Inference of low and high-grade glioma gene regulatory networks delineates the role of Rnd3 in establishing multiple hallmarks of cancer

Research output: Contribution to journalArticlepeer-review


  • Kim Clarke
  • Nil Turan Jurdzinski
  • Maihafizah Mohd Zahari
  • Katie Ryan
  • Sarah Durant
  • Thomas Daubon
  • Fabienne Soulet
  • John Herbert
  • John Ankers
  • Rolf Bjerkvig
  • Andreas Bikfalvi

External organisations

  • University of Liverpool
  • University of Bordeaux
  • University of Bergen


Gliomas are a highly heterogeneous group of brain tumours that are refractory to treatment, highly invasive and pro-angiogenic. Glioblastoma patients have an average survival time of less than 15 months. Understanding the molecular basis of different grades of glioma, from well differentiated, low-grade tumours to high-grade tumours, is a key step in defining new therapeutic targets. Here we use a data-driven approach to learn the structure of gene regulatory networks from observational data and use the resulting models to formulate hypothesis on the molecular determinants of glioma stage. Remarkably, integration of available knowledge with functional genomics datasets representing clinical and pre-clinical studies reveals important properties within the regulatory circuits controlling low and high-grade glioma. Our analyses first show that low and high-grade gliomas are characterised by a switch in activity of two subsets of Rho GTPases. The first one is involved in maintaining normal glial cell function, while the second is linked to the establishment of multiple hallmarks of cancer. Next, the development and application of a novel data integration methodology reveals novel functions of RND3 in controlling glioma cell migration, invasion, proliferation, angiogenesis and clinical outcome.


Original languageEnglish
Article numbere1005325
JournalPLoS Genetics
Issue number7
Publication statusPublished - 1 Jul 2015