Phylogenetic analysis black box

Date

2008-09

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Cranfield University

Department

Cranfield Health

Type

Thesis or dissertation

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Abstract


Molecular phylogenetics tries to resolve sequence evolution in order to provide the evolutionary relationship of homologous sequences: DNA, RNA or proteins. Phylogenetics acts at the beginning of the drug discovery process and is of great relevance in gene target selection, protein functionality inference and animal model selection. There are different methodologies to develop a phylogenetic analysis. However, none of them are 100% accurate. Therefore, it is not correct to rely on only one phylogenetic methodology to arrive at significant conclusions. The ideal use of phylogenetics is to perform a “robust” phylogenetic analysis that would involve the use of various methodologies and a comparison among their results. As most bioinformaticians performing phylogenetic analysis have expert knowledge in phylogenetics, this project intends to be a phylogenetic guide. Firstly, it provides a detailed introduction of phylogenetics giving a description of the most relevant methodologies. Secondly, a phylogenetic analysis of the superfamily ABC transporters was performed to provide an example of how to perform robust manual phylogenetics analysis and interpret these results. Furthermore, because of the relevance in pharmacology of the ABC transporters, discussion of the results here provided can be used to help the understanding of their ABC transporters evolution and implications in disease. Finally, the Phylogenetic analysis Black Box tool (PBB) has been generated. The program is a pipeline of the most relevant phylogenetic methods and provides easy and fast access to the non- phylogenetic expert user, allowing them to perform a robust phylogenetic analysis, in a time saving way and helping them in the results interpretation.

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Github

Keywords

Molecular phylogenetics, homologous sequences, DNA, RNA, PBB, drug discovery process

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