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Title: Bayesian inference for protein signalling networks
Author: Oates, Christopher J.
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2013
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Cellular response to a changing chemical environment is mediated by a complex system of interactions involving molecules such as genes, proteins and metabolites. In particular, genetic and epigenetic variation ensure that cellular response is often highly specific to individual cell types, or to different patients in the clinical setting. Conceptually, cellular systems may be characterised as networks of interacting components together with biochemical parameters specifying rates of reaction. Taken together, the network and parameters form a predictive model of cellular dynamics which may be used to simulate the effect of hypothetical drug regimens. In practice, however, both network topology and reaction rates remain partially or entirely unknown, depending on individual genetic variation and environmental conditions. Prediction under parameter uncertainty is a classical statistical problem. Yet, doubly uncertain prediction, where both parameters and the underlying network topology are unknown, leads to highly non-trivial probability distributions which currently require gross simplifying assumptions to analyse. Recent advances in molecular assay technology now permit high-throughput data-driven studies of cellular dynamics. This thesis sought to develop novel statistical methods in this context, focussing primarily on the problems of (i) elucidating biochemical network topology from assay data and (ii) prediction of dynamical response to therapy when both network and parameters are uncertain.
Supervisor: Not available Sponsor: Engineering and Physical Sciences Research Council (EPSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QA Mathematics ; QP Physiology