Examining tissue differentiation stability through large scale, multi-cellular pathway modeling

Genetic expression and control pathways can be successfully modeled as electrical circuits. To tackle large multicellular and genome scale simulations, the massively-parallel, electronic circuit simulator, Xyce™ [11], was adapted to address biological problems. Unique to this bio-circuit simulator is the ability to simulate not just one or a set of genetic circuits in a cell, but many cells and their internal circuits interacting through a common environment. Additionally, the circuit simulator Xyce can couple to the optimization and uncertainty analysis framework Dakota [2] allowing one to find viable parameter spaces for normal cell functionality and required parameter ranges for unknown or difficult to measure biological constants. Using such tools, we investigate the Drosophila sp. segmental differentiation network's stability as a function of initial conditions.