By integrating the concept of cooperative approach, an extension of the fast annealing coevolutionary algorithm is presented in this paper. It outperformed the original algorithm in the domain of function optimization...By integrating the concept of cooperative approach, an extension of the fast annealing coevolutionary algorithm is presented in this paper. It outperformed the original algorithm in the domain of function optimization, especially in terms of convergence rate. It was also applied to a real optimization problem, protein motif extraction. And a satisfactory result has been obtained with the accuracy of prediction achieving 67.0%, which is in agreement with the result in the PROSITE database.展开更多
Plasmodium (P.) falciparum is a pathogen that causes severe forms of malaria. Protein interactions have been shown to occur between P. falciparum and human erythrocytes in human blood. The Band 3 Anion Transporter (B3...Plasmodium (P.) falciparum is a pathogen that causes severe forms of malaria. Protein interactions have been shown to occur between P. falciparum and human erythrocytes in human blood. The Band 3 Anion Transporter (B3AT) protein is considered the main invasive pathway for the parasite in erythrocytes that causes clinical symptoms for malaria in humans. The interactions between P. falciparum parasites and erythrocytes along this receptor have previously been explored. Short linear motifs (SLIMs) are short linear mediator sequences that involve several biological processes, acting as mediators of protein interactions identifiable by computational tools such as SLiMFinder. For a given protein, the identification of SLIMs allows predicting its interactors. Using the SLIMs approach, protein-protein interaction network analyses between P. falciparum and its human host, were used to identify a tryptophan-rich protein, A5K5E5_PLAVS as an essential interactor of B3AT. To better understand the interaction mechanism, a guided protein-protein docking approach based on SLIM motifs was performed for human B3AT and A5K5E5_PLAVS. The highlights of this important interaction between P. falciparum and its human host have the potential to pave the way to identify new therapeutic candidates.展开更多
By integrating the cooperative approach with the fast annealing coevolutionary algorithm (FAEA), a so-called cooperative fast annealing coevolutionary algorithm (CFACA) is presented in this paper for the purpose of so...By integrating the cooperative approach with the fast annealing coevolutionary algorithm (FAEA), a so-called cooperative fast annealing coevolutionary algorithm (CFACA) is presented in this paper for the purpose of solving high-dimensional problems. After the partition of the search space in CFACA, each smaller one is then searched by a separate FAEA. The fitness function is evaluated by combining sub-solutions found by each of the FAEAs. It demonstrates that the CFACA outperforms the FAEA in the domain of function optimization, especially in terms of convergence rate. The current algorithm is also applied to a real optimization problem of protein motif extraction. And a satisfactory result has been obtained with the accuracy of prediction achieving 67.0%, which is in agreement with the result in the PROSITE database.展开更多
According to our previous study, saprophytic fungi Botrytis cinerea contained 579 predicted secretary proteins. Among them, we found that 122 of these proteins contained the highly conserved pathogenic-related host-ta...According to our previous study, saprophytic fungi Botrytis cinerea contained 579 predicted secretary proteins. Among them, we found that 122 of these proteins contained the highly conserved pathogenic-related host-targeting-motif RxLx within 100 residues adjacent to the signal peptide cleavage site. According to PEDNAT and COG of the GenBank database, the functions of this motif containing proteins included metabolism modification and cell secretion. We blasted them in GenBank and found 47.54% had highly conserved homologues in other species, among them 74.1% had putative functional domains. This suggests these proteins are presumably ancient and vertically transmitted within the species. Many of these domains belonged to proteins which played roles in the pathogenic process of other kinds of pathogens and some had already been proved to be pathogenic secretary proteins of Botrytis cinerea. So we postulated that proteins contained host-targeting-motif RxLx were candidates participating in the pathogenesis of Botrytis cinerea.展开更多
Lysin motif(LysM)-containing proteins(LYPs)are important pattern recognition receptors in plants.However,the evolutionary history and characteristics of LYP genes remain largely unclear in wheat.In this study,62 LYPs ...Lysin motif(LysM)-containing proteins(LYPs)are important pattern recognition receptors in plants.However,the evolutionary history and characteristics of LYP genes remain largely unclear in wheat.In this study,62 LYPs were identified at genome wide in wheat.Based on phylogenetic and domain analysis,wheat LYPs were classified into 6 subgroups(group LysMe,LysMn,LYP,LYK,LysMFbox).Syntenic analysis showed the evolution of LYP genes in wheat.RNA-seq data showed that 22 genes were not expressed at any tissue or stress stimulation period.Some LYP and LYK genes were tissue-or stage-specific.The majority of TaLYK5s,TaLYK6s,TaLYP2s and TaLysMns genes were induced under chitin,flg22 and fungal treatment.qRT-PCR analysis showed that 4 genes were upregulated during Puccinia triticina infection with a peak at 18 h post inoculation.Our findings suggested that wheat LYPs may have specific roles in response to fungal infection and provided insights into the function and characteristics of wheat LYP genes.展开更多
Phosphatidylinositol transfer proteins (PITP) are a family of monomeric proteins that bind and transfer phosphatidylinositol and phosphatidylcholine between membrane compartments. They are required for production of i...Phosphatidylinositol transfer proteins (PITP) are a family of monomeric proteins that bind and transfer phosphatidylinositol and phosphatidylcholine between membrane compartments. They are required for production of inositol and diacylglycerol second messengers, and are found in most metazoan organisms. While PITPs are known to carry out crucial cell-signaling roles in many organisms, the structure, function and evolution of the majority of family members remains unexplored;primarily because the ubiquity and diversity of the family thwarts traditional methods of global alignment. To surmount this obstacle, we instead took a novel approach, using MEME and a parsimony-based analysis to create a cladogram of conserved sequence motifs in 56 PITP family proteins from 26 species. In keeping with previous functional annotations, three clades were supported within our evolutionary analysis;two classes of soluble proteins and a class of membrane-associat- ed proteins. By, focusing on conserved regions, the analysis allowed for in depth queries regarding possible functional roles of PITP proteins in both intra- and extra- cellular signaling.展开更多
Protein tertiary structure is indispensible in revealing the biological functions of proteins. De novo perdition of protein tertiary structure is dependent on protein fold recognition. This study proposes a novel meth...Protein tertiary structure is indispensible in revealing the biological functions of proteins. De novo perdition of protein tertiary structure is dependent on protein fold recognition. This study proposes a novel method for prediction of protein fold types which takes primary sequence as input. The proposed method, PFP-RFSM, employs a random forest classifier and a comprehensive feature representation, including both sequence and predicted structure descriptors. Particularly, we propose a method for generation of features based on sequence motifs and those features are firstly employed in protein fold prediction. PFP-RFSM and ten representative protein fold predictors are validated in a benchmark dataset consisting of 27 fold types. Experiments demonstrate that PFP-RFSM outperforms all existing protein fold predictors and improves the success rates by 2%-14%. The results suggest sequence motifs are effective in classification and analysis of protein sequences.展开更多
Pancreatic ductal adenocarcinoma(PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significa...Pancreatic ductal adenocarcinoma(PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significantly enhanced efforts to prevent or intercept this cancer are clearly warranted. Oncogenic KRAS mutations are recognized initiating events in PDAC development, however, they are not entirely sufficient for the development of fully invasive PDAC.Additional genetic alterations and/or environmental, nutritional, and metabolic signals, as present in obesity, type-2 diabetes mellitus, and inflammation, are required for full PDAC formation. We hypothesize that oncogenic KRAS increases the intensity and duration of the growth-promoting signaling network.Recent exciting studies from different laboratories indicate that the activity of the transcriptional co-activators Yes-associated protein(YAP) and WW-domaincontaining transcriptional co-activator with PDZ-binding motif(TAZ) play a critical role in the promotion and maintenance of PDAC operating as key downstream target of KRAS signaling. While initially thought to be primarily an effector of the tumor-suppressive Hippo pathway, more recent studies revealed that YAP/TAZ subcellular localization and co-transcriptional activity is regulated by multiple upstream signals. Overall, YAP has emerged as a central node of transcriptional convergence in growth-promoting signaling in PDAC cells. Indeed, YAP expression is an independent unfavorable prognostic marker for overall survival of PDAC. In what follows, we will review studies implicating YAP/TAZ in pancreatic cancer development and consider different approaches to target these transcriptional regulators.展开更多
目的探讨核糖核酸结合基序蛋白45(RNA-binding motif protein 45,RBM45)在肝癌中的表达及其临床应用价值。方法应用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析RNA结合蛋白RBM45在肝癌中的表达,并关联临床资料及病理特征...目的探讨核糖核酸结合基序蛋白45(RNA-binding motif protein 45,RBM45)在肝癌中的表达及其临床应用价值。方法应用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析RNA结合蛋白RBM45在肝癌中的表达,并关联临床资料及病理特征进行统计学分析。运用基因富集分析软件GSEA对肝癌组织中与RBM45相关的基因进行KEGG信号通路富集分析。结果与癌旁组织相比,肝癌组织中RBM45表达明显升高(P<0.001),且RBM45表达水平与患者临床分期、肿瘤分级及预后均显著相关(P<0.05),通过构建单变量和多变量COX风险回归模型分析RBM45表达与临床资料的相关性,结果表明RBM45可做为肝癌患者独立预后的危险因素(HR:2.75695%CI:1.785-4.255,P=4.813e-06);KEGG富集分析显示,RBM45可能与细胞周期、卵母细胞减数分裂、泛素介导的蛋白水解等信号通路密切相关。结论RBM45在肝癌组织中高表达,且其高表达的患者预后较差;RBM45表达可作为肝癌患者预后判断的独立标志物。展开更多
基金This work was supported by the National Natural Science Foundation of China （No.20475068, 20575082） the Natural Science Foundation of Guangdong Province （No.031577） the Scientific Technology Project of Guangdong Province （No.2005B30101003）.
文摘By integrating the concept of cooperative approach, an extension of the fast annealing coevolutionary algorithm is presented in this paper. It outperformed the original algorithm in the domain of function optimization, especially in terms of convergence rate. It was also applied to a real optimization problem, protein motif extraction. And a satisfactory result has been obtained with the accuracy of prediction achieving 67.0%, which is in agreement with the result in the PROSITE database.
文摘Plasmodium (P.) falciparum is a pathogen that causes severe forms of malaria. Protein interactions have been shown to occur between P. falciparum and human erythrocytes in human blood. The Band 3 Anion Transporter (B3AT) protein is considered the main invasive pathway for the parasite in erythrocytes that causes clinical symptoms for malaria in humans. The interactions between P. falciparum parasites and erythrocytes along this receptor have previously been explored. Short linear motifs (SLIMs) are short linear mediator sequences that involve several biological processes, acting as mediators of protein interactions identifiable by computational tools such as SLiMFinder. For a given protein, the identification of SLIMs allows predicting its interactors. Using the SLIMs approach, protein-protein interaction network analyses between P. falciparum and its human host, were used to identify a tryptophan-rich protein, A5K5E5_PLAVS as an essential interactor of B3AT. To better understand the interaction mechanism, a guided protein-protein docking approach based on SLIM motifs was performed for human B3AT and A5K5E5_PLAVS. The highlights of this important interaction between P. falciparum and its human host have the potential to pave the way to identify new therapeutic candidates.
基金the National Natural Science Foundation of China (Grant Nos. 20475068 and 20575082)the Natural Science Foundation of Guangdong Province (Grant No. 031577)the Scientific Technology Project of Guangdong Province (Grant No. 2005B30101003)
文摘By integrating the cooperative approach with the fast annealing coevolutionary algorithm (FAEA), a so-called cooperative fast annealing coevolutionary algorithm (CFACA) is presented in this paper for the purpose of solving high-dimensional problems. After the partition of the search space in CFACA, each smaller one is then searched by a separate FAEA. The fitness function is evaluated by combining sub-solutions found by each of the FAEAs. It demonstrates that the CFACA outperforms the FAEA in the domain of function optimization, especially in terms of convergence rate. The current algorithm is also applied to a real optimization problem of protein motif extraction. And a satisfactory result has been obtained with the accuracy of prediction achieving 67.0%, which is in agreement with the result in the PROSITE database.
基金Supported by Project of Kunming University (YJL11014)
文摘According to our previous study, saprophytic fungi Botrytis cinerea contained 579 predicted secretary proteins. Among them, we found that 122 of these proteins contained the highly conserved pathogenic-related host-targeting-motif RxLx within 100 residues adjacent to the signal peptide cleavage site. According to PEDNAT and COG of the GenBank database, the functions of this motif containing proteins included metabolism modification and cell secretion. We blasted them in GenBank and found 47.54% had highly conserved homologues in other species, among them 74.1% had putative functional domains. This suggests these proteins are presumably ancient and vertically transmitted within the species. Many of these domains belonged to proteins which played roles in the pathogenic process of other kinds of pathogens and some had already been proved to be pathogenic secretary proteins of Botrytis cinerea. So we postulated that proteins contained host-targeting-motif RxLx were candidates participating in the pathogenesis of Botrytis cinerea.
基金supported by National Natural Science Foundation of China(Grant No.31801693)National Natural Fund Cultivation Project of Shanxi Academy of Agricultural Sciences(Grant No.YGJPY1902).
文摘Lysin motif(LysM)-containing proteins(LYPs)are important pattern recognition receptors in plants.However,the evolutionary history and characteristics of LYP genes remain largely unclear in wheat.In this study,62 LYPs were identified at genome wide in wheat.Based on phylogenetic and domain analysis,wheat LYPs were classified into 6 subgroups(group LysMe,LysMn,LYP,LYK,LysMFbox).Syntenic analysis showed the evolution of LYP genes in wheat.RNA-seq data showed that 22 genes were not expressed at any tissue or stress stimulation period.Some LYP and LYK genes were tissue-or stage-specific.The majority of TaLYK5s,TaLYK6s,TaLYP2s and TaLysMns genes were induced under chitin,flg22 and fungal treatment.qRT-PCR analysis showed that 4 genes were upregulated during Puccinia triticina infection with a peak at 18 h post inoculation.Our findings suggested that wheat LYPs may have specific roles in response to fungal infection and provided insights into the function and characteristics of wheat LYP genes.
文摘Phosphatidylinositol transfer proteins (PITP) are a family of monomeric proteins that bind and transfer phosphatidylinositol and phosphatidylcholine between membrane compartments. They are required for production of inositol and diacylglycerol second messengers, and are found in most metazoan organisms. While PITPs are known to carry out crucial cell-signaling roles in many organisms, the structure, function and evolution of the majority of family members remains unexplored;primarily because the ubiquity and diversity of the family thwarts traditional methods of global alignment. To surmount this obstacle, we instead took a novel approach, using MEME and a parsimony-based analysis to create a cladogram of conserved sequence motifs in 56 PITP family proteins from 26 species. In keeping with previous functional annotations, three clades were supported within our evolutionary analysis;two classes of soluble proteins and a class of membrane-associat- ed proteins. By, focusing on conserved regions, the analysis allowed for in depth queries regarding possible functional roles of PITP proteins in both intra- and extra- cellular signaling.
文摘Protein tertiary structure is indispensible in revealing the biological functions of proteins. De novo perdition of protein tertiary structure is dependent on protein fold recognition. This study proposes a novel method for prediction of protein fold types which takes primary sequence as input. The proposed method, PFP-RFSM, employs a random forest classifier and a comprehensive feature representation, including both sequence and predicted structure descriptors. Particularly, we propose a method for generation of features based on sequence motifs and those features are firstly employed in protein fold prediction. PFP-RFSM and ten representative protein fold predictors are validated in a benchmark dataset consisting of 27 fold types. Experiments demonstrate that PFP-RFSM outperforms all existing protein fold predictors and improves the success rates by 2%-14%. The results suggest sequence motifs are effective in classification and analysis of protein sequences.
文摘Pancreatic ductal adenocarcinoma(PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significantly enhanced efforts to prevent or intercept this cancer are clearly warranted. Oncogenic KRAS mutations are recognized initiating events in PDAC development, however, they are not entirely sufficient for the development of fully invasive PDAC.Additional genetic alterations and/or environmental, nutritional, and metabolic signals, as present in obesity, type-2 diabetes mellitus, and inflammation, are required for full PDAC formation. We hypothesize that oncogenic KRAS increases the intensity and duration of the growth-promoting signaling network.Recent exciting studies from different laboratories indicate that the activity of the transcriptional co-activators Yes-associated protein(YAP) and WW-domaincontaining transcriptional co-activator with PDZ-binding motif(TAZ) play a critical role in the promotion and maintenance of PDAC operating as key downstream target of KRAS signaling. While initially thought to be primarily an effector of the tumor-suppressive Hippo pathway, more recent studies revealed that YAP/TAZ subcellular localization and co-transcriptional activity is regulated by multiple upstream signals. Overall, YAP has emerged as a central node of transcriptional convergence in growth-promoting signaling in PDAC cells. Indeed, YAP expression is an independent unfavorable prognostic marker for overall survival of PDAC. In what follows, we will review studies implicating YAP/TAZ in pancreatic cancer development and consider different approaches to target these transcriptional regulators.
文摘目的探讨核糖核酸结合基序蛋白45(RNA-binding motif protein 45,RBM45)在肝癌中的表达及其临床应用价值。方法应用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析RNA结合蛋白RBM45在肝癌中的表达,并关联临床资料及病理特征进行统计学分析。运用基因富集分析软件GSEA对肝癌组织中与RBM45相关的基因进行KEGG信号通路富集分析。结果与癌旁组织相比,肝癌组织中RBM45表达明显升高(P<0.001),且RBM45表达水平与患者临床分期、肿瘤分级及预后均显著相关(P<0.05),通过构建单变量和多变量COX风险回归模型分析RBM45表达与临床资料的相关性,结果表明RBM45可做为肝癌患者独立预后的危险因素(HR:2.75695%CI:1.785-4.255,P=4.813e-06);KEGG富集分析显示,RBM45可能与细胞周期、卵母细胞减数分裂、泛素介导的蛋白水解等信号通路密切相关。结论RBM45在肝癌组织中高表达,且其高表达的患者预后较差;RBM45表达可作为肝癌患者预后判断的独立标志物。
