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Title: Metabolic profiling of plant disease : from data alignment to pathway predictions
Author: Perera, Munasinhage Venura Lakshitha
ISNI:       0000 0004 2736 4605
Awarding Body: University of Exeter
Current Institution: University of Exeter
Date of Award: 2011
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Understanding the complex metabolic networks present in organisms, through the use of high throughput liquid chromatography coupled mass spectrometry, will give insight into the physiological changes responding to stress. However the lack of a proper work flow and robust methodology hinders verifiable biological interpretation of mass profiling data. In this study a novel workflow has been developed. A novel Kernel based feature alignment algorithm, which outperformed Agilent’s Mass profiler and showed roughly a 20% increase in alignment accuracy, is presented for the alignment of mass profiling data. Prior to statistical analysis post processing of data is carried out in two stages, noise filtering is applied to consensus features which were aligned at a 50% or higher rate. Followed by missing value imputation a method was developed that outperforms both at model recovery and false positive detection. The use of parametric methods for statistical analysis is inefficient and produces a large number of false positives. In order to tackle this three non-parametric methods were considered. The histogram method for statistical analysis was found to yield the lowest false positive rate. Data is presented which was analysed using these methods to reveal metabolomic changes during plant pathogenesis. A high resolution time series dataset was produced to explore the infection of Arabidopsis thaliana by the (hemi) biotroph Pseudomonas syringe pv tomato DC3000 and its disarmed mutant DC3000hrpA, which is incapable of causing infection. Approximately 2000 features were found to be significant through the time series. It was also found that by 4h the plants basal defence mechanism caused the significant ‘up-regulation’ of roughly 400 features, of which 240 were found to be at a 4-fold change. The identification of these features role in pathogenesis is supported by the fact that of those features found to discriminate between treatments a number of pathways were identified which have previously been documented to be active due to pathogenesis
Supervisor: Yang, Ron ; Grant, Murray Sponsor: EPSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Untargeted metabolomics ; Mass profiling ; Plant pathogen interaction ; Liquid chromatography-mass spectrometry (LC-MS) ; Feature alignment ; Statistical analysis