TABASCO: A single molecule, base-pair resolved gene expression simulator

Abstract

Background: Experimental studies of gene expression have identified some of the individual molecular components and elementary reactions that comprise and control cellular behavior. Given our current understanding of gene expression, and the goals of biotechnology research, both scientists and engineers would benefit from detailed simulators that can explicitly compute genome-wide expression levels as a function of individual molecular events, including the activities and interactions of molecules on DNA at single base pair resolution. However, for practical reasons including computational tractability, available simulators have not been able to represent genome-scale models of gene expression at this level of detail.

Evolutionarily Stable Attenuation by Genome Rearrangement in a Virus

“…, whether adaptive evolution reverses the attenuation, and on our ability to predict the evolutionary response to the reorganization. For prediction, we have a wealth of biochemical understanding of this phage (Dunn and Studier 1983; Molineux 2006) as well as a virtual model of the infection cycle (Endy et al 2000; Kosuri et al 2007). Each study uses a different modified T7 genome, selects it for fast growth, and monitors fitness and sequence evolution.…”

“…The T7 virtual model of the intracellular life cycle is a kinetic model that incorporates parameters for more than 100 genetic elements (Endy et al 2000; Kosuri et al 2007). It is versatile, allowing the programmer to specify an arbitrary linear order of those elements during genome entry, with consequent effects on the timing of the function of those elements.…”

“…After decades of genetic and biochemical work on T7 (Dunn and Studier 1983; Molineux 2006) an empirically parameterized virtual model of its infection cycle was developed (Endy et al 2000; Kosuri et al 2007), and various types of engineered genomes have been tested (Endy et al 2000; Bull and Molineux 2008); a cell-free system for growing T7 in vitro promises even further advances (Shin et al 2012). The combined approaches have been integrated with the hope of predicting not only the consequences of engineering but also of predicting evolution in response to engineering.…”

Mathematical modeling and synthetic biology

“…In addition time course dynamics may also require additional features such as explicitly modeling mRNA production and degradation [18]. As measuring techniques improve, models will necessarily need to become more complex to match the experimental results [28].…”

Synthetic Biology & Bioinformatics Prospects in the Cancer Arena

“…It provides connections to both parts databases and simulation environments, but it considers only one kind of signal carrier (RNA polymerases). It can invoke the simulator TABASCO (Kosuri et al, 2007), thus enabling genome scale simulations at single base-pair resolution. CellDesigner (Funahashi et al, 2003) has similar capabilities for graphical circuit composition.…”