Integrative network analysis is powerful in helping understand the underlying mechanisms of genetic and epigenetic perturbations for disease studies. Although it becomes clear that microRNAs, one type of epigenetic fa...Integrative network analysis is powerful in helping understand the underlying mechanisms of genetic and epigenetic perturbations for disease studies. Although it becomes clear that microRNAs, one type of epigenetic factors, have direct effect on target genes, it is unclear how microRNAs perturb downstream genetic neighborhood. Hence, we propose a network community approach to integrate microRNA and gene expression profiles, to construct an integrative genetic network perturbed by microRNAs. We apply this approach to an ovarian cancer dataset from The Cancer Genome Atlas project to identify the fluctuation of microRNA expression and its effects on gene expression. First, we perform expression quantitative loci analysis between microRNA and gene expression profiles via both a classical regression framework and a sparse learning model. Then, we apply the spin glass community detection algorithm to find genetic neighborhoods of the microRNAs and their associated genes. Finally, we construct an integrated network between microRNA and gene expression based on their community structure. Various disease related microRNAs and genes, particularly related to ovarian cancer, are identified in this network. Such an integrative network allows us to investigate the genetic neighborhood affected by microRNA expression that may lead to disease manifestation and progression.展开更多
基金supported in part by a Faculty Research Grant from the University of North Carolina at Charlotte to XS
文摘Integrative network analysis is powerful in helping understand the underlying mechanisms of genetic and epigenetic perturbations for disease studies. Although it becomes clear that microRNAs, one type of epigenetic factors, have direct effect on target genes, it is unclear how microRNAs perturb downstream genetic neighborhood. Hence, we propose a network community approach to integrate microRNA and gene expression profiles, to construct an integrative genetic network perturbed by microRNAs. We apply this approach to an ovarian cancer dataset from The Cancer Genome Atlas project to identify the fluctuation of microRNA expression and its effects on gene expression. First, we perform expression quantitative loci analysis between microRNA and gene expression profiles via both a classical regression framework and a sparse learning model. Then, we apply the spin glass community detection algorithm to find genetic neighborhoods of the microRNAs and their associated genes. Finally, we construct an integrated network between microRNA and gene expression based on their community structure. Various disease related microRNAs and genes, particularly related to ovarian cancer, are identified in this network. Such an integrative network allows us to investigate the genetic neighborhood affected by microRNA expression that may lead to disease manifestation and progression.
