Glioblastoma (GBM) is a highly aggressive and treatment-resistant type of brain cancer. There is a pressing need to discover new treatment options. An understanding of the gene regulation circuits activated in clinically-relevant GBM samples promises to expose potential new therapeutic targets. Although notable progress has been achieved through genomics and pre-clinical in vivo applications, the complexity of this biological control circuitry in clinically-relevant data remains to be disentangled and exploited for translational research purposes. In this context, microRNAs (miRNAs) and non-long-coding RNAs (lncRNAs) have been shown as potentially new critical components of the glioma-specific transcriptional machinery.CIRCUITOMA aims to identify novel regulatory circuits involving transcription factors (TFs), miRNAs, lncRNAs and other genes in GBM. Using data generated at CRP-Santé together with public datasets, we will go beyond the identification of differentially expressed coding and non-coding genes into the specification of regulatory motifs implicated in GBM tumorigenesis and response to treatment. Specifically, the project will adapt and combine algorithms previously published by the partners at Vanderbilt University and CRP-Santé to detect and integrate TF-miRNA-gene and TF-lncRNA-gene association loops. A selection of the most statistically reliable and biologically interesting predictions will be unified to generate a global map of regulatory associations in GBM. We will search and describe candidate regulatory modules, which can harbour cross-regulatory mechanisms among the control loops. At the conclusion of this project, we will offer a compendium of control loops and modules activated in gliomas in response to treatment. CRP-Santé will afterwards be in the capacity to validate, in vitro or in vivo, the most biologically relevant predictions.A key innovation of this project is the identification and integration of TF-miRNA-gene and TF-lncRNA-gene association networks. Moreover, by joining complementary efforts and resources at the partner institutions, we will offer a systems-level characterization of post-transcriptional regulation that is currently lacking in glioma research. The resulting tools and predictions will enhance our competence in searching for novel treatment targets. In the longer term, this will offer opportunities for new translational research. At CRP-Santé, scientific excellence and the potential socio-economic impact of our activities will be considerably heightened through international, cross-disciplinary cooperation.