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Search Results: 1 - 10 of 219557 matches for " Isobel C Gormley "
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Model Based Clustering for Mixed Data: clustMD
Damien McParland,Isobel Claire Gormley
Statistics , 2015,
Abstract: A model based clustering procedure for data of mixed type, clustMD, is developed using a latent variable model. It is proposed that a latent variable, following a mixture of Gaussian distributions, generates the observed data of mixed type. The observed data may be any combination of continuous, binary, ordinal or nominal variables. clustMD employs a parsimonious covariance structure for the latent variables, leading to a suite of six clustering models that vary in complexity and provide an elegant and unified approach to clustering mixed data. An expectation maximisation (EM) algorithm is used to estimate clustMD; in the presence of nominal data a Monte Carlo EM algorithm is required. The clustMD model is illustrated by clustering simulated mixed type data and prostate cancer patients, on whom mixed data have been recorded.
Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome
Melissa J Morine, Jolene McMonagle, Sinead Toomey, Clare M Reynolds, Aidan P Moloney, Isobel C Gormley, Peadar ó Gaora, Helen M Roche
BMC Bioinformatics , 2010, DOI: 10.1186/1471-2105-11-499
Abstract: Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p < 0.05), followed by muscle (601 genes) and adipose (16 genes). Results from modified GSEA showed that the high-CLA beef diet affected diverse biological processes across the three tissues, and that the majority of pathway changes reached significance only with the bi-directional test. Combining the liver tissue microarray results with plasma marker data revealed 110 CLA-sensitive genes showing strong canonical correlation with one or more plasma markers of metabolic health, and 9 significantly overrepresented pathways among this set; each of these pathways was also significantly changed by the high-CLA diet. Closer inspection of two of these pathways - selenoamino acid metabolism and steroid biosynthesis - illustrated clear diet-sensitive changes in constituent genes, as well as strong correlations between gene expression and plasma markers of metabolic syndrome independent of the dietary effect.Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest cor
Probabilistic principal component analysis for metabolomic data
Gift Nyamundanda, Lorraine Brennan, Isobel Gormley
BMC Bioinformatics , 2010, DOI: 10.1186/1471-2105-11-571
Abstract: Here, probabilistic principal component analysis (PPCA) which addresses some of the limitations of PCA, is reviewed and extended. A novel extension of PPCA, called probabilistic principal component and covariates analysis (PPCCA), is introduced which provides a flexible approach to jointly model metabolomic data and additional covariate information. The use of a mixture of PPCA models for discovering the number of inherent groups in metabolomic data is demonstrated. The jackknife technique is employed to construct confidence intervals for estimated model parameters throughout. The optimal number of principal components is determined through the use of the Bayesian Information Criterion model selection tool, which is modified to address the high dimensionality of the data.The methods presented are illustrated through an application to metabolomic data sets. Jointly modeling metabolomic data and covariates was successfully achieved and has the potential to provide deeper insight to the underlying data structure. Examination of confidence intervals for the model parameters, such as loadings, allows for principled and clear interpretation of the underlying data structure. A software package called MetabolAnalyze, freely available through the R statistical software, has been developed to facilitate implementation of the presented methods in the metabolomics field.Metabolomics is the term used to describe the study of small molecules or metabolites present in biological samples. Examples of such metabolites include lipids, amino acids, bile acids, keto-acids. Studies of the concentration levels of these molecules in biological samples aim to enhance understanding of the effect of a particular stimulus or treatment [1-3]. The most commonly applied analytical technologies to metabolomic studies are nuclear magnetic resonance spectroscopy (NMR) [4] and mass spectrometry (MS) [5]. With respect to NMR-based metabolomics the data are usually in the form of spectra which are bin
A mixture of experts model for rank data with applications in election studies
Isobel Claire Gormley,Thomas Brendan Murphy
Statistics , 2009, DOI: 10.1214/08-AOAS178
Abstract: A voting bloc is defined to be a group of voters who have similar voting preferences. The cleavage of the Irish electorate into voting blocs is of interest. Irish elections employ a ``single transferable vote'' electoral system; under this system voters rank some or all of the electoral candidates in order of preference. These rank votes provide a rich source of preference information from which inferences about the composition of the electorate may be drawn. Additionally, the influence of social factors or covariates on the electorate composition is of interest. A mixture of experts model is a mixture model in which the model parameters are functions of covariates. A mixture of experts model for rank data is developed to provide a model-based method to cluster Irish voters into voting blocs, to examine the influence of social factors on this clustering and to examine the characteristic preferences of the voting blocs. The Benter model for rank data is employed as the family of component densities within the mixture of experts model; generalized linear model theory is employed to model the influence of covariates on the mixing proportions. Model fitting is achieved via a hybrid of the EM and MM algorithms. An example of the methodology is illustrated by examining an Irish presidential election. The existence of voting blocs in the electorate is established and it is determined that age and government satisfaction levels are important factors in influencing voting in this election.
A dynamic probabilistic principal components model for the analysis of longitudinal metabolomic data
Gift Nyamundanda,Isobel Claire Gormley,Lorraine Brennan
Statistics , 2013,
Abstract: In a longitudinal metabolomics study, multiple metabolites are measured from several observations at many time points. Interest lies in reducing the dimensionality of such data and in highlighting influential metabolites which change over time. A dynamic probabilistic principal components analysis (DPPCA) model is proposed to achieve dimension reduction while appropriately modelling the correlation due to repeated measurements. This is achieved by assuming an autoregressive model for some of the model parameters. Linear mixed models are subsequently used to identify influential metabolites which change over time. The proposed model is used to analyse data from a longitudinal metabolomics animal study.
Transcriptomic Coordination in the Human Metabolic Network Reveals Links between n-3 Fat Intake, Adipose Tissue Gene Expression and Metabolic Health
Melissa J. Morine,Audrey C. Tierney,Ben van Ommen,Hannelore Daniel,Sinead Toomey,Ingrid M. F. Gjelstad,Isobel C. Gormley,Pablo Pérez-Martinez,Christian A. Drevon,Jose López-Miranda,Helen M. Roche
PLOS Computational Biology , 2011, DOI: 10.1371/journal.pcbi.1002223
Abstract: Understanding the molecular link between diet and health is a key goal in nutritional systems biology. As an alternative to pathway analysis, we have developed a joint multivariate and network-based approach to analysis of a dataset of habitual dietary records, adipose tissue transcriptomics and comprehensive plasma marker profiles from human volunteers with the Metabolic Syndrome. With this approach we identified prominent co-expressed sub-networks in the global metabolic network, which showed correlated expression with habitual n-3 PUFA intake and urinary levels of the oxidative stress marker 8-iso-PGF2α. These sub-networks illustrated inherent cross-talk between distinct metabolic pathways, such as between triglyceride metabolism and production of lipid signalling molecules. In a parallel promoter analysis, we identified several adipogenic transcription factors as potential transcriptional regulators associated with habitual n-3 PUFA intake. Our results illustrate advantages of network-based analysis, and generate novel hypotheses on the transcriptomic link between habitual n-3 PUFA intake, adipose tissue function and oxidative stress.
On Estimation of Parameter Uncertainty in Model-Based Clustering
Adrian O'Hagan,Thomas Brendan Murphy,Isobel Claire Gormley
Statistics , 2015,
Abstract: Mixture models are a popular tool in model-based clustering. Such a model is often fitted by a procedure that maximizes the likelihood, such as the EM algorithm. At convergence, the maximum likelihood parameter estimates are typically reported, but in most cases little emphasis is placed on the variability associated with these estimates. In part this may be due to the fact that standard errors are not directly calculated in the model-fitting algorithm, either because they are not required to fit the model, or because they are difficult to compute. The examination of standard errors in model-based clustering is therefore typically neglected. The widely used R package mclust has recently introduced bootstrap and weighted likelihood bootstrap methods to facilitate standard error estimation. This paper provides an empirical comparison of these methods (along with the jackknife method) for producing standard errors and confidence intervals for mixture parameters. These methods are illustrated and contrasted in both a simulation study and in the traditional Old Faithful data set.
MetSizeR: selecting the optimal sample size for metabolomic studies using an analysis based approach
Gift Nyamundanda,Isobel Claire Gormley,Yue Fan,William M Gallagher,Lorraine Brennan
Statistics , 2013, DOI: 10.1186/1471-2105-14-338
Abstract: Background: Determining sample sizes for metabolomic experiments is important but due to the complexity of these experiments, there are currently no standard methods for sample size estimation in metabolomics. Since pilot studies are rarely done in metabolomics, currently existing sample size estimation approaches which rely on pilot data can not be applied. Results: In this article, an analysis based approach called MetSizeR is developed to estimate sample size for metabolomic experiments even when experimental pilot data are not available. The key motivation for MetSizeR is that it considers the type of analysis the researcher intends to use for data analysis when estimating sample size. MetSizeR uses information about the data analysis technique and prior expert knowledge of the metabolomic experiment to simulate pilot data from a statistical model. Permutation based techniques are then applied to the simulated pilot data to estimate the required sample size. Conclusions: The MetSizeR methodology, and a publicly available software package which implements the approach, are illustrated through real metabolomic applications. Sample size estimates, informed by the intended statistical analysis technique, and the associated uncertainty are provided.
Clustering South African households based on their asset status using latent variable models
Damien McParland,Isobel Claire Gormley,Tyler H. McCormick,Samuel J. Clark,Chodziwadziwa Whiteson Kabudula,Mark A. Collinson
Statistics , 2014, DOI: 10.1214/14-AOAS726
Abstract: The Agincourt Health and Demographic Surveillance System has since 2001 conducted a biannual household asset survey in order to quantify household socio-economic status (SES) in a rural population living in northeast South Africa. The survey contains binary, ordinal and nominal items. In the absence of income or expenditure data, the SES landscape in the study population is explored and described by clustering the households into homogeneous groups based on their asset status. A model-based approach to clustering the Agincourt households, based on latent variable models, is proposed. In the case of modeling binary or ordinal items, item response theory models are employed. For nominal survey items, a factor analysis model, similar in nature to a multinomial probit model, is used. Both model types have an underlying latent variable structure - this similarity is exploited and the models are combined to produce a hybrid model capable of handling mixed data types. Further, a mixture of the hybrid models is considered to provide clustering capabilities within the context of mixed binary, ordinal and nominal response data. The proposed model is termed a mixture of factor analyzers for mixed data (MFA-MD). The MFA-MD model is applied to the survey data to cluster the Agincourt households into homogeneous groups. The model is estimated within the Bayesian paradigm, using a Markov chain Monte Carlo algorithm. Intuitive groupings result, providing insight to the different socio-economic strata within the Agincourt region.
Sten Roer Andersen
Dan Gormley
Voices: A World Forum for Music Therapy , 2013,
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