The ability to knockdown the expression of an endogenous gene by RNAi has emerged as a powerful strategy for the rapid identification of specific gene functions. Vector-based constitutive expression of shRNA can resul...The ability to knockdown the expression of an endogenous gene by RNAi has emerged as a powerful strategy for the rapid identification of specific gene functions. Vector-based constitutive expression of shRNA can result in stable and efficient knockdown of target genes. However, constitutive expression of shRNA imposes major limitations when analyzing the fimction of genes whose expression is vital for the survival of an organism. Inducible RNAi systems can circumvent this limitation by enabling the inhibition of expression of an essential gene only when the inducing agent is present, and the level of knockdown of the essential gene can be controlled and adjusted by the concentration of inducing agent. In this review, we briefly summarize the recent development of various inducible RNAi systems and their potential applications in drug target validation.展开更多
MicroRNAs (miRNAs) are a group of regulatory RNAs that regulate gene expression post-transcriptionally by the degradation or translational inhibition of their target messenger RNAs (mRNAs). Regulation is accomplis...MicroRNAs (miRNAs) are a group of regulatory RNAs that regulate gene expression post-transcriptionally by the degradation or translational inhibition of their target messenger RNAs (mRNAs). Regulation is accomplished when the 22-25 nucleotide miRNAs bind to complementary sequences in the 3'-untranslated regions (UTR). One barrier to miRNA research is to find target genes. Although computational target predictions have shed light on important aspects of microRNA target recognition, questions remain concerning the rates of false positives. In addition, we do not completely understand how microRNAs can recognize and regulate their targets. As such, experimental positive predictions and allow for an unbiased stu ap dy proaches are required, which can reflect in vivo processes, eliminating false of microRNA target recognition. In this review, we summarized experimental approaches that have been described for the identification and validation of mRNA targets associated with specific miRNAs.展开更多
Radar Maneuvering Targets Tracking(RMTT) in clutter is a quite challenging issue due to the errors in the models and the varying dynamics of the processes. Modern radar tracking system calls for the adaptive signal an...Radar Maneuvering Targets Tracking(RMTT) in clutter is a quite challenging issue due to the errors in the models and the varying dynamics of the processes. Modern radar tracking system calls for the adaptive signal and data processing algorithm urgently to adapt the uncertainty of the environment. The mechanism of human cognition can help persons cope with the similar diffi-culties in visual tracking. Inspired by human cognition mechanism, a comprehensive method for RMTT is proposed. In the method, the model transition probability in Interacting Multiple Model(IMM) and the validation gate can be adjusted dynamically with target maneuver;the waveform in radar transmitter can vary with the perception of the environment. Experimental results in cluttered scenes show that the proposed algorithm is more accurate for perceiving the environment and targets, and the waveform selection algorithm is better than that with fixed waveform.展开更多
药物靶标作用关系预测是一种重要的辅助药物研发手段,而生物实验验证药物靶标作用关系耗钱耗时,因此,在数据库中查询验证预测的药物靶标作用关系是对预测方法的重要评价.基于KEGG,DrugBank,ChEMBL这3个数据库,利用爬虫获取信息的方式设...药物靶标作用关系预测是一种重要的辅助药物研发手段,而生物实验验证药物靶标作用关系耗钱耗时,因此,在数据库中查询验证预测的药物靶标作用关系是对预测方法的重要评价.基于KEGG,DrugBank,ChEMBL这3个数据库,利用爬虫获取信息的方式设计开发了药物靶标作用关系查询验证方法DTcheck(drug-target check),实现了对于提供KEGG DRUG ID及KEGG GENES ID的药物靶标对的高效查询验证功能,并利用DTcheck分别为Enzyme,IC(ion channel),GPCR(G-protein-coupled receptor),NR(nuclear receptor)四个标准数据集扩充新增药物靶标作用关系907,766,458,40对.此外,结合DTcheck查询验证,以BLM(bipartite local models)方法为例分析了预测结果的评价问题,结果表明,采用AUC(area under curve)值评价药物靶标作用关系预测方法没有Top N评价合理,且AUC值低的BLMd方法在预测新的药物靶标作用关系时优于AUC值高的BLMmax方法.展开更多
基金National Natural Science Foundation of China(Grant No.20852001)"985"Project Foundation(Grant No.985-2-126-121 )+1 种基金The Key Laboratory Grant(Grant No.20080104)National Basic Research Program of China(Grant No.973 Program,2010CB 12300)
文摘The ability to knockdown the expression of an endogenous gene by RNAi has emerged as a powerful strategy for the rapid identification of specific gene functions. Vector-based constitutive expression of shRNA can result in stable and efficient knockdown of target genes. However, constitutive expression of shRNA imposes major limitations when analyzing the fimction of genes whose expression is vital for the survival of an organism. Inducible RNAi systems can circumvent this limitation by enabling the inhibition of expression of an essential gene only when the inducing agent is present, and the level of knockdown of the essential gene can be controlled and adjusted by the concentration of inducing agent. In this review, we briefly summarize the recent development of various inducible RNAi systems and their potential applications in drug target validation.
基金Supported by the National Natural Science Foundation of China (30570990, 30471059, 31171578)the "863" project (2008AA10Z153)+2 种基金the Key Research Plan of Heilongjiang Province (GA06B103-3)the Innovation Research Group of NEAU (CXT004)the Research Fund for the Doctoral Program of Higher Education of China (20102325120002)
文摘MicroRNAs (miRNAs) are a group of regulatory RNAs that regulate gene expression post-transcriptionally by the degradation or translational inhibition of their target messenger RNAs (mRNAs). Regulation is accomplished when the 22-25 nucleotide miRNAs bind to complementary sequences in the 3'-untranslated regions (UTR). One barrier to miRNA research is to find target genes. Although computational target predictions have shed light on important aspects of microRNA target recognition, questions remain concerning the rates of false positives. In addition, we do not completely understand how microRNAs can recognize and regulate their targets. As such, experimental positive predictions and allow for an unbiased stu ap dy proaches are required, which can reflect in vivo processes, eliminating false of microRNA target recognition. In this review, we summarized experimental approaches that have been described for the identification and validation of mRNA targets associated with specific miRNAs.
基金co-supported by the National Natural Science Foundation of China(No.61671453)the Anhui Province Natural Science Fund Project,China(No.1608085MF123)
文摘Radar Maneuvering Targets Tracking(RMTT) in clutter is a quite challenging issue due to the errors in the models and the varying dynamics of the processes. Modern radar tracking system calls for the adaptive signal and data processing algorithm urgently to adapt the uncertainty of the environment. The mechanism of human cognition can help persons cope with the similar diffi-culties in visual tracking. Inspired by human cognition mechanism, a comprehensive method for RMTT is proposed. In the method, the model transition probability in Interacting Multiple Model(IMM) and the validation gate can be adjusted dynamically with target maneuver;the waveform in radar transmitter can vary with the perception of the environment. Experimental results in cluttered scenes show that the proposed algorithm is more accurate for perceiving the environment and targets, and the waveform selection algorithm is better than that with fixed waveform.
文摘药物靶标作用关系预测是一种重要的辅助药物研发手段,而生物实验验证药物靶标作用关系耗钱耗时,因此,在数据库中查询验证预测的药物靶标作用关系是对预测方法的重要评价.基于KEGG,DrugBank,ChEMBL这3个数据库,利用爬虫获取信息的方式设计开发了药物靶标作用关系查询验证方法DTcheck(drug-target check),实现了对于提供KEGG DRUG ID及KEGG GENES ID的药物靶标对的高效查询验证功能,并利用DTcheck分别为Enzyme,IC(ion channel),GPCR(G-protein-coupled receptor),NR(nuclear receptor)四个标准数据集扩充新增药物靶标作用关系907,766,458,40对.此外,结合DTcheck查询验证,以BLM(bipartite local models)方法为例分析了预测结果的评价问题,结果表明,采用AUC(area under curve)值评价药物靶标作用关系预测方法没有Top N评价合理,且AUC值低的BLMd方法在预测新的药物靶标作用关系时优于AUC值高的BLMmax方法.