| Summary: | To comprehend the immense complexity that drives biological systems, it is necessary to generate hypotheses of system behaviour. This is because one can observe the results of a biological process and have knowledge of the molecular/genetic components, but not directly witness biochemical interaction mechanisms. Hypotheses can be tested in silico which is considerably cheaper and faster than “wet” lab trialand- error experimentation. Bio-systems are traditionally modelled using ordinary differential equations (ODEs). ODEs are generally suitable for the approximation of a (test tube sized) in vitro system trajectory, but cannot account for inherent system noise or discrete event behaviour. Most in vivo biochemical interactions occur within small spatially compartmentalised units commonly known as cells, which are prone to stochastic noise due to relatively low intracellular molecular populations. Stochastic simulation algorithms (SSAs) provide an exact mechanistic account of the temporal evolution of a bio-system, and can account for noise and discrete cellular transcription and signalling behaviour. Whilst this reaction-by-reaction account of system trajectory elucidates biological mechanisms more comprehensively than ODE execution, it comes at increased computational expense. Scaling to the demands of modern biology requires ever larger and more detailed models to be executed. Scientists evaluating and engineering tissue-scale and bacterial colony sized biosystems can be limited by the tractability of their computational hypothesis testing techniques. This thesis evaluates a hypothesised relationship between SSA computational performance and biochemical model characteristics. This relationship leads to the possibility of predicting the fastest SSA for an arbitrary model - a method that can provide computational headroom for more complex models to be executed. The research output of this thesis is realised as a software package for meta-stochastic simulation called ssapredict. Ssapredict uses statistical classification to predict SSA performance, and also provides high performance stochastic simulation implementations to the wider community.
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