Mathematical modelling is playing an increasingly important role in helping us to understand biological systems. The construction of biological models typically requires the use of experimentally-measured parameter values. However, varying degrees of uncertainty surround virtually all parameters in these models. Sensitivity analysis is one of the most important tools for the analysis of models, and shows how the outputs of a model, such as concentrations and reaction fluxes, are dependent on the parameters which make up the input. Unfortunately, small changes in parameter values can lead to the results of a sensitivity analysis changing significantly. The results of such analyses must therefore be interpreted with caution, particularly if a high degree of uncertainty surrounds the parameter values. Global sensitivity analysis methods can help in such situations by allowing sensitivities to be calculated over a range of possible parameter values. However, these techniques are computationally expensive, particularly for larger, more detailed models. Software was developed to enable a number of computationally-intensive modelling tasks, including two global sensitivity analysis methods, to be run in parallel in a high-throughput computing environment. The use of high-throughput computing enabled the run time of these analyses to be drastically reduced, allowing models to be analysed to a degree that would otherwise be impractical or impossible. Global sensitivity analysis using high-throughput computing was performed on a selection of both theoretical and physiologically-based models. Varying degrees of parameter uncertainty were considered. These analyses revealed instances in which the results of a sensitivity analysis were valid, even under large degrees of parameter variation. Other cases were found for which only a slight change in parameter values could completely change the results of the analysis. Parameter uncertainties are a real problem in biological systems modelling. This work shows how, with the help of high-throughput computing, global sensitivity analysis can become a practical part of the modelling process.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:570277 |
| Date | January 2013 |
| Creators | Kent, Edward Lander |
| Contributors | Westerhoff, Hans; Pedrosa Mendes, Pedro |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.research.manchester.ac.uk/portal/en/theses/sensitivity-analysis-of-biochemical-systems-using-highthroughput-computing(80eb7aa9-d316-4a72-a6c2-731c6052ea84).html |
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