On Boolean Modeling of Gene Regulatory Networks for Improved Cancer Combinatorial Therapy Design and Transcriptome Assemblies for Pacific Whiteleg Shrimp
Abstract
Cancer cells are known to exhibit atypical metabolic characteristics. While alterations in tumor cell metabolism are necessary for the sustained uncontrolled cell growth that characterizes cancer, it is also a vulnerability which can be exploited to design therapies that preferentially target cancer cells. We develop a testable theoretical framework for cancer therapy design which is used to elucidate a role for the metabolism targeting anti-diabetic drug Metformin as part of a combination cocktail therapy that could potentially provide better and less toxic clinical outcomes.
Castration-resistant prostate cancer is an advanced form of prostate cancer with limited treatment options where patients become refractory to surgical or medical castration. We use Boolean logic modeling of the key signaling pathways implicated in the development and progression of this malignancy to simultaneously test various combinations of agents for their ecacy in attenuating cancer growth and design targeted therapies for the management of the disease. Furthermore, stochastic computational modeling is utilized to identify potentially vulnerable components in the network that may serve as viable candidates for drug development.
Finally, we present novel transcriptome assemblies and functional annotations for Pacific whiteleg shrimp, a non-model organism of significant economic import that lacks solid transcriptome and genome references. In addition, as evaluating the quality of de novo transcriptome assemblies has proven to be challenging, we propose a pipeline comprising multiple quality check metrics that in unison provide a clear evaluation of assembly performance.
Subject
cancercombination therapy design
Boolean modeling
gene regulatory networks
transcriptome assemblies
Pacific whiteleg shrimp
Citation
Arshad, Osama Ali (2017). On Boolean Modeling of Gene Regulatory Networks for Improved Cancer Combinatorial Therapy Design and Transcriptome Assemblies for Pacific Whiteleg Shrimp. Doctoral dissertation, Texas A & M University. Available electronically from https : / /hdl .handle .net /1969 .1 /161335.