Identifying MicroRNA and Gene Expression Networks Using Graph Communities

Integrative network analysis is powerful in helping understand the underlying mechanisms of genetic and epigenetic perturbations for disease studies.Although it becomes clear that micro RNAs,one type of epigenetic factors,have direct effect on target genes,it is unclear how micro RNAs perturb downstream genetic neighborhood.Hence,we propose a network community approach to integrate micro RNA and gene expression profiles,to construct an integrative genetic network perturbed by micro RNAs.We apply this approach to an ovarian cancer dataset from The Cancer Genome Atlas project to identify the fluctuation of micro RNA expression and its effects on gene expression.First,we perform expression quantitative loci analysis between micro RNA 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 micro RNAs and their associated genes.Finally,we construct an integrated network between micro RNA and gene expression based on their community structure.Various disease related micro RNAs 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 micro RNA expression that may lead to disease manifestation and progression.