumbricoides (365 residues long) with 357 nonamers having antigenic MHC binding peptides. PSSM based server will predict the peptide binders from sequence to MHCII molecules are as I_Ab.p, I_Ad.p, I_Ag7, which are found antigenic epitopes region in Cytochrome B from Ascaris lumbricoides. This investigation can be useful in rational vaccine design and simultaneously increase the understanding the role of the immune system against antigenic.
类蛔虫引起人类“蛔虫病”,其消除是公众关注的主要问题。在目前的研究中,我们用PSSM(位置特定评分矩阵)和SVM(支持向量机)算法等计算方法预测了MHC(主要组织相容性复合体)I类和II类结合肽。我们预测蛔虫线粒体色素b蛋白与mhc - 1分子的肽结合物分别为11mer_H2_Db、10mer_H2_Db、9mer_H2_Db、8mer_H2_Db。同时研究了MHC I类肽结合的综合预测;利用氨基酸的序列和性质研究蛋白酶体C端裂解和TAP的转运效率。我们还利用位置特异性评分矩阵发现了多肽与不同等位基因的结合。细胞色素B来自蛔虫(365个残基长),有357个具有抗原MHC结合肽的名字。基于PSSM的服务器将预测从序列到MHCII分子的肽结合物为I_Ab。p, I_Ad。p, I_Ag7,这是蛔虫细胞色素B的抗原表位区域。这项研究有助于合理设计疫苗,同时增加对免疫系统抗抗原作用的认识。
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引用次数: 1
Infectomic Insights into the Roles of Exosymbiosis-Endosymbiosis Imbalance (EESI) in HIV-1 and SIV Infections 外共生-内共生失衡(EESI)在HIV-1和SIV感染中的作用
Pub Date : 2016-04-30 DOI: 10.4172/2153-0602.1000196
Sheng-He Huang, Yanhong Zhou
The vast majority of microbes form a healthy symbiotic ‘superorganism’ with the hosts. There are two types of symbiosis (Sym), exosymbiosis (e.g. microbiota) and endosymbiosis (e.g. mitochondria). It has been suggested that the exo-endo Sym balance (EESB) highly contribute to maintain the host homeostasis. However, alterations to the EESB caused by microbial (e.g. bacterial and viral pathogens) and non-microbial factors (e.g. substance abuse, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and acquired immune deficiency syndrome (AIDS). Progressive AIDS caused by human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) is characterized by systemic inflammation, opportunistic infection and malignant disorders resulting from generalized immune activation-mediated destruction of the healthy symbiotic super organism. Two extreme phenotypes are present in both HIV and SIV infections, including slow or rapid progression to AIDS (Pat: pathogenesis) in a majority of the infected human subjects and the non-natural primate host (i.e. rhesus macaques, RMs), and nonprogression to AIDS (Sym) in a minority of the infected people and the natural primate hosts (i.e. sooty mangabeys, SMs). Recently, it has been demonstrated that both exosymbiotic and endosymbiotic disorders contribute to the development of AIDS through infectomic studies of the extreme phenotypes of HIV/SIV infections. The involvement of the EESB in the pathogenesis and therapeutics of HIV infections is becoming increasingly clear. Indeed, many changes in the microbial diversity, abundance and composition of the gut microbiota and mitochondrial functions have been reported in HIV/AIDS, suggesting that there exist EESB problems in this disease. HIV virotoxins have been implicated in exploiting mitochondria to promote the targeted progressive and inexorable depletion of key immune cells (e.g. CD4 T cells), a hallmark of HIV/SIV infections. These findings support the notion that the exo-endo Sym imbalance (EESI) may play a central role in epidemiology, pathogenesis and management of infectious diseases, including AIDS caused by HIV-1 and SIV. Correction of the EESI problems in HIV/SIV infections may lead to a rational control of AIDS.
绝大多数微生物与宿主形成一种健康的共生“超级有机体”。有两种类型的共生(Sym),外共生(如微生物群)和内共生(如线粒体)。研究表明,体外系统平衡(EESB)在维持宿主体内平衡中起着重要作用。然而,由微生物(如细菌和病毒病原体)和非微生物因素(如药物滥用、饮食和/或生活方式)引起的EESB改变可扰乱这种共生关系,并促进疾病,如炎症性肠病和获得性免疫缺陷综合征(艾滋病)。由人类免疫缺陷病毒(HIV)和猿猴免疫缺陷病毒(SIV)引起的进行性艾滋病的特点是全身炎症、机会性感染和恶性疾病,这些疾病是由免疫激活介导的健康共生超级有机体的破坏引起的。在HIV和SIV感染中都存在两种极端的表型,包括在大多数受感染的人类受试者和非天然灵长类宿主(即恒河猴,RMs)中缓慢或快速进展为艾滋病(发病机制),以及在少数受感染的人和自然灵长类宿主(即黑白头猴,SMs)中不进展为艾滋病(Sym)。最近,通过对HIV/SIV感染的极端表型的感染学研究,已经证明了外共生和内共生疾病都有助于艾滋病的发展。EESB在HIV感染的发病机制和治疗中的作用越来越清楚。事实上,据报道,在HIV/AIDS中,微生物多样性、肠道微生物群的丰度和组成以及线粒体功能发生了许多变化,这表明该疾病存在EESB问题。HIV病毒毒素与利用线粒体促进关键免疫细胞(如CD4 T细胞)的靶向进行性和不可阻挡的耗竭有关,这是HIV/SIV感染的标志。这些发现支持了外端sydo失衡(EESI)可能在包括HIV-1和SIV引起的艾滋病在内的传染病的流行病学、发病机制和管理中发挥核心作用的观点。纠正HIV/SIV感染中的EESI问题,可以实现对艾滋病的合理控制。
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引用次数: 0
Impaired Immune Phenotype of Endothelial Cell-derived Micro Particles: The Missing Link between Diabetes-related States and Risk of Cardiovascular Complications? 内皮细胞衍生的微颗粒免疫表型受损:糖尿病相关状态与心血管并发症风险之间的缺失环节?
Pub Date : 2016-04-28 DOI: 10.4172/2153-0602.1000195
Alex, er E. Berezin
Type two diabetes mellitus (T2DM) remains a leading contributor to cardiovascular (CV) mortality worldwide. Although obese and metabolic syndrome are discussed key factors contributing a higher risk of T2DM, the exact molecular mechanisms underlying to the progression of dysmetabolic states are still not completely clear. There is large body of evidence regarding endothelial dysfunction as a key player in increasing CV risk and that vascular damage in the dysmetabolic patients might mediate through an imbalance between various populations of micro particle (MP). The short commentary is discussed a role of impaired ratio between apoptotic MPs and activated MPs derived from endothelial cells that was recognized as “impaired phenotype” of endothelial cell-derived MPs. It has considered the causality epigenetic reprogramming, metabolic disorders, inflammation, and oxidative stress in forming of “impaired phenotype” of MPs. The incorporation of measurement of the endothelial cell-derived MP number into a conventional CV risk factor model aimed improving of risk stratification of the dysmetabolic patients with high probability of CV disease is discussed.
2型糖尿病(T2DM)仍然是全球心血管(CV)死亡的主要原因。虽然肥胖和代谢综合征被认为是导致T2DM高风险的关键因素,但代谢异常状态进展的确切分子机制仍不完全清楚。有大量证据表明,内皮功能障碍是增加心血管风险的关键因素,代谢异常患者的血管损伤可能通过不同微颗粒(MP)群体之间的不平衡来调节。这篇简短的评论讨论了内皮细胞中凋亡MPs和活化MPs之间的比例受损的作用,这被认为是内皮细胞来源MPs的“受损表型”。它考虑了表观遗传重编程、代谢紊乱、炎症和氧化应激在MPs“受损表型”形成中的因果关系。本文讨论了将内皮细胞来源的MP数测量纳入传统的心血管危险因素模型,旨在改善高概率心血管疾病代谢异常患者的风险分层。
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引用次数: 35
The Importance of Next-generation Sequencing for Marine Larvae Research: Insight into Larvae Settlement and Anti-fouling 新一代测序对海洋幼虫研究的重要性:对幼虫沉降和抗污染的洞察
Pub Date : 2016-04-16 DOI: 10.4172/2153-0602.1000E123
Kondethimmanahalli Ch, ramouli
Larvae of marine invertebrates are important constituents of intertidal and sediment marine ecosystems around the world. They are ecologically and economically important species. For example, the barnacles are most dominant group of fouling organisms and are extensively used in larval settlement and anti-fouling research [1]. The bryozons and polychaetes are also cosmopolitan fouling organisms distributed in intertidal to shallow subtidal water [2,3]. These species form large colonies on ship hulls, piers and underwater structures causing a serious economic loss to shipping industries. It has been reported that biofouling of such species cost billions of dollars in shipping industry [4]. The academic and industrial marine research is mainly focused on biofouling species with the goal of understanding their larval settlement process and hoping for prevention of settlement and accumulation of such species on underwater structures. The life cycle of most marine invertebrates has two distinct stages: the pelagic larvae and the adults attached to marine substratum [5]. Understanding the larval settlement and attachment processes is important for prevention of biofouling. Most of the anti-fouling studies target larvae settlement process. However, process of settlement at molecular level is largely unknown due to limited genome information available for these species. In recent years, rapid technological advances in next-generation sequencers (NGS) have opened up possibilities to sequence larval transcriptome of marine invertebrates. Since NGS rapidly generates huge amount of sequence data in a very cost-effective way, larval biologists are now starting to integrate such sequencing methods into their research methods.
海洋无脊椎动物幼虫是全球潮间带和沉积物海洋生态系统的重要组成部分。它们是生态和经济上重要的物种。例如,藤壶是最主要的污垢生物,被广泛用于幼虫沉降和抗污垢研究[1]。苔藓虫和多毛体也是分布在潮间带至浅海潮下的世界性污染生物[2,3]。这些物种在船体、码头和水下结构物上形成大量的殖民地,给航运业造成严重的经济损失。据报道,这类物种的生物污染给航运业造成了数十亿美元的损失[4]。学术界和工业界的海洋研究主要集中在生物污染物种上,目的是了解其幼虫的沉降过程,并希望防止这些物种在水下结构物上的沉降和积累。大多数海洋无脊椎动物的生命周期有两个不同的阶段:上层幼虫和附着在海洋基质上的成虫[5]。了解幼虫的沉降和附着过程对预防生物污染很重要。大多数的防污研究都是针对幼虫的沉降过程。然而,由于基因组信息有限,这些物种在分子水平上的定居过程在很大程度上是未知的。近年来,下一代测序仪(NGS)技术的快速发展为海洋无脊椎动物幼虫转录组测序提供了可能。由于NGS以非常经济的方式快速生成大量序列数据,幼虫生物学家现在开始将这种测序方法整合到他们的研究方法中。
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引用次数: 1
Identification of Novel Cdc37 Interacting Proteins and Pathways in Human Alzheimers Disease Brain Tissue Using Mass Spectrometry 用质谱法鉴定人类阿尔茨海默病脑组织中新的Cdc37相互作用蛋白和途径
Pub Date : 2016-03-07 DOI: 10.4172/2153-0602.1000193
M. Narayan, Lisa Kirouac, Dale Chaput, S. Stevens, J. Padmanabhan, U. Jinwal
Alzheimer’s disease (AD) is the most common form of dementia and the 6th leading cause of death in the United States. The major pathological hallmarks observed in AD include the formation of intracellular neurofibrillary tangles comprised of phosphorylated forms of the microtubule associated protein tau, and the deposition of extracellular plaques composed of amyloid beta. Cdc37 is a co-chaperone of Hsp90, which recruits client kinases to the Hsp90 complex for folding and stabilization. It has been previously shown that Cdc37 can not only bind and preserve tau, but also stabilize kinases that can phosphorylate tau. The goal of the current study was to identify novel Cdc37- interacting proteins in human AD tissue compared to normal tissue using an immunoprecipitation-based approach combined with mass spectrometry. We identified 39 unique proteins that interacted with Cdc37 in AD samples only and 7 proteins that interacted with Cdc37 in normal samples only. 39 proteins were found to bind Cdc37 in both AD and normal tissue. Of these, 18 showed increased interaction in AD tissue, 10 showed increased interaction in normal tissue and 11 showed equal nteraction in both samples. Ingenuity Pathway Analysis of the data indicates that these Cdc37-interacting proteins could signal through the p70S6K, PI3K / Akt, TGFs, ErbB, NF- kB, calmodulin, p38 MAPK and JNK pathways. Identification of these novel proteins and pathways linked to Cdc37 may indicate its role both as a non-kinase co-chaperone and in other pathways in the AD brain.
阿尔茨海默病(AD)是最常见的痴呆症,也是美国第六大死亡原因。在AD中观察到的主要病理标志包括由微管相关蛋白tau磷酸化形式组成的细胞内神经原纤维缠结的形成,以及由淀粉样蛋白组成的细胞外斑块的沉积。Cdc37是Hsp90的共同伴侣,它将客户激酶招募到Hsp90复合体中进行折叠和稳定。先前的研究表明,Cdc37不仅可以结合和保存tau蛋白,还可以稳定磷酸化tau蛋白的激酶。当前研究的目的是使用基于免疫沉淀的方法结合质谱法,与正常组织相比,鉴定人类AD组织中新的Cdc37相互作用蛋白。我们鉴定出39种独特的蛋白仅在AD样品中与Cdc37相互作用,7种蛋白仅在正常样品中与Cdc37相互作用。在AD和正常组织中均发现39种蛋白与Cdc37结合。其中,18个在AD组织中表现出增加的相互作用,10个在正常组织中表现出增加的相互作用,11个在两个样本中表现出相同的相互作用。数据分析表明,这些与cdc37相互作用的蛋白可以通过p70S6K、PI3K / Akt、tgf、ErbB、NF- kB、calmodulin、p38 MAPK和JNK通路发出信号。这些与Cdc37相关的新蛋白和途径的鉴定可能表明其在AD脑中的非激酶共伴侣和其他途径中的作用。
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引用次数: 7
Marine Proteomics: Challenges and Opportunities 海洋蛋白质组学:挑战与机遇
Pub Date : 2016-03-02 DOI: 10.4172/2153-0602.1000E122
Kondethimmanahalli Ch, ramouli
Marine invertebrates such as crustaceans, oysters, polychaetes and bryozones are widely distributed in intertidal and sediment ecosystems and have significant economic and ecological importance. These species serve as model organisms for settlement biology, biofouling, marine pollution, toxicology, climate change and ocean acidification research. Traditionally, marine biologists have studied them in the context of morphology and behavior. Ever since the technological advancement in proteomics and genome sequencing tools, researchers began to adopt such tools in marine larvae biology research [1]. However, the challenge is that none of these tools were applied to marine research before so there is a great deal of optimization of such methods has to be done. In addition, lack of genome information discouraged marine scientists to conduct proteomics studies. Cell culture methods have not been established and species specific antibodies are not yet developed. The direct use of larvae or adults increases the complexity of proteome. Shells and calcareous tubes of crustaceans and oysters and self-secreted mucilage or slime of polychaetes poses greater challenge for proteins extraction and purification protocols. Natural habitat conditions differ substantially thereby variation in data obtained is high.
海洋无脊椎动物如甲壳类、牡蛎类、多毛类和苔藓带广泛分布于潮间带和沉积物生态系统中,具有重要的经济和生态意义。这些物种是沉降生物学、生物污染、海洋污染、毒理学、气候变化和海洋酸化研究的模式生物。传统上,海洋生物学家在形态和行为的背景下研究它们。随着蛋白质组学和基因组测序工具的技术进步,研究人员开始在海洋幼虫生物学研究中使用这些工具[1]。然而,挑战在于这些工具之前都没有应用于海洋研究,因此必须对这些方法进行大量优化。此外,基因组信息的缺乏阻碍了海洋科学家进行蛋白质组学研究。细胞培养方法尚未建立,物种特异性抗体尚未开发。直接使用幼虫或成虫增加了蛋白质组的复杂性。甲壳类动物和牡蛎的壳和钙质管以及多毛类动物的自分泌粘液或黏液对蛋白质的提取和纯化方案提出了更大的挑战。自然生境条件差别很大,因此所获得的数据差异很大。
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引用次数: 3
Genome-wide Analysis of Acute Inflammatory and Anti-Inflammatory Responses in RAW264 Cells Suggests cis-Elements Associated with Translational Regulation RAW264细胞急性炎症和抗炎反应的全基因组分析表明顺式元件与翻译调控相关
Pub Date : 2016-02-28 DOI: 10.4172/2153-0602.1000191
H. Sako, Katsuhiko Suzuki
Translational regulation plays pivotal roles in mediating inflammatory responses. Glucocorticoids, represented in this study by dexamethasone (DEX), are widely recognized anti-inflammatory agents that exert significant inhibitory effects on the translation of diverse gene groups, including inflammatory genes. However, their regulation is highly complex and diverse, involving transcriptional and translational regulation. Although transcriptional regulation has been investigated by genome-wide transcriptome analyses, translational regulation has been studied by only a few specific gene targets (e.g., Tumor necrosis factor) and the global impact of glucocorticoids on translation levels has scarcely been studied, mainly due to its technical difficulty. Here, using ribosome profiling coupled with high-throughput mRNA sequencing (mRNA-Seq) in which footprints of translating ribosomes can be captured, we conducted a genomewide transcriptional and translational analysis of the acute inflammatory or anti-inflammatory responses of RAW264 cells stimulated by lipopolysaccharide (LPS) or LPS coupled with DEX (LPS + DEX). We showed that the majority of the differential regulation between LPS alone and LPS + DEX were predominated by translation levels rather than transcription levels. Further analysis on the up- and down-regulated gene clusters revealed putative cis regulatory elements exclusively enriched in the 3'-UTR of either up- or down-regulated genes induced by LPS + DEX. The results imply an alternative to the currently recognized mechanisms of glucocorticoid-induced translational regulation in the acute inflammatory response of RAW264 cells.
翻译调节在介导炎症反应中起着关键作用。以地塞米松(dexamethasone, DEX)为代表的糖皮质激素是公认的抗炎药物,对多种基因群(包括炎症基因)的翻译具有显著的抑制作用。然而,它们的调控是高度复杂和多样的,涉及转录和翻译调控。虽然转录调控已经通过全基因组转录组分析进行了研究,但翻译调控仅通过少数特定的基因靶点(如肿瘤坏死因子)进行了研究,糖皮质激素对翻译水平的整体影响几乎没有研究,这主要是由于其技术难度。在这里,我们使用核糖体分析结合高通量mRNA测序(mRNA- seq),其中可以捕获翻译核糖体的足迹,我们对脂多糖(LPS)或脂多糖与DEX (LPS + DEX)偶联的RAW264细胞的急性炎症或抗炎反应进行了全基因组转录和翻译分析。我们发现LPS单独和LPS + DEX之间的差异调控主要是翻译水平而不是转录水平。对上调和下调基因簇的进一步分析显示,LPS + DEX诱导的上调或下调基因的3'- utr中只富集了推测的顺式调控元件。这些结果暗示了在RAW264细胞急性炎症反应中糖皮质激素诱导的翻译调节机制的另一种选择。
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引用次数: 1
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