Systemic lupus erythematosus （SLE） is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technol...Systemic lupus erythematosus （SLE） is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components （nucleic acids and associated proteins）, cytoplas- mic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epi- topes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection.展开更多
The development of cancer is a pathological process involving multiple environmental carcinogenic factors and genetic alterations.For decades,cancer researchers have focused on genomic and transcriptomic analyses.The ...The development of cancer is a pathological process involving multiple environmental carcinogenic factors and genetic alterations.For decades,cancer researchers have focused on genomic and transcriptomic analyses.The completion of the Human Genome Project has opened the door to the post-genome era and oncoproteomics.Proteins play a critical role in tumorigenesis and influence the differences between normal cells and malignant cells.This report proposes the concept that cancer is a proteomic disease.This concept is based on examining protein expression profiles,post-translational modifications,and protein-protein interactions in carcinogenesis using recent advances in comparative,functional and structural proteomics.This approach provides a new way of viewing carcinogenesis,presents new clues in biomarker discovery for cancer diagnosis and therapy,and reveals important scientific findings and their significance to clinical applications.展开更多
目的应用液体蛋白芯片飞行时间质谱系统分析2型糖尿病性视网膜病变的血清蛋白质表达谱,寻找具有潜在诊断意义的血清标志物,以便于糖尿病视网膜病变的早期诊断。方法收集2型糖尿病但不伴糖尿病视网膜病变的患者24例,2型糖尿病合并糖尿病...目的应用液体蛋白芯片飞行时间质谱系统分析2型糖尿病性视网膜病变的血清蛋白质表达谱,寻找具有潜在诊断意义的血清标志物,以便于糖尿病视网膜病变的早期诊断。方法收集2型糖尿病但不伴糖尿病视网膜病变的患者24例,2型糖尿病合并糖尿病视网膜病变的患者21例血清样本,通过Clin Prot磁珠纯化、飞行时间质谱分析、Clin Pro Tools生物信息学方法研究糖尿病视网膜病变的血清蛋白表达谱。结果质荷比(m/z)为1945.53的蛋白峰能较好地鉴别糖尿病性视网膜病变。其识别率和预测能力分别为88.57%和82.08%。结论以液体蛋白芯片飞行时间质谱系统工具研究蛋白表达谱,筛选得到的质荷比为1945.53的蛋白可能为潜在的2型糖尿病性视网膜病变的血清标志物。展开更多
In this study, we present a constructive algorithm for training cooperative support vector machine ensembles （CSVMEs）. CSVME combines ensemble architecture design with cooperative training for individual SVMs in ens...In this study, we present a constructive algorithm for training cooperative support vector machine ensembles （CSVMEs）. CSVME combines ensemble architecture design with cooperative training for individual SVMs in ensembles. Unlike most previous studies on training ensembles, CSVME puts emphasis on both accuracy and collaboration among individual SVMs in an ensemble. A group of SVMs selected on the basis of recursive classifier elimination is used in CSVME, and the number of the individual SVMs selected to construct CSVME is determined by 10-fold cross-validation. This kind of SVME has been tested on two ovarian cancer datasets previously obtained by proteomic mass spectrometry. By combining several individual SVMs, the proposed method achieves better performance than the SVME of all base SVMs.展开更多
Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies....Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies. The precise determination of the specific composition of protein complexes, especially using scalable and high-throughput methods, represents a systematic approach toward revealing particular cellular biological functions. In this regard, the direct profiling protein-protein interactions (PPIs) represent an efficient way to dissect functional pathways for revealing novel protein functions. In this review, we illustrate the technological evolution for the large-scale and precise identification of PPIs toward higher physiologically relevant accuracy. These techniques aim at improving the efficiency of complex pull-down, the signal specificity and accuracy in distinguishing specific PPIs, and the accuracy of identifying physiological relevant PPIs. A newly developed streamline proteomic approach for mapping the binary relationship of PPIs in a protein complex is introduced.展开更多
Small ubiquitin-like modifiers(SUMOs)are protein modifiers that can form polymeric chains.They are important signals in cellular processes,and their study and profiling require the development of molecular tools.Herei...Small ubiquitin-like modifiers(SUMOs)are protein modifiers that can form polymeric chains.They are important signals in cellular processes,and their study and profiling require the development of molecular tools.Herein,the authors have reported an efficient chemical protein synthesis approach for the generation of dimeric SUMO-2-based photoaffinity probes through the ligation of four readily synthesizable peptides.Proteomic studies using this diSUMO-2 probe on HeLa cell nuclear lysate found it to capture a significantly different selection of proteins compared with its monoSUMO counterparts.This resulted in the identification of several previously unknown SUMO chain-specific interacting proteins such as 40S ribosomal protein S3,which showed a significantly higher affinity for polySUMO chains than monomeric SUMO.Collectively,these results emphasize the need to develop SUMO chain-based probes in other species,and to shed light on the important role of polySUMOylation in diseases.展开更多
目的:探讨用蛋白质芯片技术筛选春季卡他性结膜炎(vernal keratoconjunctivis,VKC)患者泪液中蛋白质表达谱,寻找泪液中的标志性蛋白。方法:采用表面增强激光解离飞行时间质谱技术(surface-enhanced la-ser desorption/ionization time o...目的:探讨用蛋白质芯片技术筛选春季卡他性结膜炎(vernal keratoconjunctivis,VKC)患者泪液中蛋白质表达谱,寻找泪液中的标志性蛋白。方法:采用表面增强激光解离飞行时间质谱技术(surface-enhanced la-ser desorption/ionization time of flight mass spectrometry,SELDI-TOF-MS),运用CM10蛋白质芯片检测66例VKC患者和62例正常对照组泪液中蛋白质谱,获得的蛋白质谱采用Biomarker Wizard软件分析,初步筛选蛋白质峰,结合生物信息学的支持向量机(support vector machines,SVM)方法建立并测试VKC患者泪液中的蛋白质指纹图谱模型。结果:在芯片上捕获到145种蛋白质,用质谱仪筛选出VKC患者与正常对照组相比的23种差异蛋白,从中再次筛选出3种蛋白质组成VKC的蛋白质谱最优化模型,VKC患者泪液中质荷比(m/z)分别为2024.3,6630.2和8598.9的3种蛋白质表达上调。模型经三倍交叉验证后用盲法测定,其敏感性和特异性分别为90.91%和93.55%,阳性预测值为93.75%。结论:蛋白质芯片技术可快速、有效地筛选出VKC患者泪液差异蛋白,结合SVM可建立一个由3种蛋白质组成的蛋白质指纹图谱模型,可对VKC做很好的诊断预测,对这3种蛋白质尤其是m/z为2024.8的蛋白质进行研究,有助于VKC病因学进展及诊断标记物的发现。展开更多
目的探讨用蛋白质芯片技术筛选精索静脉曲张患者精浆中蛋白质表达谱,寻找差异蛋白。方法采用表面增强激光解离飞行时间质谱技术(surface-enhanced laser desorption/ionization time of flight mass spectrometry,SELDI-TOF-MS),运用CM1...目的探讨用蛋白质芯片技术筛选精索静脉曲张患者精浆中蛋白质表达谱,寻找差异蛋白。方法采用表面增强激光解离飞行时间质谱技术(surface-enhanced laser desorption/ionization time of flight mass spectrometry,SELDI-TOF-MS),运用CM10蛋白质芯片检测30例精索静脉曲张患者和30例正常对照精浆中蛋白质谱,获得的蛋白质谱采用Biomark-er Wizard软件分析,初步筛选蛋白质峰,结合生物信息学的支持向量机(support vector machines,SVM)方法建立并测试精索静脉曲张患者精浆中的蛋白质指纹图谱。结果在芯片上捕获到163种蛋白质,用质谱仪筛选出精索静脉曲张患者与正常对照组相比的16种差异蛋白,其中有3个蛋存在显著性差异。结论精索静脉曲张患者与健康者精浆中存在较多差异蛋白质,本研究对进一步探索精索静脉曲张的病因及其临床治疗具有重要意义。展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81270852)
文摘Systemic lupus erythematosus （SLE） is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components （nucleic acids and associated proteins）, cytoplas- mic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epi- topes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection.
基金supported by the National Basic Research Program of China (Grant Nos.2001CB510207 and 2011CB910704)the National Natural Science Foundation of China (Grant Nos.30800419,30973289 and 30972970)+1 种基金Science and Technology Foundation of Hengyang (Grant No.2010kj10)grants for Outstanding Scholars of New Era from Ministry of Education of China (Grant No.NCET-07-0861)
文摘The development of cancer is a pathological process involving multiple environmental carcinogenic factors and genetic alterations.For decades,cancer researchers have focused on genomic and transcriptomic analyses.The completion of the Human Genome Project has opened the door to the post-genome era and oncoproteomics.Proteins play a critical role in tumorigenesis and influence the differences between normal cells and malignant cells.This report proposes the concept that cancer is a proteomic disease.This concept is based on examining protein expression profiles,post-translational modifications,and protein-protein interactions in carcinogenesis using recent advances in comparative,functional and structural proteomics.This approach provides a new way of viewing carcinogenesis,presents new clues in biomarker discovery for cancer diagnosis and therapy,and reveals important scientific findings and their significance to clinical applications.
文摘目的应用液体蛋白芯片飞行时间质谱系统分析2型糖尿病性视网膜病变的血清蛋白质表达谱,寻找具有潜在诊断意义的血清标志物,以便于糖尿病视网膜病变的早期诊断。方法收集2型糖尿病但不伴糖尿病视网膜病变的患者24例,2型糖尿病合并糖尿病视网膜病变的患者21例血清样本,通过Clin Prot磁珠纯化、飞行时间质谱分析、Clin Pro Tools生物信息学方法研究糖尿病视网膜病变的血清蛋白表达谱。结果质荷比(m/z)为1945.53的蛋白峰能较好地鉴别糖尿病性视网膜病变。其识别率和预测能力分别为88.57%和82.08%。结论以液体蛋白芯片飞行时间质谱系统工具研究蛋白表达谱,筛选得到的质荷比为1945.53的蛋白可能为潜在的2型糖尿病性视网膜病变的血清标志物。
基金partly supported by the National Natural Science Foundation of China (No.60574019 and 60474045)the National Basic Research Program(973 Program)of China(No.2002CB312200)+2 种基金the Key Technologies R&D Program of Zhejiang Province (No.2005C21087)the Academician Foundation of Zhejiang Province(No.2005A1001-13)the Center for Bioinformatics Program Grant of Harvard Center of Neurodegeneration and Repair,Harvard Medical School,Boston,USA.
文摘In this study, we present a constructive algorithm for training cooperative support vector machine ensembles （CSVMEs）. CSVME combines ensemble architecture design with cooperative training for individual SVMs in ensembles. Unlike most previous studies on training ensembles, CSVME puts emphasis on both accuracy and collaboration among individual SVMs in an ensemble. A group of SVMs selected on the basis of recursive classifier elimination is used in CSVME, and the number of the individual SVMs selected to construct CSVME is determined by 10-fold cross-validation. This kind of SVME has been tested on two ovarian cancer datasets previously obtained by proteomic mass spectrometry. By combining several individual SVMs, the proposed method achieves better performance than the SVME of all base SVMs.
基金support from the Shanghai Science and Technology Development Program (Grant Nos. 03DZ14024 & 07ZR14010)the 863 High Technology Foundation of China (Grant No. 2006AA02A310)+1 种基金US NIH 1R01AI064806-01A2, 5R21DK082706U.S. Department of Energy, the Office of Science (BER) (Grant No. DE-FG02- 07ER64422)
文摘Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies. The precise determination of the specific composition of protein complexes, especially using scalable and high-throughput methods, represents a systematic approach toward revealing particular cellular biological functions. In this regard, the direct profiling protein-protein interactions (PPIs) represent an efficient way to dissect functional pathways for revealing novel protein functions. In this review, we illustrate the technological evolution for the large-scale and precise identification of PPIs toward higher physiologically relevant accuracy. These techniques aim at improving the efficiency of complex pull-down, the signal specificity and accuracy in distinguishing specific PPIs, and the accuracy of identifying physiological relevant PPIs. A newly developed streamline proteomic approach for mapping the binary relationship of PPIs in a protein complex is introduced.
基金This study was supported by the National Key R&D Program of China(nos.2017YFA0505200 and 2017YFA0505400)the National Natural Science Foundation of China(nos.91753205,21877024,21977089,81621002,and 21621003)the Fundamental Research Funds for the Central Universities(no.JZ2019HGPB0105).
文摘Small ubiquitin-like modifiers(SUMOs)are protein modifiers that can form polymeric chains.They are important signals in cellular processes,and their study and profiling require the development of molecular tools.Herein,the authors have reported an efficient chemical protein synthesis approach for the generation of dimeric SUMO-2-based photoaffinity probes through the ligation of four readily synthesizable peptides.Proteomic studies using this diSUMO-2 probe on HeLa cell nuclear lysate found it to capture a significantly different selection of proteins compared with its monoSUMO counterparts.This resulted in the identification of several previously unknown SUMO chain-specific interacting proteins such as 40S ribosomal protein S3,which showed a significantly higher affinity for polySUMO chains than monomeric SUMO.Collectively,these results emphasize the need to develop SUMO chain-based probes in other species,and to shed light on the important role of polySUMOylation in diseases.
文摘目的:探讨用蛋白质芯片技术筛选春季卡他性结膜炎(vernal keratoconjunctivis,VKC)患者泪液中蛋白质表达谱,寻找泪液中的标志性蛋白。方法:采用表面增强激光解离飞行时间质谱技术(surface-enhanced la-ser desorption/ionization time of flight mass spectrometry,SELDI-TOF-MS),运用CM10蛋白质芯片检测66例VKC患者和62例正常对照组泪液中蛋白质谱,获得的蛋白质谱采用Biomarker Wizard软件分析,初步筛选蛋白质峰,结合生物信息学的支持向量机(support vector machines,SVM)方法建立并测试VKC患者泪液中的蛋白质指纹图谱模型。结果:在芯片上捕获到145种蛋白质,用质谱仪筛选出VKC患者与正常对照组相比的23种差异蛋白,从中再次筛选出3种蛋白质组成VKC的蛋白质谱最优化模型,VKC患者泪液中质荷比(m/z)分别为2024.3,6630.2和8598.9的3种蛋白质表达上调。模型经三倍交叉验证后用盲法测定,其敏感性和特异性分别为90.91%和93.55%,阳性预测值为93.75%。结论:蛋白质芯片技术可快速、有效地筛选出VKC患者泪液差异蛋白,结合SVM可建立一个由3种蛋白质组成的蛋白质指纹图谱模型,可对VKC做很好的诊断预测,对这3种蛋白质尤其是m/z为2024.8的蛋白质进行研究,有助于VKC病因学进展及诊断标记物的发现。
文摘目的探讨用蛋白质芯片技术筛选精索静脉曲张患者精浆中蛋白质表达谱,寻找差异蛋白。方法采用表面增强激光解离飞行时间质谱技术(surface-enhanced laser desorption/ionization time of flight mass spectrometry,SELDI-TOF-MS),运用CM10蛋白质芯片检测30例精索静脉曲张患者和30例正常对照精浆中蛋白质谱,获得的蛋白质谱采用Biomark-er Wizard软件分析,初步筛选蛋白质峰,结合生物信息学的支持向量机(support vector machines,SVM)方法建立并测试精索静脉曲张患者精浆中的蛋白质指纹图谱。结果在芯片上捕获到163种蛋白质,用质谱仪筛选出精索静脉曲张患者与正常对照组相比的16种差异蛋白,其中有3个蛋存在显著性差异。结论精索静脉曲张患者与健康者精浆中存在较多差异蛋白质,本研究对进一步探索精索静脉曲张的病因及其临床治疗具有重要意义。
