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A local genetic algorithm for the identification of condition-specific microRNA-gene modules.

ABSTRACT: Transcription factor and microRNA are two types of key regulators of gene expression. Their regulatory mechanisms are highly complex. In this study, we propose a computational method to predict condition-specific regulatory modules that consist of microRNAs, transcription factors, and their commonly regulated genes. We used matched global expression profiles of mRNAs and microRNAs together with the predicted targets of transcription factors and microRNAs to construct an underlying regulatory network. Our method searches for highly scored modules from the network based on a two-step heuristic method that combines genetic and local search algorithms. Using two matched expression datasets, we demonstrate that our method can identify highly scored modules with statistical significance and biological relevance. The identified regulatory modules may provide useful insights on the mechanisms of transcription factors and microRNAs.

SUBMITTER: Mu W

PROVIDER: S-EPMC3564382 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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A local genetic algorithm for the identification of condition-specific microRNA-gene modules.

Mu Wenbo W Roqueiro Damian D Dai Yang Y

TheScientificWorldJournal 20130121

Transcription factor and microRNA are two types of key regulators of gene expression. Their regulatory mechanisms are highly complex. In this study, we propose a computational method to predict condition-specific regulatory modules that consist of microRNAs, transcription factors, and their commonly regulated genes. We used matched global expression profiles of mRNAs and microRNAs together with the predicted targets of transcription factors and microRNAs to construct an underlying regulatory net ...[more]

PMID: 23401666

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Project description:BackgroundGenome-wide association studies have identified genetic variants associated with the risk of brain-related diseases, such as neurological and psychiatric disorders, while the causal variants and the specific vulnerable cell types are often needed to be studied. Many disease-associated genes are expressed in multiple cell types of human brains, while the pathologic variants affect primarily specific cell types. We hypothesize a model in which what determines the manifestation of a disease in a cell type is the presence of disease module comprised of disease-associated genes, instead of individual genes. Therefore, it is essential to identify the presence/absence of disease gene modules in cells.MethodsTo characterize the cell type-specificity of brain-related diseases, we construct human brain cell type-specific gene interaction networks integrating human brain nucleus gene expression data with a referenced tissue-specific gene interaction network. Then from the cell type-specific gene interaction networks, we identify significant cell type-specific disease gene modules by performing statistical tests.ResultsBetween neurons and glia cells, the constructed cell type-specific gene networks and their gene functions are distinct. Then we identify cell type-specific disease gene modules associated with autism spectrum disorder and find that different gene modules are formed and distinct gene functions may be dysregulated in different cells. We also study the similarity and dissimilarity in cell type-specific disease gene modules among autism spectrum disorder, schizophrenia and bipolar disorder. The functions of neurons-specific disease gene modules are associated with synapse for all three diseases, while those in glia cells are different. To facilitate the use of our method, we develop an R package, CtsDGM, for the identification of cell type-specific disease gene modules.ConclusionsThe results support our hypothesis that a disease manifests itself in a cell type through forming a statistically significant disease gene module. The identification of cell type-specific disease gene modules can promote the development of more targeted biomarkers and treatments for the disease. Our method can be applied for depicting the cell type heterogeneity of a given disease, and also for studying the similarity and dissimilarity between different disorders, providing new insights into the molecular mechanisms underlying the pathogenesis and progression of diseases.

Dataset Information

A local genetic algorithm for the identification of condition-specific microRNA-gene modules.

Publications

A local genetic algorithm for the identification of condition-specific microRNA-gene modules.

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