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1.
    
Cancer of the gingivo-buccal complex (GBC) is a major cancer in Indian men. This study reports the identification of tumor antigens, which elicit an antibody response in cancer of GBC using immunoproteomics. Proteins from KB cells separated by 2-D PAGE, were immunoblotted with IgG from sera of 28 cancer patients, 12 patients with leukoplakia, and 28 healthy individuals. Antigens detected by the IgGs from the patient's sera were different among different individuals with presence of any single antigen ranging from 7 to 79%. Several of these antigens have been identified by MS and confirmed by immunostaining. They are three forms of α-enolase, peroxiredoxin-VI, annexin-II, HSP70, pyruvate kinase, α-tubulin, β-tubulin, ATP-synthase, phosphoglycerate mutase (PGM), aldose reductase, triosephosphate isomerase, and cyclophilin-A. Except, HSP70, these antigens are being reported in cancer of GBC for the first time. Pyruvate kinase and aldose reductase have not been reported to elicit autoantibody response in any other cancer earlier. Initial results show that autoantibody response against α-enolase, HSP70, annexin-II, peroxiredoxin-VI, and aldose reductase are also seen in patients with leukoplakia of GBC, which suggest early occurrence of these autoantibodies during the process of oral carcinogenesis. These antigens can be further validated for their use in cancer management by immune intervention.  相似文献   

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Autoimmune diseases, such as antiphospholipid syndrome, systemic lupus erythematosus, and rheumatoid arthritis, are characterized by a high prevalence of cardiovascular (CV) disease (CVD), which constitutes the leading causes of morbidity and mortality among such patients. Although such effects are partly explained by a higher prevalence of traditional CV risk factors, many studies indicate that such factors do not fully explain the enhanced CV risk in these patients. In addition, risk stratification algorithms based upon traditional CV risk factors are not as predictive in autoimmune diseases as in the general population. For these reasons, the timely and accurate assessment of CV risk in these high-risk populations still remains an unmet clinical need. An enhanced contribution of different inflammatory components of the immune response, as well as autoimmune elements (e.g. autoantibodies, autoantigens, and cellular response), has been proposed to underlie the incremental CV risk observed in these populations. Recent advances in proteomic tools have contributed to the discovery of proteins involved in CVDs, including some that may be suitable to be used as biological markers. In this review we summarize the main markers in the field of CVDs associated with autoimmunity, as well as the recent advances in proteomic technology and their application for biomarker discovery in autoimmune disease.  相似文献   

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Standard classification of glomerular diseases is based on histopathologic abnormalities. The recent application of proteomic technologies has resulted in paradigm changes in the understanding and classification of idiopathic membranous nephropathy and membranoproliferative glomerulonephritis. Those examples provide evidence that proteomics will lead to advances in understanding of the molecular basis of other glomerular diseases, such as lupus nephritis. Proof of principle experiments show that proteomics can be applied to patient renal biopsy specimens. This viewpoint summarizes the advances in immune-mediated glomerular diseases that have relied on proteomics, and potential future applications are discussed.  相似文献   

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Each of the currently available methods for serodiagnosis of leptospirosis, including the microscopic agglutination test (MAT), has its own drawback(s) when used in clinical practice. A new diagnostic test is therefore required for an earlier and more accurate diagnosis of leptospirosis. We applied immunoproteomics to define potential immunogens from five serovars of Leptospira reference strains. A leptospiral whole cell lysate from each serovar was used as the antigen to react with IgG and IgM in the sera from four patients with a positive MAT. Sera from four non-leptospirosis patients with a negative MAT were pooled and used as the negative control. 2-D Western blot analysis showed that the degree of immunoreactivity corresponded with the MAT titers. No immunoreactive spots were detected when the pooled control sera were used. A total of 24 protein spots immunoreacted with IgM and/or IgG from patients with leptospirosis. These immunoreactive proteins were identified by MALDI-TOF MS and were classified into five groups, including flagellar proteins, chaperones/heat shock proteins, transport proteins, metabolic enzymes, and hypothetical proteins. More immunoreactive spots were detected with anti-human IgG in the sera of all patients and with all the serovars of leptospires used. Some of the identified proteins immunoreacted only with IgG, whereas the others were detectable with both IgM and IgG. Among the immunoreactive proteins identified, FlaB proteins (flagellin and flagellar core protein) have been shown to have a potential role in clinical diagnostics and vaccine development. These data underscore the significant impact of immunoproteomics in clinical applications.  相似文献   

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Coxiella burnetii, the causative agent of Q fever, is an intracellular bacterium and a potential weapon for bioterrorism. The widespread throughout the world, zoonosis is manifested clinically as a self-limited febrile illness, as pneumonia (acute Q fever) or as a chronic illness with endocarditis being its major complication. The recent Netherlands Q fever outbreak has driven the bacterium from a relatively cryptic, underappreciated, “niche” microorganism on the sideline of bacteriology, to one of possibly great impact on public health. Advances in the study of this microorganism proceeded slowly, primarily due to the, until recently, obligatory intracellular nature of the pathogen that in its virulent phase I must be manipulated under biosafety level-3 conditions. Proteomic studies, in particular, have generated a vast amount of information concerning several aspects of the bacterium such as virulence factors, detection/diagnostic and immunogenic biomarkers, inter-/intraspecies variation, resistance to antibiotics, and secreted effector proteins with significant clinical impact. The phenomenon observed following the genomics era, that of generation and accumulation of huge amount of data that ultimately end up unexploited on several databases, begins to emerge in the proteomics field as well. This review will focus on the advances in the field of C. burnetii proteomics through MS, attempting in parallel to utilize some of the proteomics findings by suggesting future directions for the improvement of Q fever diagnosis and therapy.  相似文献   

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The purpose of this study is to establish a tumor marker that can be applied for the early detection and follow-up of oral cancer patients. Employing the proteomic approach using MALDI TOF-MS, 2-DE, patient's sera and culturing cell lines, the serum autoantibodies (autoAbs) were screened and the serum levels were estimated by ELISA. Targeting the tumor cell invasion into the surrounding stromal tissues, MRC-5 human fibroblasts were employed as the target cells and a mitochondrial membrane protein, sideroflexin 3 (SFXN3), was identified. The serum anti-SFXN3-autoAb levels elevated in patients with the oral squamous cell carcinoma significantly: with 77% sensitivity and 89% specificity against control samples. The serum anti-SFXN3-autoAb levels were mildly correlated with the primary tumor sizes, however, the levels were slightly highly elevated in T1 early cancer. An immunohistochemical analysis revealed that the SFXN3 protein is expressed in the stromal fibroblasts between the caner nests and also in the basal layer of the squamous epithelium. Changes in the serum anti-SFXN3-autoAb levels after therapy correlated with the clinical tumor burden. These findings demonstrated that the serum anti-SFXN3-autoAb is worthy of clinical evaluation as a potentially of the novel tumor maker for the early detection of oral squamous cell carcinoma.  相似文献   

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Circulating antibodies reflect a mirror view of invading antigens that are related to infection and cancer. This was recently exemplified by using serum antibodies to capture Streptococcus bovis antigens followed by MS to generate antigen profiles that were diagnostic for colon cancer. These bacterial antigen profiles have a high potential to aid in the immuno‐diagnosis of this disease, as the magnitude of the immune response to bacterial antigens is, in general, superior to the immune response against tumor (self) antigens. In this study, the identity of individual colon cancer‐associated streptococcal antigens was revealed by enrichment of these “diagnostic” antigens by selected patient antibodies followed by high‐accuracy nanoLC‐MS/MS peptide identification. This showed that both the histone‐like protein HlpA and the ribosomal protein Rp L7/L12 are members of the colon cancer‐associated S. bovis immunome. Both antigens also seem to belong to the group of anchorless surface proteins, like 14 additional proteins that were co‐identified in S. bovis cell wall extracts. Among these were the known streptococcal anchorless surface proteins GAPDH and Enolase. Taken together, these data show that shotgun immunoproteomics, combining immunocapture in‐line with LC MS/MS, is a convenient approach for the rapid identification of disease‐associated bacterial antigens.  相似文献   

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蛋白质组学的快速发展,特别是高通量技术的发展产生了大量的蛋白质相互作用数据,为人们从更深层次理解蛋白质之间的相互作用及其在复杂疾病的作用机理提供了基础.一个生物体内所有的蛋白质与蛋白质之间的相互作用组成的网络称为蛋白质网络.传统的研究多是基于静态的蛋白质网络模型.然而,由于蛋白质自身表达的动态性及蛋白质间相互作用的动态性,真实的蛋白质网络会随着时间和条件不断变化,与疾病的发生和发展有关的蛋白质功能模块也与这种动态变化密切相关.因此,研究者已经把注意力从关注蛋白质网络的静态属性转移到动态属性上,提出了一系列的动态蛋白质网络的构建方法.在介绍静态蛋白质网络的基础上,分类讨论了动态蛋白质网络的构建方法,将现有的动态蛋白质网络的构建方法归纳为基于蛋白质表达动态性的方法、基于多状态下表达及相关性变化的方法和基于时空动态变化的方法这3类:第1类体现的是蛋白质自身表达随时间演化的动态性,第2类则表现为不同条件下蛋白质之间表达相关性的改变,第3类则体现了蛋白质及蛋白质相互作用在时间和空间上的动态变化.然后,对动态蛋白质网络的蛋白质节点和相关子网络进行了动态分析并详细介绍了动态蛋白质网络在复杂疾病中的一些主流应用,如蛋白质复合物识别、蛋白质功能预测、生物标志物识别、疾病基因预测等.最后,对动态蛋白质网络所面临的挑战与未来的研究方向进行了探讨.  相似文献   

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In the post-genomic era, proteomics has achieved significant theoretical and practical advances with the development of high-throughput technologies. Especially the rapid accumulation of protein-protein interactions (PPIs) provides a foundation for constructing protein interaction networks (PINs), which can furnish a new perspective for understanding cellular organizations, processes, and functions at network level. In this paper, we present a comprehensive survey on three main characteristics of PINs: centrality, modularity, and dynamics. 1) Different centrality measures, which are used to calculate the importance of proteins, are summarized based on the structural characteristics of PINs or on the basis of its integrated biological information; 2) Different modularity definitions and various clustering algorithms for predicting protein complexes or identifying functional modules are introduced; 3) The dynamics of proteins, PPIs and sub-networks are discussed, respectively. Finally, the main applications of PINs in the complex diseases are reviewed, and the challenges and future research directions are also discussed.  相似文献   

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全基因组关联研究(GWAS)是在探究人类复杂疾病相关基因的重要方法,实用有效的算法是GWAS成功的关键,因此根据疾病模型生成模拟数据对GWAS算法进行比较测试具有重要的意义。模拟测试要求根据各种输入的控制量计算出疾病模型的相关参数,但是目前缺乏相关公开的算法。提出了一个求解这些参数的分支限界算法。大量实验测试表明该算法能快速精确地计算出疾病模型的相关参数,可用于搭建GWAS算法测试平台。  相似文献   

14.
生物免疫原理在入侵检测系统中的应用   总被引:2,自引:1,他引:2  
介绍生物免疫系统的免疫原理,提出一个基于人工免疫原理的入侵检测模型,重点分析模型"自我"和"非自我"的界定、检测规则和检测算法,提出基于阴性选择的检测器生成算法.  相似文献   

15.
人工免疫系统:理论与应用   总被引:10,自引:0,他引:10  
由生物引发的信息处理系统可分为:人工神经网络、进化计算和人工免疫系统(AIS).其中,神经网络和进化计算已被广泛地应用于各领域,而AIS由于其复杂性,应用相对较少.AIS实现一种由生物免疫系统启发的通过学习外界物质的自然防御机理的学习技术,提供了噪声忍耐、无教师学习、自组织、不需要反面例子、能明晰地表达学习的知识、具有内容可访记忆和能遗忘很少使用的信息等进化学习机理,结合了分类器、神经网络和机器推理等系统的一些优点,因此具有提供新颖的解决问题方法的潜力.为促使AIS更好地应用于科学和工程领域,本文系统地综述了AIS的最新研究成果,最后指出了其进一步研究的方向.  相似文献   

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To screen for autoantibodies associated with systemic lupus erythematosus (SLE), we used proteomic approaches combining 2-D PAGE and Western blot analysis, followed by protein identification by LC-MS/MS analysis, resulting in the identification of aldolase A as a novel autoantigen in SLE. ELISA showed the prevalence of anti-aldolase A antibodies to be 29.3% in SLE, 8.2% in rheumatoid arthritis, 18.1% in polymyositis and absent in healthy controls. Furthermore, 43.4% of SLE patients suffering from nephritis showed anti-aldolase A autoantibodies, which was significantly higher than the prevalence for those without nephritis (11.1%). In lupus nephritis, there are few reliable diagnostic methods, other than urinalysis. Therefore, these results indicate that autoantibodies against aldolase A may serve as an alternative clinical biomarker of SLE associated with nephritis.  相似文献   

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The prevalence of tomato leaf diseases should be diagnosed in early-stage to prevent spoilage of the entire field. Manually checking tomato diseases consumes more time and is labor-intensive. In modern agriculture, machine and deep learning-based disease identification techniques have been developed to effectively classify diseases. Most of the existing methods are inappropriate for horticulture due to their incompetence in handling the complex backgrounds of the image. In this article, a novel segmentation and classification algorithm is proposed for detecting tomato leaf diseases with complex background interference based on leaf segmentation fuzzy CNN (LSFCNN) and ant colony-based mask RCNN (AC-MRCNN). Foremostly the collected images are annotated and enhanced for further processing. Then the novel LSFCNN is implemented to separate the tomato leaf in a complex background. For classification, AC-MRCNN is developed, which masks the disease spot and recognizes the diseases. Herein ant colony optimization algorithm is utilized to optimize the mask RCNN to increase the flow of information and gradients of the network. Over 14,817 uniform and complex background images are collected to train the model. The proposed method is profoundly effective for quite challenging background leaf disease classification, with an accuracy of 97.66% of eight diseases and one healthy class.  相似文献   

19.
人工免疫系统的应用与发展   总被引:9,自引:0,他引:9  
在现代信息科学和生命科学相互交叉渗透的研究领域,由生物免疫系统启发的人工免疫系统(AIS)是继脑神经系统(神经网络)和遗传系统(进化计算)之后的又一个研究热点。该文首先简要介绍了生物免疫系统的特点,然后系统综述了国内外对人工免疫系统的最新研究和应用成果,最后展望了人工免疫系统进一步的研究方向。  相似文献   

20.
基于人工免疫系统的数据挖掘技术原理与应用   总被引:6,自引:0,他引:6  
该文首先对人工免疫系统的发展历史和自然免疫系统机制进行简要介绍,之后重点对人工免疫系统在数据挖掘领域中的原理与应用研究进行详细分析综述。主要分两个部分,第一部分是从数据挖掘的主要任务——聚类和分类角度阐述人工免疫系统应用现状,第二部分主要从数据挖掘对象子领域——网络数据挖掘和文件挖掘角度分析人工免疫系统的应用,同时对有代表性的方法及其改进过程进行了详细介绍,指出人工免疫数据挖掘技术中的优点和缺点。最后提出新的研究方向。  相似文献   

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