Background:The bone is the most frequent target of metastatic breast ***, the underlying molecular mechanisms are *** many microarray studies have reported gene signatures that can predict metastasis in breast cancer,...
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Background:The bone is the most frequent target of metastatic breast ***, the underlying molecular mechanisms are *** many microarray studies have reported gene signatures that can predict metastasis in breast cancer,predicting cancer metastasis to a specific organ,such as to bone,remains a challenge in cancer study. Methods:Previously we proposed a concept CoMi(Context Specific miRNA activity), which could quantify the regulation activity of miRNA on specific context(CoMi activity) by calculating the statistical difference of the expression level between the miRNA targets and non-targets in a given context(GO term biological process),and demonstrated its application on predicting *** we extend this concept to CoMi module and use it to predict whether the cancer will metastasize to ***,CoMi features which are significant associated with the bone metastasis are identified by Cox proportional hazards regression. Based on the significant CoMi features,miRNAs regulate on the same context are regarded as a significant miRNA regulation *** each significant CoMi module is used to predict bone metastasis of breast cancer patients by sum up all the risk scores(Cox proportional hazards regression) of CoMi features in the module. Results:We tested the proposed method on a breast cancer cohort contain 855 samples' gene expression profiles together with bone metastasis *** bone metastasis specific CoMi modules are identified,such as module 'hemopoiesis',which has a log rank p value of 9.05e-07 in train dataset,0.0075 in test dataset and 0.0031 in independent test dataset. Considering the hematopoietic stem cell niche is a potential therapeutic target for bone metastatic tumors,our results might facilitate to identify the miRNAs regulation modules involved in hematopoietic stem cell niche. Conclusions:We proposed the concept of CoMi activity module,and identified some CoMi activity modules which could predict bone metas
A core task of drug discovery study is to identify the dependency between the genetic/ molecular makeups of the human body and disease *** we proposed a novel method for systematically screening the microRNAs regulati...
A core task of drug discovery study is to identify the dependency between the genetic/ molecular makeups of the human body and disease *** we proposed a novel method for systematically screening the microRNAs regulating cancer prognosis via driving a specific ppi (protein-protein interaction) *** this method, we integrated information from microRNAs expression, mRNAs expression and patient outcome, and tried to mine the in vivo dependency between microRNAs and ppi *** conditional dependency of the mRNAs expression (G), microRNAs expression (M) and phenotype (P) was calculated, and the permutation was conduct to screen the significant Conditional Mutual Information Ⅰ (G, P|M).In this study we test the proposed method on autophagy protein networks in ovarian cancer as *** is a cellular process involved the degradation of cell's own components, in which cytoplasmic contents are sequestered into a double-membrane called autophagosome and then subsequently delivered to lysosome for *** identified a group of microRNAs, which could regulate the hub nodes of autophagy ppi *** experimentally demonstrated that the transfection of the mimics of these microRNAs could inhibit autophagy via inhibiting the target gene: ***, the miRNA-target gene pair is significantly associated with prognosis in a cohort of ovarian cancer patients .
A core task of drug discovery study is to identify the dependency between the genetic/ molecular makeups of the human body and disease *** we proposed a novel method for systematically screening the microRNAs regulati...
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A core task of drug discovery study is to identify the dependency between the genetic/ molecular makeups of the human body and disease *** we proposed a novel method for systematically screening the microRNAs regulating cancer prognosis via driving a specific ppi(protein-protein interaction) *** this method,we integrated information from microRNAs expression,mRNAs expression and patient outcome,and tried to mine the in vivo dependency between microRNAs and ppi *** conditional dependency of the mRNAs expression(G),microRNAs expression(M) and phenotype(P) was calculated, and the permutation was conduct to screen the significant Conditional Mutual Information I (G,P|M).In this study we test the proposed method on autophagy protein networks in ovarian cancer as *** is a cellular process involved the degradation of cell's own components,in which cytoplasmic contents are sequestered into a double-membrane called autophagosome and then subsequently delivered to lysosome for *** identified a group of microRNAs,which could regulate the hub nodes of autophagy ppi *** experimentally demonstrated that the transfection of the mimics of these microRNAs could inhibit autophagy via inhibiting the target gene:***,the miRNA-target gene pair is significantly associated with prognosis in a cohort of ovarian cancer patients.
Background: Much effort has been expended in exploring the connections between transcriptome, disease and drug, based on the premise that drug induced perturbations in the transcriptome will affect the phenotype and f...
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Background: Much effort has been expended in exploring the connections between transcriptome, disease and drug, based on the premise that drug induced perturbations in the transcriptome will affect the phenotype and finally help to cure a disease. MicroRNAs (miRNAs) play a key role in the regulation of the transcriptome and have been identified as a key mediator in human disease and drug response. However, even if miRNA expression can be precisely detected, the information regarding miRNAs action on a particular part of the transcriptome is still lacking. Here, we introduced a novel concept, the Context-specific MiRNA activity (CoMi activity), to reflect a miRNA's regulation effect on a context specific gene set, by calculating the statistical difference between the distributions of its target gene expression and non-target gene expression. In this study we investigate whether CoMi activity could provide a novel perspective on miRNA mechanisms of action in disease and drug response, and facilitate in silico drug screening. Results: Using breast cancer as an example, we examined the CoMi activity based on a Gene Ontology (GO) term as context. Then we constructed a differential CoMi activity network (cancer vs. normal), based on the comi activity represents as a link between miRNAs and GO terms, (e.g. hsa-miR-27a's regulation on GO term "apoptosis"). The topological analysis of the generated network demonstrated that the cancer specific CoMi network is a scale free network. The highly connected nodes highlighted a group of known onco-miRNAs (e.g. hsa miR-183*) and tumor suppressor miRNAs (e.g. hsa-miR-34a), as well as some well-known cancer related GO biological processes (e.g. apoptosis). Interestingly, we found that chemotherapeutic drug treatment can counteract the dis regulated CoMi activity in the cancer-specific network. For instance, 100% of down-regulated CoMi activities in a "core" breast cancer network contains apoptosis-related GO terms that could be counte
MicroRNAs can regulate hundreds of target genes and play a pivotal role in a broad range of biological process. However, relatively little is known about how these highly connected miRNAs-target networks are remodelle...
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MicroRNAs can regulate hundreds of target genes and play a pivotal role in a broad range of biological process. However, relatively little is known about how these highly connected miRNAs-target networks are remodelled in the context of various diseases. Here we examine the dynamic alteration of context-specific miRNA regulation to determine whether modified microRNAs regulation on specific biological processes is a useful information source for predicting cancer prognosis. A new concept, Context-specific miRNA activity (CoMi activity) is introduced to describe the statistical difference between the expression level of a miRNA's target genes and non-targets genes within a given gene set (context).
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