Characterisation of xenometabolome signatures in complex biomatrices for enhanced human population phenotyping

Metabolic phenotyping facilitates the analysis of low molecular weight compounds in complex biological samples, with resulting metabolite profiles providing a window on endogenous processes and xenobiotic exposures. Accurate characterisation of the xenobiotic component of the metabolome (the xenometabolome) is particularly valuable when metabolic phenotyping is used for epidemiological and clinical population studies where exposure of participants to xenobiotics is unknown or difficult to control/estimate. Additionally, as metabolic phenotyping has increasingly been incorporated into toxicology and drug metabolism research, phenotyping datasets may be exploited to study xenobiotic metabolism at the population level. This thesis describes novel analytical and data-driven strategies for broadening xenometabolome coverage to allow effective partitioning of endogenous and xenobiotic metabolome signatures. The data driven strategy was multi-faceted, involving the generation of a reference database and the application of statistical methodologies. The database contains over 100 common xenobiotics profiles - generated using established liquid chromatography-mass-spectrometry methods – and provided the basis for an empirically derived screen for human urine and blood samples. The prevalence of these xenobiotics was explored in an exemplar phenotyping dataset (ALZ; n = 650; urine), with 31 xenobiotics detected in an initial screen. Statistical based methods were tailored to extract xenobiotic-related signatures and evaluated using drugs with well-characterised human metabolism. To complement the data-driven strategies for xenometabolome coverage, a more analytical based strategy was additionally developed. A dispersive solid phase extraction sample preparation protocol for blood products was optimised, permitting efficient removal of lipids and proteins, with minimal effect on low molecular weight metabolites. The suitability and reproducibility of this method was evaluated in two independent blood sample sets (AZstudy12; n=171, MARS; n=285). Finally, these analytical and statistical strategies were applied to two existing large-scale phenotyping study datasets: AIRWAVE (n = 3000 urine, n=3000 plasma samples) and ALZ (n= 650 urine, n= 449 serum) and used to explore both xenobiotic and endogenous responses to triclosan and polyethylene glycol exposure. Exposure to triclosan highlighted affected pathways relating to sulfation, whilst exposure to PEG highlighted a possible perturbation in the glutathione cycle. The analytical and statistical strategies described in this thesis allow for a more comprehensive xenometabolome characterisation and have been used to uncover previously unreported relationships between xenobiotic and endogenous metabolism.Open Acces

Evolutionary genomics : statistical and computational methods

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

Fruit Metabolism and Metabolomics

Over the past ten years, metabolomics strategies have allowed the relative or absolute quantitation of metabolite levels for the study of various biological questions in plant sciences. For fruit studies, in particular, they have participated in the identification of the genes underpinning fruit development and ripening. This book proposes examples of the current use of metabolomics studies of fruit for basic research or practical applications. It includes articles about several tropical and temperate fruit species. The studies concern fruit biochemical phenotyping, fruit metabolism during development and after harvest, including primary and specialized metabolisms, or bioactive compounds involved in fruit growth and environmental responses. The analytical strategies used are based mostly on liquid or gas chromatography coupled with mass spectrometry, but also on nuclear magnetic resonance and near-infrared spectroscopy. The effect of genotype, stages of development, or fruit tissue type on metabolomic profiles and corresponding metabolism regulations are addressed for fruit metabolism studies. The interest in combining other omics with metabolomics is also exemplified

Evolutionary Genomics

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

STK /WST 795 Research Reports

These documents contain the honours research reports for each year for the Department of Statistics.Honours Research Reports - University of Pretoria 20XXStatisticsBSs (Hons) Mathematical Statistics, BCom (Hons) Statistics, BCom (Hons) Mathematical StatisticsUnrestricte

Unmet goals of tracking: within-track heterogeneity of students' expectations for

Educational systems are often characterized by some form(s) of ability grouping, like tracking. Although substantial variation in the implementation of these practices exists, it is always the aim to improve teaching efficiency by creating homogeneous groups of students in terms of capabilities and performances as well as expected pathways. If students’ expected pathways (university, graduate school, or working) are in line with the goals of tracking, one might presume that these expectations are rather homogeneous within tracks and heterogeneous between tracks. In Flanders (the northern region of Belgium), the educational system consists of four tracks. Many students start out in the most prestigious, academic track. If they fail to gain the necessary credentials, they move to the less esteemed technical and vocational tracks. Therefore, the educational system has been called a 'cascade system'. We presume that this cascade system creates homogeneous expectations in the academic track, though heterogeneous expectations in the technical and vocational tracks. We use data from the International Study of City Youth (ISCY), gathered during the 2013-2014 school year from 2354 pupils of the tenth grade across 30 secondary schools in the city of Ghent, Flanders. Preliminary results suggest that the technical and vocational tracks show more heterogeneity in student’s expectations than the academic track. If tracking does not fulfill the desired goals in some tracks, tracking practices should be questioned as tracking occurs along social and ethnic lines, causing social inequality

Space Communications: Theory and Applications. Volume 3: Information Processing and Advanced Techniques. A Bibliography, 1958 - 1963

Annotated bibliography on information processing and advanced communication techniques - theory and applications of space communication