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Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer.

Clarke K, Daubon T, Turan N, Soulet F, Mohd Zahari M, Ryan KR, Durant S, He S, Herbert J, Ankers J, Heath JK, Bjerkvig R, Bicknell R, Hotchin NA, Bikfalvi A, Falciani F - PLoS Genet. (2015)

Bottom Line: Glioblastoma patients have an average survival time of less than 15 months.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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Computational Biology and Modelling (CCBM), Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom; INSERM U1029, University Bordeaux, Pessac, France.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Overview of the analysis and validation strategy.
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pgen.1005325.g001: Overview of the analysis and validation strategy.

Mentions: Our study is based on a complex data analysis workflow which includes several complementary reverse engineering techniques to address the important challenge of generating and validating hypotheses outlining the main factors underlying the control and maintenance of glioma stage. The strategy we followed, which is summarised in Fig 1, is based on several cycles of data acquisition, computational analysis, hypothesis generation and experimental validation.


Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer.

Clarke K, Daubon T, Turan N, Soulet F, Mohd Zahari M, Ryan KR, Durant S, He S, Herbert J, Ankers J, Heath JK, Bjerkvig R, Bicknell R, Hotchin NA, Bikfalvi A, Falciani F - PLoS Genet. (2015)

Overview of the analysis and validation strategy.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488580&req=5

pgen.1005325.g001: Overview of the analysis and validation strategy.
Mentions: Our study is based on a complex data analysis workflow which includes several complementary reverse engineering techniques to address the important challenge of generating and validating hypotheses outlining the main factors underlying the control and maintenance of glioma stage. The strategy we followed, which is summarised in Fig 1, is based on several cycles of data acquisition, computational analysis, hypothesis generation and experimental validation.

Bottom Line: Glioblastoma patients have an average survival time of less than 15 months.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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Computational Biology and Modelling (CCBM), Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom; INSERM U1029, University Bordeaux, Pessac, France.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus