目的系统综述冠心病血瘀证基因组学研究的方法和内容。方法计算机检索Medline、Cochrane Central Register of Controlled Trials、中国知网、万方数据库,查找冠心病血瘀证基因组学的临床研究,按照制定的纳入排除标准,由2名研究人员独...目的系统综述冠心病血瘀证基因组学研究的方法和内容。方法计算机检索Medline、Cochrane Central Register of Controlled Trials、中国知网、万方数据库,查找冠心病血瘀证基因组学的临床研究,按照制定的纳入排除标准,由2名研究人员独立筛选文献,任何分歧通过协商一致或通过第3名研究人员来解决。结果最终纳入34项研究,其中与冠心病血瘀证密切相关的基因组学研究类型包括基因多态性、差异基因的表达、基因的甲基化修饰,涉及的生物学功能有血管内皮损伤、血液流变学改变、炎症反应与免疫调节、血管平滑肌增殖、血脂水平等,采用的技术方法有聚合酶链式反应(Polymerase chain reaction,PCR)、飞行时间质谱技术(Time-of-flight mass spectrometry,TOF-MS)、基因芯片杂交测序(Gene Chip)等。结论基因组学研究可阐明冠心病血瘀证的生物学基础,为冠心病血瘀证的病机演变提供更好的依据,更有助于从分子水平实现个体化治疗,从而进一步提高临床疗效。展开更多
Structural genomics (SG) is an international effort that aims at solving three-dimensional shapes of important biological macro-molecules with primary focus on proteins. One of the main bottlenecks in SG is the abilit...Structural genomics (SG) is an international effort that aims at solving three-dimensional shapes of important biological macro-molecules with primary focus on proteins. One of the main bottlenecks in SG is the ability to produce dif-fraction quality crystals for X-ray crystallogra-phy based protein structure determination. SG pipelines allow for certain flexibility in target selection which motivates development of in- silico methods for sequence-based prediction/ assessment of the protein crystallization pro-pensity. We overview existing SG databanks that are used to derive these predictive models and we discuss analytical results concerning protein sequence properties that were discov-ered to correlate with the ability to form crystals. We also contrast and empirically compare mo- dern sequence-based predictors of crystalliza-tion propensity including OB-Score, ParCrys, XtalPred and CRYSTALP2. Our analysis shows that these methods provide useful and compli-mentary predictions. Although their average ac- curacy is similar at around 70%, we show that application of a simple majority-vote based en-semble improves accuracy to almost 74%. The best improvements are achieved by combining XtalPred with CRYSTALP2 while OB-Score and ParCrys methods overlap to a larger extend, although they still complement the other two predictors. We also demonstrate that 90% of the protein chains can be correctly predicted by at least one of these methods, which suggests that more accurate ensembles could be built in the future. We believe that current protein crystalli-zation propensity predictors could provide useful input for the target selection procedures utilized by the SG centers.展开更多
The 14-3-3 protein family is among the most extensively studied, yet still largely mysterious protein families in mammals to date. As they are well recognized for their roles in apoptosis, cell cycle regulation, and p...The 14-3-3 protein family is among the most extensively studied, yet still largely mysterious protein families in mammals to date. As they are well recognized for their roles in apoptosis, cell cycle regulation, and proliferation in healthy cells, aberrant 14-3-3 expression has unsurprisingly emerged as instrumentalin the development of many cancers and in prognosis. Interestingly, while the seven known 14-3-3 isoforms in humans have many similar functions across cell types, evidence of isoform-specific functions and localization has been observed in both healthy and diseased cells The strikingly high similarity among 14-3-3 isoforms has made it difficult to delineate isoform-specific functions and for isoform-specific targeting. Here, we review our knowledge of 14-3-3 interactome（s） generated by high- throughput techniques, bioinformatics, structural genomics and chemical genornics and point out that integrating the information with molecular dynamics （MD） simulations may bring us new opportunity to the design of isoform-specific inhibitors, which can not only be used as powerful research tools for delineating distinct interactomes of individual 14-3-3 isoforms, but also can serve as potential new anti-cancer drugs that selectively target aberrant 14-3-3 isoform.展开更多
文摘目的系统综述冠心病血瘀证基因组学研究的方法和内容。方法计算机检索Medline、Cochrane Central Register of Controlled Trials、中国知网、万方数据库,查找冠心病血瘀证基因组学的临床研究,按照制定的纳入排除标准,由2名研究人员独立筛选文献,任何分歧通过协商一致或通过第3名研究人员来解决。结果最终纳入34项研究,其中与冠心病血瘀证密切相关的基因组学研究类型包括基因多态性、差异基因的表达、基因的甲基化修饰,涉及的生物学功能有血管内皮损伤、血液流变学改变、炎症反应与免疫调节、血管平滑肌增殖、血脂水平等,采用的技术方法有聚合酶链式反应(Polymerase chain reaction,PCR)、飞行时间质谱技术(Time-of-flight mass spectrometry,TOF-MS)、基因芯片杂交测序(Gene Chip)等。结论基因组学研究可阐明冠心病血瘀证的生物学基础,为冠心病血瘀证的病机演变提供更好的依据,更有助于从分子水平实现个体化治疗,从而进一步提高临床疗效。
文摘Structural genomics (SG) is an international effort that aims at solving three-dimensional shapes of important biological macro-molecules with primary focus on proteins. One of the main bottlenecks in SG is the ability to produce dif-fraction quality crystals for X-ray crystallogra-phy based protein structure determination. SG pipelines allow for certain flexibility in target selection which motivates development of in- silico methods for sequence-based prediction/ assessment of the protein crystallization pro-pensity. We overview existing SG databanks that are used to derive these predictive models and we discuss analytical results concerning protein sequence properties that were discov-ered to correlate with the ability to form crystals. We also contrast and empirically compare mo- dern sequence-based predictors of crystalliza-tion propensity including OB-Score, ParCrys, XtalPred and CRYSTALP2. Our analysis shows that these methods provide useful and compli-mentary predictions. Although their average ac- curacy is similar at around 70%, we show that application of a simple majority-vote based en-semble improves accuracy to almost 74%. The best improvements are achieved by combining XtalPred with CRYSTALP2 while OB-Score and ParCrys methods overlap to a larger extend, although they still complement the other two predictors. We also demonstrate that 90% of the protein chains can be correctly predicted by at least one of these methods, which suggests that more accurate ensembles could be built in the future. We believe that current protein crystalli-zation propensity predictors could provide useful input for the target selection procedures utilized by the SG centers.
文摘The 14-3-3 protein family is among the most extensively studied, yet still largely mysterious protein families in mammals to date. As they are well recognized for their roles in apoptosis, cell cycle regulation, and proliferation in healthy cells, aberrant 14-3-3 expression has unsurprisingly emerged as instrumentalin the development of many cancers and in prognosis. Interestingly, while the seven known 14-3-3 isoforms in humans have many similar functions across cell types, evidence of isoform-specific functions and localization has been observed in both healthy and diseased cells The strikingly high similarity among 14-3-3 isoforms has made it difficult to delineate isoform-specific functions and for isoform-specific targeting. Here, we review our knowledge of 14-3-3 interactome（s） generated by high- throughput techniques, bioinformatics, structural genomics and chemical genornics and point out that integrating the information with molecular dynamics （MD） simulations may bring us new opportunity to the design of isoform-specific inhibitors, which can not only be used as powerful research tools for delineating distinct interactomes of individual 14-3-3 isoforms, but also can serve as potential new anti-cancer drugs that selectively target aberrant 14-3-3 isoform.
