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Inferential Methods for High-Throughput Methylation DataCapparuccini, Maria 23 November 2010 (has links)
The role of abnormal DNA methylation in the progression of disease is a growing area of research that relies upon the establishment of sound statistical methods. The common method for declaring there is differential methylation between two groups at a given CpG site, as summarized by the difference between proportions methylated db=b1-b2, has been through use of a Filtered Two Sample t-test, using the recommended filter of 0.17 (Bibikova et al., 2006b). In this dissertation, we performed a re-analysis of the data used in recommending the threshold by fitting a mixed-effects ANOVA model. It was determined that the 0.17 filter is not accurate and conjectured that application of a Filtered Two Sample t-test likely leads to loss of power. Further, the Two Sample t-test assumes that data arise from an underlying distribution encompassing the entire real number line, whereas b1 and b2 are constrained on the interval . Additionally, the imposition of a filter at a level signifying the minimum level of detectable difference to a Two Sample t-test likely reduces power for smaller but truly differentially methylated CpG sites. Therefore, we compared the Two Sample t-test and the Filtered Two Sample t-test, which are widely used but largely untested with respect to their performance, to three proposed methods. These three proposed methods are a Beta distribution test, a Likelihood ratio test, and a Bootstrap test, where each was designed to address distributional concerns present in the current testing methods. It was ultimately shown through simulations comparing Type I and Type II error rates that the (unfiltered) Two Sample t-test and the Beta distribution test performed comparatively well.
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The evolutionary genetics of behavioural variation : multivariate perspectives on personality in the Trinidadian guppyWhite, Stephen John January 2017 (has links)
Animal personality is found in a wide range of taxa, yet our knowledge of what maintains consistent among-individual variation in behaviour is still incomplete. Many personality traits are associated with fitness, leading to the expectation that, under selection, genetic (and among-individual) variation will be eroded over time. Several adaptive models have been developed in order to explain this maintenance of variation. These include state-dependence, state-behaviour feedback loops, life-history and behavioural coadaptation and the Pace of Life syndrome. These models represent good starting points for thinking about what drives and maintains among-individual variation in behaviour, and while empirical support for these models is mixed, one thing they do have in common is the assumption of a significant genetic basis underpinning personality traits. Significant heritability is required for an evolutionary response to selection and for among-individual variation to be adaptive. The univariate estimates of heritability for personality traits that are growing in the literature, while useful, are likely insufficient to predict how personality traits will respond to selection. This thesis uses the Trinidadian guppy, Poecilia reticulata, and other species to explore patterns of among-individual and genetic variation in personality traits, advocating the benefits of using multivariate perspectives throughout. Firstly, the among-individual covariance structure between measures of boldness, growth and metabolic rate are estimated in a test of the Pace of Life syndrome. Secondly, an appraisal of the relative strength of maternal and genetic effects on offspring personality and how it changes over ontogeny. Next, a comprehensive treatment of sexual dimorphism in behaviour and size followed by analysis of genotype-by-sex interactions using both univariate and multivariate methods. Finally, a comparative analysis of personality in 7 species of small fish, identifying the main axis of among-individual variation from a single assay in each and quantifying the phylogenetic signal.
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Modelling Human Risk of West Nile Virus Using Surveillance and Environmental DataMallya, Shruti January 2017 (has links)
Limited research has been performed in Ontario to ascertain risk factors for West Nile Virus (WNV) and to develop a unified risk prediction strategy. The aim of the current body of work was to use spatio-temporal modelling in conjunction with surveillance and environmental data to determine which pre-WNV season factors could forecast a high risk season and to explore how well mosquito surveillance data could predict human cases in space and time during the WNV season. Generalized linear mixed modelling found that mean minimum monthly temperature variables and annual WNV-positive mosquito pools were most significantly predictive of number of human WNV cases (p<0.001). Spatio-temporal cluster analysis found that positive mosquito pool clusters could predict human case clusters up to one month in advance. These results demonstrate the usefulness of mosquito surveillance data as well as publicly available climate data for assessing risk and informing public health practice.
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Investigating the response of subtropical forests to environmental variation through the study of the Abies kawakamii treelines in TaiwanGreenwood, Sarah January 2014 (has links)
Altitudinal treeline advance represents a sensitive and well-studied example of species response to climate warming. Although a great deal of work has been conducted globally, few studies have considered subtropical alpine treelines and little is known about their structure and function. This research aims to investigate the response of high altitude forests in Taiwan to climate variation by characterising treeline advance in the area, exploring the mechanisms driving the advance, and considering the consequences of advance for the wider community. The thesis consists of a general introduction to the topic followed by a series of papers, exploring: (1) Possible consequences of treeline shifts for biodiversity and ecosystem function. (2) The advance of the Abies kawakamii treeline through aerial photograph analysis. (3) The changes in growth rate of Abies kawakamii at treeline and the influence of altitude and temperature on growth. (4) Regeneration patterns at treeline and the importance of microclimate and topographic sheltering. (5) Consequences of the range shift for the wider forest community. The work is then concluded with a general discussion and synthesis. The main aims of this work are therefore to characterise and understand the pattern and pace of treeline advance and forest structural change throughout the Central Mountain Range of Taiwan. Treeline advance is characterised through the study of repeat aerial photographs and the mechanisms behind the observed shift are explored through the study of two key responses associated with forest advance: tree growth at treeline and seedling establishment beyond treeline. The consequences of treeline advance for the wider subalpine community are investigated through the study of epiphytic lichen communities at treeline sites. This investigation of an understudied region will allow for improved understanding of treeline response at a global scale.
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