Statistics and Probability Commons^™

James-Stein Type Compound Estimation Of Multiple Mean Response Functions And Their Derivatives, Limin Feng

Theses and Dissertations--Statistics

Charnigo and Srinivasan originally developed compound estimators to nonparametrically estimate mean response functions and their derivatives simultaneously when there is one response variable and one covariate. The compound estimator maintains self consistency and almost optimal convergence rate. This dissertation studies, in part, compound estimation with multiple responses and/or covariates. An empirical comparison of compound estimation, local regression and spline smoothing is included, and near optimal convergence rates are established in the presence of multiple covariates.

James and Stein proposed an estimator of the mean vector of a p dimensional multivariate normal distribution, which produces a smaller risk than the maximum …

Polytopes Arising From Binary Multi-Way Contingency Tables And Characteristic Imsets For Bayesian Networks, Jing Xi

Theses and Dissertations--Statistics

The main theme of this dissertation is the study of polytopes arising from binary multi-way contingency tables and characteristic imsets for Bayesian networks.

Firstly, we study on three-way tables whose entries are independent Bernoulli ran- dom variables with canonical parameters under no three-way interaction generalized linear models. Here, we use the sequential importance sampling (SIS) method with the conditional Poisson (CP) distribution to sample binary three-way tables with the sufficient statistics, i.e., all two-way marginal sums, fixed. Compared with Monte Carlo Markov Chain (MCMC) approach with a Markov basis (MB), SIS procedure has the advantage that it does not require …

Mapping And Decomposing Scale-Dependent Soil Moisture Variability Within An Inner Bluegrass Landscape, Carla Landrum

Theses and Dissertations--Plant and Soil Sciences

There is a shared desire among public and private sectors to make more reliable predictions, accurate mapping, and appropriate scaling of soil moisture and associated parameters across landscapes. A discrepancy often exists between the scale at which soil hydrologic properties are measured and the scale at which they are modeled for management purposes. Moreover, little is known about the relative importance of hydrologic modeling parameters as soil moisture fluctuates with time. More research is needed to establish which observation scales in space and time are optimal for managing soil moisture variation over large spatial extents and how these scales are …

A Support Vector Machine Based Test For Incongruence Between Sets Of Trees In Tree Space, David C. Haws, Peter Huggins, Eric M. O'Neill, David W. Weisrock, Ruriko Yoshida

Statistics Faculty Publications

BACKGROUND: The increased use of multi-locus data sets for phylogenetic reconstruction has increased the need to determine whether a set of gene trees significantly deviate from the phylogenetic patterns of other genes. Such unusual gene trees may have been influenced by other evolutionary processes such as selection, gene duplication, or horizontal gene transfer.

RESULTS: Motivated by this problem we propose a nonparametric goodness-of-fit test for two empirical distributions of gene trees, and we developed the software GeneOut to estimate a p-value for the test. Our approach maps trees into a multi-dimensional vector space and then applies support vector machines (SVMs) …

Families Or Unrelated: The Evolving Debate In Genetic Association Studies, David W. Fardo, Richard Charnigo, Michael P. Epstein

Biostatistics Faculty Publications

To help uncover the genetic determinants of complex disease, a scientist often designs an association study using either unrelated subjects or family members within pedigrees. But which of these two subject recruitment paradigms is preferable? This editorial addresses the debate over the relative merits of family- and population-based genetic association studies. We begin by briefly recounting the evolution of genetic epidemiology and the rich crossroads of statistics and genetics. We then detail the arguments for the two aforementioned paradigms in recent and current applications. Finally, we speculate on how the debate may progress with the emergence of next-generation sequencing technologies.

Genetic Association Studies Of Copy-Number Variation: Should Assignment Of Copy Number States Precede Testing?, Patrick Breheny, Prabhakar Chalise, Anthony Batzler, Liewei Wang, Brooke L. Fridley

Biostatistics Faculty Publications

Recently, structural variation in the genome has been implicated in many complex diseases. Using genomewide single nucleotide polymorphism (SNP) arrays, researchers are able to investigate the impact not only of SNP variation, but also of copy-number variants (CNVs) on the phenotype. The most common analytic approach involves estimating, at the level of the individual genome, the underlying number of copies present at each location. Once this is completed, tests are performed to determine the association between copy number state and phenotype. An alternative approach is to carry out association testing first, between phenotype and raw intensities from the SNP array …

Analysis Of Binary Data Via Spatial-Temporal Autologistic Regression Models, Zilong Wang

Theses and Dissertations--Statistics

Spatial-temporal autologistic models are useful models for binary data that are measured repeatedly over time on a spatial lattice. They can account for effects of potential covariates and spatial-temporal statistical dependence among the data. However, the traditional parametrization of spatial-temporal autologistic model presents difficulties in interpreting model parameters across varying levels of statistical dependence, where its non-negative autocovariates could bias the realizations toward 1. In order to achieve interpretable parameters, a centered spatial-temporal autologistic regression model has been developed. Two efficient statistical inference approaches, expectation-maximization pseudo-likelihood approach (EMPL) and Monte Carlo expectation-maximization likelihood approach (MCEML), have been proposed. Also, Bayesian …

Evaluating Retention In Medical Care And Its Impact On The Health Outcomes Of Individuals Living With Human Inmmunodeficiency Virus, Timothy N. Crawford

Theses and Dissertations--Epidemiology and Biostatistics

In the last few years, engagement in medical care among individuals living with HIV has become a major priority among HIV medical providers and public health researchers. Engagement in medical care is an important concept as it involves the process of linking newly diagnosed individuals into medical care and retaining those individuals in care throughout the course of their infection. Although there have been major advances in the management of HIV, like the advent of Highly Active Antiretroviral Therapy, morbidity and mortality due to HIV cannot be fully reduced if the individual does not optimally retain in care. Retention in …

The Analysis Of Image Feature Robustness Using Cometcloud, Xin Qi, Hyunjoo Kim, Fuyong Xing, Manish Parashar, David J. Foran, Lin Yang

Biostatistics Faculty Publications

The robustness of image features is a very important consideration in quantitative image analysis. The objective of this paper is to investigate the robustness of a range of image texture features using hematoxylin stained breast tissue microarray slides which are assessed while simulating different imaging challenges including out of focus, changes in magnification and variations in illumination, noise, compression, distortion, and rotation. We employed five texture analysis methods and tested them while introducing all of the challenges listed above. The texture features that were evaluated include co-occurrence matrix, center-symmetric auto-correlation, texture feature coding method, local binary pattern, and texton. Due …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Thinking Outside The Curve, Part Ii: Modeling Fetal-Infant Mortality, Richard Charnigo, Lorie W. Chesnut, Tony Lobianco, Russell S. Kirby

Statistics Faculty Publications

BACKGROUND: Greater epidemiologic understanding of the relationships among fetal-infant mortality and its prognostic factors, including birthweight, could have vast public health implications. A key step toward that understanding is a realistic and tractable framework for analyzing birthweight distributions and fetal-infant mortality. The present paper is the second of a two-part series that introduces such a framework.

METHODS: We propose estimating birthweight-specific mortality within each component of a normal mixture model representing a birthweight distribution, the number of components having been determined from the data rather than fixed a priori.

RESULTS: We address a number of methodological issues related to our …

Thinking Outside The Curve, Part I: Modeling Birthweight Distribution, Richard Charnigo, Lorie W. Chesnut, Tony Lobianco, Russell S. Kirby

Statistics Faculty Publications

BACKGROUND: Greater epidemiologic understanding of the relationships among fetal-infant mortality and its prognostic factors, including birthweight, could have vast public health implications. A key step toward that understanding is a realistic and tractable framework for analyzing birthweight distributions and fetal-infant mortality. The present paper is the first of a two-part series that introduces such a framework.

METHODS: We propose describing a birthweight distribution via a normal mixture model in which the number of components is determined from the data using a model selection criterion rather than fixed a priori.

RESULTS: We address a number of methodological issues, including how the …

Nonparametric Estimation Of Derivatives With Applications, Benjamin Hall

University of Kentucky Doctoral Dissertations

We review several nonparametric regression techniques and discuss their various strengths and weaknesses with an emphasis on derivative estimation and confidence band creation. We develop a generalized C(p) criterion for tuning parameter selection when interest lies in estimating one or more derivatives and the estimator is both linear in the observed responses and self-consistent. We propose a method for constructing simultaneous confidence bands for the mean response and one or more derivatives, where simultaneous now refers both to values of the covariate and to all derivatives under consideration. In addition we generalize the simultaneous confidence bands to account for heteroscedastic …

A Markov Transition Model To Dementia With Death As A Competing Event, Liou Xu

University of Kentucky Doctoral Dissertations

The research on multi-state Markov transition model is motivated by the nature of the longitudinal data from the Nun Study (Snowdon, 1997), and similar information on the BRAiNS cohort (Salazar, 2004). Our goal is to develop a flexible methodology for handling the categorical longitudinal responses and competing risks time-to-event that characterizes the features of the data for research on dementia. To do so, we treat the survival from death as a continuous variable rather than defining death as a competing absorbing state to dementia. We assume that within each subject the survival component and the Markov process are linked by …

Comparison Of Two Samples By A Nonparametric Likelihood-Ratio Test, William H. Barton

University of Kentucky Doctoral Dissertations

In this dissertation we present a novel computational method, as well as its software implementation, to compare two samples by a nonparametric likelihood-ratio test. The basis of the comparison is a mean-type hypothesis. The software is written in the R-language [4]. The two samples are assumed to be independent. Their distributions, which are assumed to be unknown, may be discrete or continuous. The samples may be uncensored, right-censored, left-censored, or doubly-censored. Two software programs are offered. The first program covers the case of a single mean-type hypothesis. The second program covers the case of multiple mean-type hypotheses. For the first …

On Quality Control Measures In Genome-Wide Association Studies: A Test To Assess The Genotyping Quality Of Individual Probands In Family-Based Association Studies And An Application To The Hapmap Data, David W. Fardo, Iuliana Ionita-Laza, Christoph Lange

Biostatistics Faculty Publications

Allele transmissions in pedigrees provide a natural way of evaluating the genotyping quality of a particular proband in a family-based, genome-wide association study. We propose a transmission test that is based on this feature and that can be used for quality control filtering of genome-wide genotype data for individual probands. The test has one degree of freedom and assesses the average genotyping error rate of the genotyped SNPs for a particular proband. As we show in simulation studies, the test is sufficiently powerful to identify probands with an unreliable genotyping quality that cannot be detected with standard quality control filters. …

Statistical Methods In Microarray Data Analysis, Liping Huang

University of Kentucky Doctoral Dissertations

This dissertation includes three topics. First topic: Regularized estimation in the AFT model with high dimensional covariates. Second topic: A novel application of quantile regression for identification of biomarkers exemplified by equine cartilage microarray data. Third topic: Normalization and analysis of cDNA microarray using linear contrasts.

Focus On Rna Isolation: Obtaining Rna For Microrna (Mirna) Expression Profiling Analyses Of Neural Tissue, Wang-Xia Wang, Bernard R. Wilfred, Donald A. Baldwin, R. Benjamin Isett, Na Ren, Arnold J. Stromberg, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are present in all known plant and animal tissues and appear to be somewhat concentrated in the mammalian nervous system. Many different miRNA expression profiling platforms have been described. However, relatively little research has been published to establish the importance of 'upstream' variables in RNA isolation for neural miRNA expression profiling. We tested whether apparent changes in miRNA expression profiles may be associated with tissue processing, RNA isolation techniques, or different cell types in the sample. RNA isolation was performed on a single brain sample using eight different RNA isolation methods, and results were correlated using a conventional …

On The Optimality Of The Neighbor-Joining Algorithm, Kord Eickmeyer, Peter Huggins, Lior Pachter, Ruriko Yoshida

Statistics Faculty Publications

The popular neighbor-joining (NJ) algorithm used in phylogenetics is a greedy algorithm for finding the balanced minimum evolution (BME) tree associated to a dissimilarity map. From this point of view, NJ is "optimal" when the algorithm outputs the tree which minimizes the balanced minimum evolution criterion. We use the fact that the NJ tree topology and the BME tree topology are determined by polyhedral subdivisions of the spaces of dissimilarity maps R(n2)+ to study the optimality of the neighbor-joining algorithm. In particular, we investigate and compare the polyhedral subdivisions for n ≤ 8. This requires the measurement of volumes of …

The Expression Of Microrna Mir-107 Decreases Early In Alzheimer's Disease And May Accelerate Disease Progression Through Regulation Of Β-Site Amyloid Precursor Protein-Cleaving Enzyme 1, Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with …

Phylogenetic Methods For Testing Significant Codivergence Between Host Species And Their Symbionts, Skyler Speakman

University of Kentucky Master's Theses

Significant phylogenetic codivergence between plant or animal hosts (H) and their symbionts or parasites (P) indicate the importance of their interactions on evolutionary time scales. However, valid and realistic methods to test for codivergence are not fully developed. One of the systems where possible codivergence has been of interest involves the large subfamily of temperate grasses (Pooideae) and their endophytic fungi (epichloae). Here we introduce the MRCALink (most-recent-common-ancestor link) method and use it to investigate the possibility of grass-epichloё codivergence. MRCALink applied to ultrametric H and P trees identifies all corresponding nodes for pairwise comparisons of …

Empirical Processes And Roc Curves With An Application To Linear Combinations Of Diagnostic Tests, Costel Chirila

University of Kentucky Doctoral Dissertations

The Receiver Operating Characteristic (ROC) curve is the plot of Sensitivity vs. 1- Specificity of a quantitative diagnostic test, for a wide range of cut-off points c. The empirical ROC curve is probably the most used nonparametric estimator of the ROC curve. The asymptotic properties of this estimator were first developed by Hsieh and Turnbull (1996) based on strong approximations for quantile processes. Jensen et al. (2000) provided a general method to obtain regional confidence bands for the empirical ROC curve, based on its asymptotic distribution.

Since most biomarkers do not have high enough sensitivity and specificity to …

Gene Expression Patterns That Predict Sensitivity To Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors In Lung Cancer Cell Lines And Human Lung Tumors, Justin M. Balko, Anil Potti, Christopher Saunders, Arnold J. Stromberg, Eric B. Haura, Esther P. Black

Statistics Faculty Publications

BACKGROUND: Increased focus surrounds identifying patients with advanced non-small cell lung cancer (NSCLC) who will benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). EGFR mutation, gene copy number, coexpression of ErbB proteins and ligands, and epithelial to mesenchymal transition markers all correlate with EGFR TKI sensitivity, and while prediction of sensitivity using any one of the markers does identify responders, individual markers do not encompass all potential responders due to high levels of inter-patient and inter-tumor variability. We hypothesized that a multivariate predictor of EGFR TKI sensitivity based on gene expression data would offer a …