http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
Application of Bayesian Hierarchical Models in Genetic Data Analysis
Genetic data analysis has been capturing a lot of attentions for understanding the mechanism of the development and progressing of diseases like cancers, and is crucial in discovering genetic markers and treatment targets in medical research. This dissertation focuses on several important issues in genetic data analysis, graphical network modeling, feature selection, and covariance estimation. First, we develop a gene network modeling method for discrete gene expression data, produced by technologies such as serial analysis of gene expression and RNA sequencing experiment, which generate counts of mRNA transcripts in cell samples. We propose a generalized linear model to fit the discrete gene expression data and assume that the log ratios of the mean expression levels follow a Gaussian distribution. We derive the gene network structures by selecting covariance matrices of the Gaussian distribution with a hyper-inverse Wishart prior. We incorporate prior network models based on Gene Ontology information, which avails existing biological information on the genes of interest. Next, we consider a variable selection problem, where the variables have natural grouping structures, with application to analysis of chromosomal copy number data. The chromosomal copy number data are produced by molecular inversion probes experiments which measure probe-specific copy number changes. We propose a novel Bayesian variable selection method, the hierarchical structured variable se- lection (HSVS) method, which accounts for the natural gene and probe-within-gene architecture to identify important genes and probes associated with clinically relevant outcomes. We propose the HSVS model for grouped variable selection, where simultaneous selection of both groups and within-group variables is of interest. The HSVS model utilizes a discrete mixture prior distribution for group selection and group-specific Bayesian lasso hierarchies for variable selection within groups. We further provide methods for accounting for serial correlations within groups that incorporate Bayesian fused lasso methods for within-group selection. Finally, we propose a Bayesian method of estimating high-dimensional covariance matrices that can be decomposed into a low rank and sparse component. This covariance structure has a wide range of applications including factor analytical model and random effects model. We model the covariance matrices with the decomposition structure by representing the covariance model in the form of a factor analytic model where the number of latent factors is unknown. We introduce binary indicators for estimating the rank of the low rank component combined with a Bayesian graphical lasso method for estimating the sparse component. We further extend our method to a graphical factor analytic model where the graphical model of the residuals is of interest. We achieve sparse estimation of the inverse covariance of the residuals in the graphical factor model by employing a hyper-inverse Wishart prior method for a decomposable graph and a Bayesian graphical lasso method for an unrestricted graph. The electronic version of this dissertation is accessible from http://hdl.handle.net/1969.1/148056
Doctor of Philosophy Texas A & M University 2012 http://hdl.handle.net/1969.1/148056