Biostatistics Commons^™

A Persistent Homology Framework For Scrna-Seq: Assessing Clustering Robustness And Quantifying Preprocessing And Integration Effects On Topological Features., Jonah Daneshmand

Electronic Theses and Dissertations

As single-cell RNA sequencing (scRNA-seq) data expands, robust methods for integrating diverse datasets are critical. This dissertation applies Persistent Homology (PH), a technique from Topological Data Analysis (TDA), to a collection of scRNA-seq datasets spanning eight tissue types to quantify how data integration affects topological features and biological interpretability. We assessed global topological structure using Betti curves, Euler characteristics, and persistence landscapes across raw, normalized, and integrated data representations. Our analysis revealed a performance inversion: while conventional methods excelled on unintegrated data, high-granularity topological methods, particularly those sensitive to global data structure, became superior after integration. This suggests a synergy …

Evaluating Alpha Spending Functions Applied To Observational Time-To-Event Analysis, Moses Torgbenu

Electronic Theses and Dissertations

This thesis explores the theoretical foundation of the alpha spending approach and extends its application beyond the conventional setting of randomized controlled trials (RCTs) to observational studies with time to event analyses. In these less structured environments, key design parameters such as the total number of events are often unknown, posing challenges for the standard implementation of sequential analysis methods.

Through simulation studies, this research delivers several important contributions. First, it presents a modified approach that uses calendar time to define the timing of interim analyses while relying on event-based information to estimate the correlation among test statistics. This adjustment …

Predictor-Informed Bayesian Nonparametric Clustering., Md Yasin Ali Parh

Electronic Theses and Dissertations

In this dissertation, we performed clustering of observations such that the cluster membership is influenced by a set of predictors. To that end, we employ the Bayesian nonparametric Common Atom Model (CAM), which is a nested clustering algorithm that utilizes a (fixed) group membership for each observation to encourage more similar clustering of members of the same group. CAM operates by assuming each group has its own vector of cluster probabilities, which are themselves clustered to allow similar clustering for some groups. We extend this approach by treating the group membership as an unknown latent variable determined as a flexible …

New Bayesian Methods For Longitudinal Data Analysis With Complex Dependence Structures., Anish Mukherjee

Electronic Theses and Dissertations

Longitudinal data in real-world settings are frequently found to be heterogeneous and exhibit intricate spatio-temporal dependence structures. Analyzing such complex data to obtain reliable estimation while quantifying uncertainty necessitates using sophisticated Bayesian methodology. In this work, we present novel Bayesian methods developed to address these challenges. We often observe heterogeneity in longitudinal data, where the mean and variance for certain profiles meaningfully differs from the rest. Some profiles may also exhibit outliers at a limited number of measurements. Using a standard mixed effects model, which assumes homogeneity, can lead to overestimating the residual variance and inefficient estimation. In this work, …

Interactions Of The Sars-Cov-2 Viral Genome 3’-Untranslated Region With Viral And Host Rnas, Caleb Frye, Mihaela Rita Mihailescu

Electronic Theses and Dissertations

This dissertation focuses on the characterization of RNA-RNA interactions within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome and with host microRNAs. As the causative agent of coronavirus disease 2019 (COVID-19), SARS-CoV-2 has evolved rapidly since its appearance. This has warranted prompt characterization of the virus particularly of its single stranded RNA (ssRNA) genome. By using a combination of bioinformatics, biophysics, and/or biological assays, we analyzed the SARS-CoV-2 viral genomic RNA and uncovered interactions of genomic RNA with host RNAs, highlighting an underutilized method of targeting RNA viruses. We showed here that the conserved elements in the viral genomic …

The Impact Of “Multiple Looks” When Performing Survival Analysis, Quentin Eloise

Electronic Theses and Dissertations

Survival analysis is a critical statistical method in healthcare to assess patient treatment effects and disease progression. Another critical area of statistical methodology in health care is the practice of adaptive designs. Adaptive designs allow for interim analyses to take place during a study and various decisions and actions can take place more ethically. This is beneficial for studies that take multiple years to complete and allows administrators and healthcare providers to make sound decisions as early as possible. A challenging aspect of adaptive designs is that the number of interim analyses is known in advance which is applicable in …

Bayesian Approaches In Multi-State Markov Models And High Dimensional Time-To-Event Data., Yuchen Han

Electronic Theses and Dissertations

This dissertation consists of two projects. The first one involves nonparametric methods on Continuous Time Markov Chains (CTMCs). The second one is centered around Bayesian shrinkage models for detecting prognostic and predictive biomarkers in high-dimensional clinical data. Both these projects build on methods from across the frequentist and Bayesian paradigm to offer novel solutions. In the first project, we aim to model the nonlinear effects of continuous variables within multistate framework in a non-parametrically by appealing to the rich mathematical framework of Reproducing Kernel Hilbert Spaces (RKHS). Then we adapted the classical Representer Theorem to penalized (squared norm) log-likelihood which …

Exploring The Diagnostic Potential Of Radiomics-Based Pet Image Analysis For T-Stage Tumor Diagnosis, Victor Aderanti

Electronic Theses and Dissertations

Cancer is a leading cause of death globally, and early detection is crucial for better

outcomes. This research aims to improve Region Of Interest (ROI) segmentation

and feature extraction in medical image analysis using Radiomics techniques

with 3D Slicer, Pyradiomics, and Python. Dimension reduction methods, including

PCA, K-means, t-SNE, ISOMAP, and Hierarchical Clustering, were applied to highdimensional features to enhance interpretability and efficiency. The study assessed the ability of the reduced feature set to predict T-staging, an essential component of the TNM system for cancer diagnosis. Multinomial logistic regression models were developed and evaluated using MSE, AIC, BIC, and Deviance …

An Application Of An In-Depth Advanced Statistical Analysis In Exploring The Dynamics Of Depression, Sleep Deprivation, And Self-Esteem, Muslihat Gaffari

Electronic Theses and Dissertations

Depression, intertwined with sleep deprivation and self-esteem, presents a significant challenge to mental health worldwide. The research shown in this paper employs advanced statistical methodologies to unravel the complex interactions among these factors. Through log-linear homogeneous association, multinomial logistic regression, and generalized linear models, the study scrutinizes large datasets to uncover nuanced patterns and relationships. By elucidating how depression, sleep disturbances, and self-esteem intersect, the research aims to deepen understanding of mental health phenomena. The study clarifies the relationship between these variables and explores reasons for prioritizing depression research. It evaluates how statistical models, such as log-linear, multinomial logistic regression, …

Descriptions Of Interglacial Mastodons From Snowmass, Colorado, Connor White

Electronic Theses and Dissertations

The Ziegler Reservoir fossil site (ZRFS) in Colorado contains over 4000 mastodon bones that date from 140,000 to 100,000 years ago. At an elevation of ~2705 meters above sea level, ZRFS represents an alpine ecosystem dated to Marine Isotope Stage (MIS) 5. Formal descriptions of cheek teeth, mandibles, crania, and femora were completed. Statistical analyses of the upper and lower third molars, including a novel measurement of interloph(id) distances, indicate significant differences between ZRFS mastodons and Mammut pacificus, while falling within the ranges for Mammut americanum. This study agrees with the taxonomic assignment of ZRFS mastodons to Mammut …

Bayesian Strategies For Propensity Score Estimation In Causal Inference., Uthpala I. Wanigasekara

Electronic Theses and Dissertations

Causal inference is a method used in various fields to draw causal conclusions based on data. It involves using assumptions, study designs, and estimation strategies to minimize the impact of confounding variables. Propensity scores are used to estimate outcome effects, through matching methods, stratification, weighting methods, and the Covariate Balancing Propensity Score method. However, they can be sensitive to estimation techniques and can lead to unstable findings. Researchers have proposed integrating weighing with regression adjustment in parametric models to improve causal inference validity. The first project focuses on Bayesian joint and two-stage methods for propensity score analysis. Propensity score modeling …

Causal Inference For The Effect Of Continuous Treatment On Time-To-Event Outcomes And Mediation Analysis On Health Disparities In Observational Studies., Triparna Poddar

Electronic Theses and Dissertations

The dissertation comprises two projects related to causal inference based on observational data. In healthcare research, where abundant observational data such as claims data and electronic records are available, researchers often aim to study the treatment effect and the pathway of that effect. However, estimating treatment effects in observational data presents challenges due to confounding factors. The first project focuses on estimating continuous treatment effects for survival outcomes, while the second concentrates on mediation analysis, allowing the exploration of the pathway of the causal effect. Both projects involve addressing confounding variables. In the first project, I investigate estimation of the …

Proteomics And Machine Learning For Pulmonary Embolism Risk With Protein Markers, Yaa Amankwah Awuah

Electronic Theses and Dissertations

This thesis investigates protein markers linked to pulmonary embolism risk using proteomics and statistical methods, employing unsupervised and supervised machine learning techniques. The research analyzes existing datasets, identifies significant features, and observes gender differences through MANOVA. Principal Component Analysis reduces variables from 378 to 59, and Random Forest achieves 70% accuracy. These findings contribute to our understanding of pulmonary embolism and may lead to diagnostic biomarkers. MANOVA reveals significant gender differences, and applying proteomics holds promise for clinical practice and research.

Statistical Inference On Lung Cancer Screening Using The National Lung Screening Trial Data., Farhin Rahman

Electronic Theses and Dissertations

This dissertation consists of three research projects on cancer screening probability modeling. In these projects, the three key modeling parameters (sensitivity, sojourn time, transition density) for cancer screening were estimated, along with the long-term outcomes (including overdiagnosis as one outcome), the optimal screening time/age, the lead time distribution, and the probability of overdiagnosis at the future screening time were simulated to provide a statistical perspective on the effectiveness of cancer screening programs. In the first part of this dissertation, a statistical inference was conducted for male and female smokers using the National Lung Screening Trial (NLST) chest X-ray data. A …

Non-Destructive Imaging Of Phytosulfokine Trafficking In Plants Using Fiber-Optic Fluorescence Microscopy, Bernard Abakah

Electronic Theses and Dissertations

Plants secrete peptide ligands and use receptor signaling to respond to stress and control development. Understanding these phenomena is key to improving plant health and productivity for food, fiber, and energy applications. Phytosulfokine (PSK), a sulfated peptide hormone, regulates plant cell division, growth, and stress tolerance via specific phytosulfokine receptors (PSKRs). This study uses fiber-optic fluorescence microscopy to elucidate trafficking of PSK in live plants. The microscope features two-color optics and an objective lens connected to a 1-m coherent imaging fiber mounted on either a conventional upright microscope body or 5-axis positioning system (X–Y–Z plus pitch and yaw). PSK and …

Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury

Electronic Theses and Dissertations

Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …

Mathematical Models Yield Insights Into Cnns: Applications In Natural Image Restoration And Population Genetics, Ryan Cecil

Electronic Theses and Dissertations

Due to a rise in computational power, machine learning (ML) methods have become the state-of-the-art in a variety of fields. Known to be black-box approaches, however, these methods are oftentimes not well understood. In this work, we utilize our understanding of model-based approaches to derive insights into Convolutional Neural Networks (CNNs). In the field of Natural Image Restoration, we focus on the image denoising problem. Recent work have demonstrated the potential of mathematically motivated CNN architectures that learn both `geometric' and nonlinear higher order features and corresponding regularizers. We extend this work by showing that not only can geometric features …

Statistical Methods For Personalized Treatment Selection And Survival Data Analysis Based On Observational Data With High-Dimensional Covariates., Don Ramesh Dinendra Sudaraka Tholkage

Electronic Theses and Dissertations

Due to the wide availability of functional data from multiple disciplines, the studies of functional data analysis have become popular in the recent literature. However, the related development in censored survival data has been relatively sparse. In Chapter 2, we consider the problem of analyzing time-to-event data in the presence of functional predictors. We develop a conditional generalized Kaplan Meier (KM) estimator that incorporates functional predictors using kernel weights and rigorously establishes its asymptotic properties. In addition, we propose to select the optimal bandwidth based on a time-dependent Brier score. We then carry out extensive numerical studies to examine the …

Statistical Methods For Assessing Drug Interactions And Identifying Effect Modifiers Using Observational Data., Qian Xu

Electronic Theses and Dissertations

This dissertation consists of three projects related to causal inference based on observational data. In the first project, we propose a double robust to identify the effect modifiers and estimate optimal treatment. Observational studies differ from experimental studies in that assignment of subjects to treatments is not randomized but rather occurs due to natural mechanisms, which are usually hidden from the researchers. Many statistical methods to identify the treatment effect and select the optimal personalized treatment for experimental studies may not be suitable for observational studies any more. In this project, we propose a exible outcome model to select the …

Confidence Interval For The Mean Of A Beta Distribution, Sean Rangel

Electronic Theses and Dissertations

Statistical inference for the mean of a beta distribution has become increasingly popular in various fields of academic research. In this study, we developed a novel statistical model from likelihood-based techniques to evaluate various confidence interval techniques for the mean of a beta distribution. Simulation studies will be implemented to compare the performance of the confidence intervals. In addition to the development and study involving confidence intervals, we will also apply the confidence intervals to real biological data that was gathered by the Department of Biology at Stephen F. Austin State University and provide recommendations on the best practice.

Estimating Treatment Effect On Medical Cost And Examining Medical Cost Trajectory Using Splines And Change Point Techniques., Indranil Ghosh

Electronic Theses and Dissertations

In the world of growing medical needs, other than the clinical outcomes, the cost of healthcare is one of the important aspects to evaluate. The cost of treatment could act as a decisive factor on which one to choose from two equally likely effective treatment options. In literature, the most used quantity for the cost of treatment is cumulative lifetime cost since the diagnosis of a disease. While it provides a bird' eye view of the treatment cost, it fails to capture the underlying pattern of the treatment cost trajectory. We developed a marginal structural functional model (MSFM) using an …

Predictive Modeling Of Clinical Outcomes For Hospitalized Covid-19 Patients Utilizing Cytof And Clinical Data., Onajia Stubblefield

Electronic Theses and Dissertations

In December 2019, an outbreak of a novel coronavirus initiated a global pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that causes the disease coronavirus disease 2019 (COVID-19). Symptoms of infection with COVID-19 vary widely between individuals. While some infected individuals are asymptomatic, others need more extensive care and require hospitalization. Indeed, the COVID-19 pandemic was characterized by a shortage of hospital beds which presented additional complications in providing adequate care for patients. In this study, we used a combination of T cell population data collected from mass cytometry analysis and clinical markers to form a predictive …

Bayesian Variable Selection Strategies In Longitudinal Mixture Models And Categorical Regression Problems., Md Nazir Uddin

Electronic Theses and Dissertations

In this work, we seek to develop a variable screening and selection method for Bayesian mixture models with longitudinal data. To develop this method, we consider data from the Health and Retirement Survey (HRS) conducted by University of Michigan. Considering yearly out-of-pocket expenditures as the longitudinal response variable, we consider a Bayesian mixture model with $K$ components. The data consist of a large collection of demographic, financial, and health-related baseline characteristics, and we wish to find a subset of these that impact cluster membership. An initial mixture model without any cluster-level predictors is fit to the data through an MCMC …

Estimating Cumulative Incidence Rate On Interval Censored Data In An Illness-Death Model., Chen Qian

Electronic Theses and Dissertations

Phase IV clinical trials are designed to monitor long-term side effects caused overtime by the medical treatment. For instance, in advanced primary cancer treatment, childhood cancer survivors are often at risk of developing undesired events, such as cardiotoxicity, during their adulthood. Such problems could be due to their cancer or the treatment they received for their cancer such as radiation or intensive chemotherapy. Cardiotoxicity can be diagnosed with electrophysiology with measurements of fraction shortening, afterload, etc. Often the primary focus of a study could be on estimating the cumulative incidence of a particular outcome of interest such as cardiotoxicity. However, …

Observational Studies In Group Testing And Potential Applications., Alexander Christopher Noll

Electronic Theses and Dissertations

The use of group testing to identify individuals with targeted outcomes in a population can greatly improve the efficiency, speed, and cost effectiveness of testing a population for an outcome, or at least for identifying the prevalence of an outcome in a population. The implementation of causal inference techniques can provide the basis for an observational study that would allow an investigator to gather estimates for treatment effectiveness if group testing was conducted on the population in a certain way. This thesis examines a simulation of the above outlined principles in order to demonstrate a potential application for determining treatment …

Modified-Half-Normal Distribution And Different Methods To Estimate Average Treatment Effect., Jingchao Sun

Electronic Theses and Dissertations

This dissertation consists of three projects related to Modified-Half-Normal distribution and causal inference. In my first project, a new distribution called Modified-Half-Normal distribution was introduced. I explored a few of its distributional properties, the procedures for generating random samples based on Bayesian approaches, and the parameter estimation based on the method of moments. The second project deals with the problem of selection bias of average treatment effect (ATE) if we use the observational data. I combined the propensity score based inverse probability of treatment weighting (IPTW) method and the directed acyclic graph (DAG) to solve this problem. The third project …

Statistical Approaches Of Gene Set Analysis With Quantitative Trait Loci For High-Throughput Genomic Studies., Samarendra Das

Electronic Theses and Dissertations

Recently, gene set analysis has become the first choice for gaining insights into the underlying complex biology of diseases through high-throughput genomic studies, such as Microarrays, bulk RNA-Sequencing, single cell RNA-Sequencing, etc. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results. Further, the statistical structure and steps common to these approaches have not yet been comprehensively discussed, which limits their utility. Hence, a comprehensive overview of the available gene set analysis approaches used for different high-throughput genomic studies is provided. The analysis of gene sets is usually carried out based on …

Aspects Of Causal Inference., John A. Craycroft

Electronic Theses and Dissertations

Observational studies differ from experimental studies in that assignment of subjects to treatments is not randomized but rather occurs due to natural mechanisms, which are usually hidden from researchers. Yet objectives of the two studies are frequently the same: identify the causal – rather than merely associational – relationship between some treatment or exposure and an outcome. The statistical issues that arise in properly analyzing observational data for this goal are numerous and fascinating, and these issues are encompassed in the domain of causal inference. The research presented in this dissertation explores several distinct aspects of causal inference. This dissertation …

The Influence Of Environmental Variables On The Height Growth Of Loblolly Pine (Pinus Taeda) In The Western Gulf, Osakpamwan Edo-Iyasere

Electronic Theses and Dissertations

Understanding the effects of environmental factors on stand growth is important in optimizing forest management plans. This study investigated the effects of soil and climate factors on the height growth (site index) of loblolly pine (Pinus Taeda L.) using data collected from permanent plots established in intensively-managed plantations across East Texas and Western Louisiana. The Chapman-Richards model was selected as the base model to describe the height-age relationships and important soil and climate variables were incorporated into the models as model parameter coefficient adjustors. Our results showed that the most important factors for predicting site index were nitrogen …

Linear Methods For Regression With Small Sample Sizes Relative To The Number Of Variables., Rajesh Sikder

Electronic Theses and Dissertations

In data sets where there are a small number of observations but a large number of variables observed for each observation, ordinary least squares estimation cannot be used for regression models. There are many alternative including stepwise regression, penalized methods such as ridge regression and the LASSO, and methods based on derived inputs such as principal components regression and partial least squares regression. In this thesis, these five methods are described. K-fold cross validation is also discussed as a way for determining regularization parameters for each method. The performance of these methods in estimation and prediction is also examined through …