Physical Sciences and Mathematics Commons^™

Exploration And Comparison Of Methods For Combining Population- And Family-Based Genetic Association Using The Genetic Analysis Workshop 17 Mini-Exome, David W. Fardo, Anthony R. Druen, Jinze Liu, Lucia Mirea, Claire Infante-Rivard, Patrick Breheny

Biostatistics Faculty Publications

We examine the performance of various methods for combining family- and population-based genetic association data. Several approaches have been proposed for situations in which information is collected from both a subset of unrelated subjects and a subset of family members. Analyzing these samples separately is known to be inefficient, and it is important to determine the scenarios for which differing methods perform well. Others have investigated this question; however, no extensive simulations have been conducted, nor have these methods been applied to mini-exome-style data such as that provided by Genetic Analysis Workshop 17. We quantify the empirical power and false-positive …

Follow-Up Testing In Functional Anova, Olga A. Vsevolozhskaya, Mark C. Greenwood

Olga A. Vsevolozhskaya

Functional analysis of variance involves testing for differences in functional means across k groups in n functional responses. If a significant overall difference in the mean curves is detected, one may want to identify the location of these differences. Two different follow-up testing methods are discussed and contrasted. A point-wise test proposed by Cox and Lee (2008) is compared to a test based on regions of the functional domain. The methods are contrasted in terms of weak control of the family-wise error rate, strong control of the family-wise error rate, and power.

Gene Set Analysis For Longitudinal Gene Expression Data, Ke Zhang, Haiyan Wang, Arne C. Bathke, Solomon W. Harrar, Hans-Peter Piepho, Youping Deng

Statistics Faculty Publications

BACKGROUND: Gene set analysis (GSA) has become a successful tool to interpret gene expression profiles in terms of biological functions, molecular pathways, or genomic locations. GSA performs statistical tests for independent microarray samples at the level of gene sets rather than individual genes. Nowadays, an increasing number of microarray studies are conducted to explore the dynamic changes of gene expression in a variety of species and biological scenarios. In these longitudinal studies, gene expression is repeatedly measured over time such that a GSA needs to take into account the within-gene correlations in addition to possible between-gene correlations.

RESULTS: We provide …

Differential Gene Expression In Liver And Small Intestine From Lactating Rats Compared To Age-Matched Virgin Controls Detects Increased Mrna Of Cholesterol Biosynthetic Genes, Antony Athippozhy, Liping Huang, Clavia Ruth Wooton-Kee, Tianyong Zhao, Paiboon Jungsuwadee, Arnold J. Stromberg, Mary Vore

Statistics Faculty Publications

BACKGROUND: Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression …

Some Contributions To The Censored Empirical Likelihood With Hazard-Type Constraints, Yanling Hu

University of Kentucky Doctoral Dissertations

Empirical likelihood (EL) is a recently developed nonparametric method of statistical inference. Owen’s 2001 book contains many important results for EL with uncensored data. However, fewer results are available for EL with right-censored data. In this dissertation, we first investigate a right-censored-data extension of Qin and Lawless (1994). They studied EL with uncensored data when the number of estimating equations is larger than the number of parameters (over-determined case). We obtain results similar to theirs for the maximum EL estimator and the EL ratio test, for the over-determined case, with right-censored data. We employ hazard-type constraints which are better able …

Parametric Estimation In Competing Risks And Multi-State Models, Yushun Lin

Theses and Dissertations--Statistics

The typical research of Alzheimer's disease includes a series of cognitive states. Multi-state models are often used to describe the history of disease evolvement. Competing risks models are a sub-category of multi-state models with one starting state and several absorbing states.

Analyses for competing risks data in medical papers frequently assume independent risks and evaluate covariate effects on these events by modeling distinct proportional hazards regression models for each event. Jeong and Fine (2007) proposed a parametric proportional sub-distribution hazard (SH) model for cumulative incidence functions (CIF) without assumptions about the dependence among the risks. We modified their model to …

Analysis Of Differential Gene Expression And Alternative Splicing In The Liver And Gastrointestinal Tract In The Lactating Rat, Antony Thomas Athippozhy

University of Kentucky Doctoral Dissertations

Rat exon microarrays were utilized to detect changes in mRNA expression and alternative splicing in the liver, duodenum, jejunum, and ileum of the lactating rat when compared to age-matched virgin controls. Analysis of data at the level of gene expression revealed differential expression of genes involved in cholesterol biosynthesis in each tissue examined, suggesting increased Sterol Response Element Binding Protein activity. We also detected decreased mRNA from components of the T-cell signaling pathway in the jejunum and ileum. We characterized expression of solute carrier and adenosine triphosphate binding cassette proteins. In addition to characterizing genes by pathway, we have also …

Bayesian Semiparametric Generalizations Of Linear Models Using Polya Trees, Angela Schoergendorfer

University of Kentucky Doctoral Dissertations

In a Bayesian framework, prior distributions on a space of nonparametric continuous distributions may be defined using Polya trees. This dissertation addresses statistical problems for which the Polya tree idea can be utilized to provide efficient and practical methodological solutions.

One problem considered is the estimation of risks, odds ratios, or other similar measures that are derived by specifying a threshold for an observed continuous variable. It has been previously shown that fitting a linear model to the continuous outcome under the assumption of a logistic error distribution leads to more efficient odds ratio estimates. We will show that deviations …

Stochastic Dynamics Of Gene Transcription, Yan Xie

Theses and Dissertations--Statistics

Gene transcription in individual living cells is inevitably a stochastic and dynamic process. Little is known about how cells and organisms learn to balance the fidelity of transcriptional control and the stochasticity of transcription dynamics. In an effort to elucidate the contribution of environmental signals to this intricate balance, a Three State Model was recently proposed, and the transcription system was assumed to transit among three different functional states randomly.

In this work, we employ this model to demonstrate how the stochastic dynamics of gene transcription can be characterized by the three transition parameters. We compute the probability distribution of …