Unravelling the complexity of metabolic networks

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Pearcy, N., 2015. Unravelling the complexity of metabolic networks. PhD, Nottingham Trent University.

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Abstract

Network science provides an invaluable set of tools and techniques for improving our understanding of many important biological processes at the systems level. A network description provides a simplied view of such a system, focusing upon the interactions between a usually large number of similar biological units. At the cellular level, these units are usually interacting genes, proteins or small molecules, resulting in various types of biological networks. Metabolic networks, in particular, play a fundamental role, since they provide the building blocks essential for cellular function, and thus, have recently received a lot of attention. In particular, recent studies have revealed a number of universal topological characteristics, such as a small average path-length, large clustering coecient and a hierarchical modular structure. Relations between structure, function and evolution, however, for even the simplest of organisms is far from understood. In this thesis, we employ network analysis in order to determine important links between an organism's metabolic network structure and the environment under which it evolved. We address this task from two dierent perspectives: (i) a network classication approach; and (ii) a more physiologically realistic modelling approach, namely hypernetwork models. One of the major contributions of this thesis is the development of a novel graph embedding approach, based on low-order network motifs, that compares the structural properties of large numbers of biological networks simultaneously. This method was prototyped on a cohort of 383 bacterial networks, and provides powerful evidence for the role that both environmental variability, and oxygen requirements, play in the forming of these important networked structures. In addition to this, we consider a hypernetwork formalism of metabolism, in an attempt to extend complex network reasoning to this more complicated, yet physiologically more realistic setting. In particular, we extend the concept of network reciprocity to hypernetworks, and again evidence a signicant relationship between bacterial hypernetwork structure and the environment in which these organisms evolved. Moreover, we extend the concept of network percolation to undirected hypernetworks, as a technique for quantifying robustness and fragility within metabolic hypernetworks, and in the process nd yet further evidence of increased topological complexity within organisms inhabiting more uncertain environments. Importantly, many of these relationships are not apparent when considering the standard approach, thus suggesting that a hypernetwork formalism has the potential to reveal biologically relevant information that is beyond the standard network approach.

Item Type:	Thesis
Creators:	Pearcy, N.
Date:	August 2015
Rights:	This work is the intellectual property of the author.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	29 Jun 2016 11:26
Last Modified:	29 Jun 2016 11:26
URI:	https://irep.ntu.ac.uk/id/eprint/28040