Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile prote...Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. Methods: Bile samples from 20 patients(10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling(TMT) and liquid chromatography-tandem mass spectrometry(LC-MS/MS), followed by further bioinformatic analysis. Results: Among the differentially expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor(PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APO A-Ⅰ and APO A-Ⅱ, were confirmed using enzyme-linked immunosorbent assay. Conclusions: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.展开更多
Development of new technologies for evaluating genetically modiifed （GM） crops has revealed that there are unintended insertions and expression changes in GM crops. Proifling techniques are non-targeted approaches a...Development of new technologies for evaluating genetically modiifed （GM） crops has revealed that there are unintended insertions and expression changes in GM crops. Proifling techniques are non-targeted approaches and are capable of detecting more unintended changes in GM crops. Here, we report the application of a comparative proteomic approach to investigate the protein proifle differences between a GM rice line, which has a lysine-rich protein gene, and its non-transgenic parental line. Proteome analysis by two-dimensional gel electrophoresis （2-DE） and mass spectrum analysis of the seeds identiifed 22 differentially expressed protein spots. Apart from a number of glutelins that were detected as targeted proteins in the GM line, the majority of the other changed proteins were involved in carbohydrate metabolism, protein synthesis and stress responses. These results indicated that the altered proteins were not associated with plant allergens or toxicity.展开更多
Complement (C) activation-related hypersensitivity reactions (HSRs) represent an unsolved adverse immune effect of many i.v. administered “nanomedicines”, such as liposomal doxorubicin (Doxil/Caelyx). Because these ...Complement (C) activation-related hypersensitivity reactions (HSRs) represent an unsolved adverse immune effect of many i.v. administered “nanomedicines”, such as liposomal doxorubicin (Doxil/Caelyx). Because these pseudoallergic reactions can be severe or even lethal, it is an important clinical objective to find biomarkers for proneness for C activation by reactogenic nanoparticles that will allow the prediction of in vivo reactions by in vitro assays. With this goal in mind we identified a normal human blood donor who consistently showed high sensitivity to Caelyx-induced C activation in vitro, whose plasma (Caelyx sensitive plasma, CSP) was subjected to proteome profiling with a library of human plasma proteome specific mAbs. The chip (PlasmaScan-380TM) contained 380 non redundant (with respect to epitopes) mAbs. The analysis revealed 8 proteins that were differentially represented in CSP in comparison with Caelyx-insensitive control plasma. These proteins were identified by mass spectrometry and Western blot analyses to represent factor H (decreased in CSP), factor H related protein, serum amyloid P component, fibronectin, complement component C4, Apo B100, prothrombin and alpha-2-HS glycoprotein (all increased in CSP). Some of these protein changes are consistent with proneness for increased C activation, suggesting the potential use of this method in the search for biomarkers for liposome-induced or other types of nanomedicine-induced HSRs.展开更多
Objective This study was mainly focused on study of the proteome profile change between exposure to 1-Bromopropane(1-BP)and 1-BP poisoning.Methods The samples of serums from exposure to 1-BP and 1-BP poisoning were co...Objective This study was mainly focused on study of the proteome profile change between exposure to 1-Bromopropane(1-BP)and 1-BP poisoning.Methods The samples of serums from exposure to 1-BP and 1-BP poisoning were collected and analyzed through Label展开更多
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
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
基金Public Welfare Re-search Fund of Huzhou City(2018GYB60).
文摘Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. Methods: Bile samples from 20 patients(10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling(TMT) and liquid chromatography-tandem mass spectrometry(LC-MS/MS), followed by further bioinformatic analysis. Results: Among the differentially expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor(PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APO A-Ⅰ and APO A-Ⅱ, were confirmed using enzyme-linked immunosorbent assay. Conclusions: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.
基金supported by the National Major Special Project for the Development of Transgenic OrganismsChina(2009ZX-08011-003B)+2 种基金the Jiangsu Province Qing Lan Project for Young and Middle-Aged Academic LeadersChina and the Jiangsu Province Qing Lan Project for Outstanding Scientific and Technological Innovation TeamChina
文摘Development of new technologies for evaluating genetically modiifed （GM） crops has revealed that there are unintended insertions and expression changes in GM crops. Proifling techniques are non-targeted approaches and are capable of detecting more unintended changes in GM crops. Here, we report the application of a comparative proteomic approach to investigate the protein proifle differences between a GM rice line, which has a lysine-rich protein gene, and its non-transgenic parental line. Proteome analysis by two-dimensional gel electrophoresis （2-DE） and mass spectrum analysis of the seeds identiifed 22 differentially expressed protein spots. Apart from a number of glutelins that were detected as targeted proteins in the GM line, the majority of the other changed proteins were involved in carbohydrate metabolism, protein synthesis and stress responses. These results indicated that the altered proteins were not associated with plant allergens or toxicity.
文摘Complement (C) activation-related hypersensitivity reactions (HSRs) represent an unsolved adverse immune effect of many i.v. administered “nanomedicines”, such as liposomal doxorubicin (Doxil/Caelyx). Because these pseudoallergic reactions can be severe or even lethal, it is an important clinical objective to find biomarkers for proneness for C activation by reactogenic nanoparticles that will allow the prediction of in vivo reactions by in vitro assays. With this goal in mind we identified a normal human blood donor who consistently showed high sensitivity to Caelyx-induced C activation in vitro, whose plasma (Caelyx sensitive plasma, CSP) was subjected to proteome profiling with a library of human plasma proteome specific mAbs. The chip (PlasmaScan-380TM) contained 380 non redundant (with respect to epitopes) mAbs. The analysis revealed 8 proteins that were differentially represented in CSP in comparison with Caelyx-insensitive control plasma. These proteins were identified by mass spectrometry and Western blot analyses to represent factor H (decreased in CSP), factor H related protein, serum amyloid P component, fibronectin, complement component C4, Apo B100, prothrombin and alpha-2-HS glycoprotein (all increased in CSP). Some of these protein changes are consistent with proneness for increased C activation, suggesting the potential use of this method in the search for biomarkers for liposome-induced or other types of nanomedicine-induced HSRs.
文摘Objective This study was mainly focused on study of the proteome profile change between exposure to 1-Bromopropane(1-BP)and 1-BP poisoning.Methods The samples of serums from exposure to 1-BP and 1-BP poisoning were collected and analyzed through Label
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.
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.
