02000nas a2200157   4500008004100000022001400041245010400055210006900159260000900228300000900237490000600246520142200252100002201674700002101696856012501717       2019                        eng d  a2045-232200aExploring notch pathway to elucidate phenotypic plasticity and intra-tumor heterogeneity in gliomas0 aExploring notch pathway to elucidate phenotypic plasticity and i  cJUL   a94880 v93 a<p>The phenotypic plasticity and self-renewal of adult neural (aNSCs) and glioblastoma stem cells (GSCs) are both known to be governed by active Notch pathway. During development, GSCs can establish differential hierarchy to produce heterogeneous groups of tumor cells belong to different grades, which makes the tumor ecosystem more complex. However, the molecular events regulating these entire processes are unknown hitherto. In this work, based on the mechanistic regulations of Notch pathway activities, a novel computational framework is introduced to inspect the intra-cellular reactions behind the development of normal and tumorigenic cells from aNSCs and GSCs, respectively. The developmental dynamics of aNSCs/GSCs are successfully simulated and molecular activities regulating the phenotypic plasticity and self-renewal processes in normal and tumor cells are identified. A novel scoring parameter ``Activity Ratio'' score is introduced to find out driver molecules responsible for the phenotypic plasticity and development of different grades of tumor. A new quantitative method is also developed to predict the future risk of Glioblastoma tumor of an individual with appropriate grade by using the transcriptomics profile of that individual as input. Also, a novel technique is introduced to screen and rank the potential drug-targets for suppressing the growth and differentiation of tumor cells.</p>
1 aChowdhury, Saikat1 aSarkar, Ram, Rup  uhttps://library.ncl.res.in/content/exploring-notch-pathway-elucidate-phenotypic-plasticity-and-intra-tumor-heterogeneity