Exploring the topology of complex phylogenomic and transcriptomic networks

[摘要] ENGLISH ABSTRACT: This thesis involved the development and application of network approachesfor the construction, analysis and visualization of phylogenomic and transcriptomicnetworks.A co-evolutionary network model of grapevine genes was constructed basedon three mechanisms of evolution. The investigation of local neighbourhoodsof this network revealed groups of functionally related genes, illustrating thatthe multi-mechanism evolutionary model was identifying groups of potentiallyco-evolving genes.An extended network definition, namely 3-way networks, was investigated,in which edges model relationships between triplets of objects. Strategies forweighting and pruning these 3-way networks were developed and applied toa phylogenomic dataset of 211 bacterial genomes. These 3-way bacterial networkswere compared to standard 2-way network models constructed from thesame dataset. The 3-way networks modelled more complex relationships andrevealed relationships which were missed by the two-way network models.Network meta-modelling was explored in which global network and node-bynodenetwork comparison techniques were applied in order to investigate theeffect of the similarity metric chosen on the topology of multiple types ofnetworks, including transcriptomic and phylogenomic networks. Two new networkcomparison techniques were developed, namely PCA of Topology Profilesand Cross-Network Topological Overlap. PCA of Topology Profiles compares networks based on a selection of network topology indices, whereas Cross-Network Topological Overlap compares two networks on a node-by-node level,identifying nodes in two networks with similar neighbourhood topology andthus highlighting areas of the networks with conflicting topologies. These networkcomparison methods clearly indicated how the similarity metric chosento weight the edges of the network influences the resulting network topology,consequently influencing the biological interpretation of the networks.

[发布机构] Stellenbosch University