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Pathological cardiac hypertrophy (CH) is associated with increased heart failure risk and sudden cardiac death. Several transcription factors (TFs) and miRNAs were implicated in CH, and their high combinatorial action in gene expression regulation is becoming more clear. We adopted a systems biology approach to construct a comprehensive TF-miRNA co-regulatory network in CH and systematically characterize its structure, from node- to systems-level properties. Parallel expression profiles for miRNAs and messenger RNA (mRNA) from an in vitro model of CH were integrated with experimentally validated interactions from seven curated databases to build the CH-related TF-miRNA regulatory network. To leverage this network, we proposed a completely unsupervised approach to identify core regulatory elements, based on Borda count aggregation of distinct network-based properties. By combining node …