Integrative network modelling of the dasatinib treatment in glioblastoma stem cells

Senger, Gökçe
Glioblastoma (GBM), the most aggressive type of the glial tumours, is thought to be widely promoted by stem-like cells. Although certain cancer types have been radically treated with Receptor Tyrosine Kinases (RTKs) inhibitors, prior studies demonstrate that treatment Glioblastoma Stem Cells (GSCs) with RTK inhibitors led to dynamic interconversion from proliferative to slow-cycling, persistent state. In this work, we use the publicly available RNA-Seq and ChIP-Seq data in naive patient-derived GBM cell line (GSC8), 12-day and chronic dasatinib treated GSC8 published by Liau et al (Liau et al., 2017) and apply an integrative approach to develop a further explanation for reversible transition of GSCs and to model the effect of the dasatinib treatment in a network context. We first used the Garnet module in Omics Integrator software which identifies transcription factor binding sites from epigenomic data, relates known and predicted transcription factor binding sites to gene expression and finds the significantly active transcription factors. Then, we used the Forest module of the Omics Integrator software to reconstruct an optimal network for each condition by integrating significantly active transcription factors and a confidence weighted protein interactome. As a result, we obtained three condition specific networks and clustered them based on the topology of these networks. Each module was analysed in terms of pathway enrichments. Then, we compared these networks based on the node, edge and pathway similarities. We reveal that GSCs tend to activate RTK-targeted genes and upregulate neurodevelopmental programs by reorganizing chromatin modifications.


3D spatial organization and network-guided comparison of mutation profiles in glioblastoma
Dinçer, Cansu; Tunçbağ, Nurcan; Department of Bioinformatics (2019)
Glioblastoma multiforme (GBM) is the most aggressive and heterogeneous type of brain tumor. The heterogeneity of GBM is the main obstacle to develop effective treatment strategies. In this study, we aimed to decrease the heterogeneity among GBM patients from The Cancer Genome Atlas (TCGA), classify the patients and propose therapeutic hypothesis for patient groups by using patient mutation profiles. We therefore implemented a systems level approach to mutations using their biophysical characteristics and or...
The genomic and epigenomic evolutionary history of papillary renal cell carcinomas
Zhu, Bin; et. al. (2020-06-01)
Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of sp...
Liposomes as immunological adjuvants and vaccine carriers
Gregoriadis, G; Gursel, I; Gürsel, Mayda; McCormack, B (1996-08-01)
Work by numerous laboratories in the last two decades has shown that liposomes promote humoral and cell-mediated immunity to a large variety of bacterial, protozoan, viral and tumour cell antigens. This immunoadjuvant action of liposomes depends on their structural characteristics which control vesicle fate in vivo including the mode of antigen interaction with antigen-presenting cells. Liposomal adjuvanticity is further promoted by receptor mediated targeting to macrophages or the presence of co-adjuvants ...
Leveraging the Molecular Signatures of Cancer for Dynamic Network Modeling
Tunçbağ , Nurcan; Ayar , Enes Sefa (Orta Doğu Teknik Üniversitesi Enformatik Enstitüsü; 2022-10)
Molecular heterogeneity and resistance to the treatment are among the obstacles in developing treatment strategies in cancer. Therefore, transforming patient-specific molecular data into clinically interpretable knowledge is fundamental in personalized medicine. However, not all molecular alterations drive cancer. The distinction of drivers from latent drivers and passengers, their cooperativity and exclusivity, and the temporal order of accumulation of molecular alterations is a crucial yet daunting, unsol...
Evaluation of methylation profiles of an epidermal growth factor receptor gene in a head and neck squamous cell carcinoma patient group
Mutlu, M.; Mutlu, Pelin; Azarkan, S.; Baylr, Ö.; Öcal, B.; Saylam, G.; KORKMAZ, MEHMET HAKAN (2021-03-23)
Upregulation of the epidermal growth factor receptor (EGFR) gene has shown an important impact on the development of head and neck cancers due to its important regulation role on multiple cell signaling pathways. The aim of this study was to investigate the methylation pattern of the promoter region of the EGFR gene between head and neck squamous cell carcinoma (HNSCC) patients and a control group. Forty-seven unrelated HNSCC patients, clinically diagnosed at the Department of Otorhinolaryngology, Dlşkapl Y...
Citation Formats
G. Senger, “Integrative network modelling of the dasatinib treatment in glioblastoma stem cells,” M.S. - Master of Science, Middle East Technical University, 2019.