Statistical Models Commons^™

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards …

Controlling For Confounding Via Propensity Score Methods Can Result In Biased Estimation Of The Conditional Auc: A Simulation Study, Hadiza I. Galadima, Donna K. Mcclish

Community & Environmental Health Faculty Publications

In the medical literature, there has been an increased interest in evaluating association between exposure and outcomes using nonrandomized observational studies. However, because assignments to exposure are not random in observational studies, comparisons of outcomes between exposed and nonexposed subjects must account for the effect of confounders. Propensity score methods have been widely used to control for confounding, when estimating exposure effect. Previous studies have shown that conditioning on the propensity score results in biased estimation of conditional odds ratio and hazard ratio. However, research is lacking on the performance of propensity score methods for covariate adjustment when estimating the …

Variable Selection In Accelerated Failure Time (Aft) Frailty Models: An Application Of Penalized Quasi-Likelihood, Sarbesh R. Pandeya

College of Graduate Studies: Theses & Dissertations

Variable selection is one of the standard ways of selecting models in large scale datasets. It has applications in many fields of research study, especially in large multi-center clinical trials. One of the prominent methods in variable selection is the penalized likelihood, which is both consistent and efficient. However, the penalized selection is significantly challenging under the influence of random (frailty) covariates. It is even more complicated when there is involvement of censoring as it may not have a closed-form solution for the marginal log-likelihood. Therefore, we applied the penalized quasi-likelihood (PQL) approach that approximates the solution for such a …

Bayesian Hierarchical Meta-Analysis Of Asymptomatic Ebola Seroprevalence, Peter Brody-Moore

CMC Senior Theses

The continued study of asymptomatic Ebolavirus infection is necessary to develop a more complete understanding of Ebola transmission dynamics. This paper conducts a meta-analysis of eight studies that measure seroprevalence (the number of subjects that test positive for anti-Ebolavirus antibodies in their blood) in subjects with household exposure or known case-contact with Ebola, but that have shown no symptoms. In our two random effects Bayesian hierarchical models, we find estimated seroprevalences of 8.76% and 9.72%, significantly higher than the 3.3% found by a previous meta-analysis of these eight studies. We also produce a variation of this meta-analysis where we exclude …

Methods For Evaluating Dropout Attrition In Survey Data, Camille J. Hochheimer

Theses and Dissertations

As researchers increasingly use web-based surveys, the ease of dropping out in the online setting is a growing issue in ensuring data quality. One theory is that dropout or attrition occurs in phases that can be generalized to phases of high dropout and phases of stable use. In order to detect these phases, several methods are explored. First, existing methods and user-specified thresholds are applied to survey data where significant changes in the dropout rate between two questions is interpreted as the start or end of a high dropout phase. Next, survey dropout is considered as a time-to-event outcome and …

Statistical Modeling Of Influenza-Like-Illness In Montana Using Spatial And Temporal Methods, Benjamin A. Stark

Graduate Student Theses, Dissertations, & Professional Papers

Studying air pollution and public health has been a historically important question in science. It has long been hypothesized that severe air pollution conditions lead to negative implications in basic human health. Primarily, areas thats are prone to severe degrees of human pollution are the focus of such studies. Such research relating to less populated areas are scarce, and this scarcity raises the question of how such pollution dynamics (human-made and natural) influence human health in more rural areas.

The aim of this study is to explore this hole in research; in particular we explore possible links between air pollution …

Generalized Spatiotemporal Modeling And Causal Inference For Assessing Treatment Effects For Multiple Groups For Ordinal Outcome., Soutik Ghosal

Electronic Theses and Dissertations

This dissertation consists of three projects and can be categorized in two broad research areas: generalized spatiotemporal modeling and causal inference based on observational data. In the first project, I introduce a Bayesian hierarchical mixed effect hurdle model with a nested random effect structure to model the count for primary care providers and understand their spatial and temporal variation. This study further enables us to identify the health professional shortage areas and the possible impacting factors. In the second project, I have unified popular parametric and nonparametric propensity score-based methods to assess the treatment effect of multiple groups for ordinal …

Association Tests For Genetic Effect And Its Interaction With Environmental Factors, Zhengyang Zhou

Statistical Science Theses and Dissertations

My research is in the area of statistical genetics, and it contains three projects: (1) Differentiating the Cochran-Armitage (CA) trend test and Pearson’s chi-square test: location and dispersion; (2) Decomposing Pearson’s chi-square test: a linear regression and its departure from linearity; (3) Testing nonlinear gene-environment (GxE) interaction through varying coefficient and linear mixed models.

(1) In genetic case-control association studies, a standard practice is to perform the CA trend test with 1 degree-of-freedom (df) under the assumption of an additive model. However, when the true genetic model is recessive or near recessive, it is outperformed by Pearson’s chi-square test with …

Developing Statistical Methods For Data From Platforms Measuring Gene Expression, Gaoxiang Jia

Statistical Science Theses and Dissertations

This research contains two topics: (1) PBNPA: a permutation-based non-parametric analysis of CRISPR screen data; (2) RCRnorm: an integrated system of random-coefficient hierarchical regression models for normalizing NanoString nCounter data from FFPE samples.

Clustered regularly-interspaced short palindromic repeats (CRISPR) screens are usually implemented in cultured cells to identify genes with critical functions. Although several methods have been developed or adapted to analyze CRISPR screening data, no single spe- cific algorithm has gained popularity. Thus, rigorous procedures are needed to overcome the shortcomings of existing algorithms. We developed a Permutation-Based Non-Parametric Analysis (PBNPA) algorithm, which computes p-values at the gene level …

Incorporating Historical Models With Adaptive Bayesian Updates, Philip S. Boonstra, Ryan P. Barbaro

The University of Michigan Department of Biostatistics Working Paper Series

This paper considers Bayesian approaches for incorporating information from a historical model into a current analysis when the historical model includes only a subset of covariates currently of interest. The statistical challenge is two-fold. First, the parameters in the nested historical model are not generally equal to their counterparts in the larger current model, neither in value nor interpretation. Second, because the historical information will not be equally informative for all parameters in the current analysis, additional regularization may be required beyond that provided by the historical information. We propose several novel extensions of the so-called power prior that adaptively …

The Impact Of Truncating Data On The Predictive Ability For Single-Step Genomic Best Linear Unbiased Prediction, Jeremy T. Howard, Thomas A. Rathje, Caitlyn E. Bruns, Danielle F. Wilson-Wells, Stephen D. Kachman, Matthew L. Spangler

Department of Animal Science: Faculty Publications

Simulated and swine industry data sets were utilized to assess the impact of removing older data on the predictive ability of selection candidate estimated breeding values (EBV) when using single-step genomic best linear unbiased prediction (ssGBLUP). Simulated data included thirty replicates designed to mimic the structure of swine data sets. For the simulated data, varying amounts of data were truncated based on the number of ancestral generations back from the selection candidates. The swine data sets consisted of phenotypic and genotypic records for three traits across two breeds on animals born from 2003 to 2017. Phenotypes and genotypes were iteratively …

Improved Methods And Selecting Classification Types For Time-Dependent Covariates In The Marginal Analysis Of Longitudinal Data, I-Chen Chen

Theses and Dissertations--Epidemiology and Biostatistics

Generalized estimating equations (GEE) are popularly utilized for the marginal analysis of longitudinal data. In order to obtain consistent regression parameter estimates, these estimating equations must be unbiased. However, when certain types of time-dependent covariates are presented, these equations can be biased unless an independence working correlation structure is employed. Moreover, in this case regression parameter estimation can be very inefficient because not all valid moment conditions are incorporated within the corresponding estimating equations. Therefore, approaches using the generalized method of moments or quadratic inference functions have been proposed for utilizing all valid moment conditions. However, we have found that …

Penalized Mixed-Effects Ordinal Response Models For High-Dimensional Genomic Data In Twins And Families, Amanda E. Gentry

Theses and Dissertations

The Brisbane Longitudinal Twin Study (BLTS) was being conducted in Australia and was funded by the US National Institute on Drug Abuse (NIDA). Adolescent twins were sampled as a part of this study and surveyed about their substance use as part of the Pathways to Cannabis Use, Abuse and Dependence project. The methods developed in this dissertation were designed for the purpose of analyzing a subset of the Pathways data that includes demographics, cannabis use metrics, personality measures, and imputed genotypes (SNPs) for 493 complete twin pairs (986 subjects.) The primary goal was to determine what combination of SNPs and …

Statistical Methods For Analyzing Multivariate Phenotypes And Detecting Rare Variant Associations, Huanhuan Zhu

Dissertations, Master's Theses and Master's Reports

This dissertation includes four papers with each distributed in one chapter.

In chapter 1, I compared the performance of eight multivariate phenotype association tests. The motivation to conduct this power comparison paper is as follows. For nearly 15 years, genome-wide association studies (GWAS) have been widely used to identify genetic variants associated with human diseases and traits. GWAS typically investigate genetic variants for a predefined phenotype, thus fail to identify weak but important effects. In recent years, many multivariate association tests have been developed. However, there is a lack of comprehensive summary of such kinds of approaches. To fill this …

Estimating The Respiratory Lung Motion Model Using Tensor Decomposition On Displacement Vector Field, Kingston Kang

Theses and Dissertations

Modern big data often emerge as tensors. Standard statistical methods are inadequate to deal with datasets of large volume, high dimensionality, and complex structure. Therefore, it is important to develop algorithms such as low-rank tensor decomposition for data compression, dimensionality reduction, and approximation.

With the advancement in technology, high-dimensional images are becoming ubiquitous in the medical field. In lung radiation therapy, the respiratory motion of the lung introduces variabilities during treatment as the tumor inside the lung is moving, which brings challenges to the precise delivery of radiation to the tumor. Several approaches to quantifying this uncertainty propose using a …

Seasonal Resource Selection And Habitat Treatment Use By A Fringe Population Of Greater Sage-Grouse, Rhett Boswell

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Movement and habitat selection by Greater Sage-grouse (Centrocercus uropasianus) is of great interest to wildlife managers tasked with applying conservation measures for this iconic western species. Current technology has created small and lightweight GPS (Global Positioning Systems) transmitters that can be attached to sage-grouse. Using GIS software and statistical programs such as Program R, land managers can analyze GPS location data to assess how sage-grouse are geospatially interacting with their habitats. Within the Panguitch Sage-Grouse Management Area (SGMA) thousands of acres of land have been restored or manipulated to enhance sage-grouse habitat; this usually involves removal of pinyon pine …

Application Of Support Vector Machine Modeling And Graph Theory Metrics For Disease Classification, Jessica M. Rudd

Published and Grey Literature from PhD Candidates

Disease classification is a crucial element of biomedical research. Recent studies have demonstrated that machine learning techniques, such as Support Vector Machine (SVM) modeling, produce similar or improved predictive capabilities in comparison to the traditional method of Logistic Regression. In addition, it has been found that social network metrics can provide useful predictive information for disease modeling. In this study, we combine simulated social network metrics with SVM to predict diabetes in a sample of data from the Behavioral Risk Factor Surveillance System. In this dataset, Logistic Regression outperformed SVM with ROC index of 81.8 and 81.7 for models with …

Testing The Independence Hypothesis Of Accepted Mutations For Pairs Of Adjacent Amino Acids In Protein Sequences, Jyotsna Ramanan, Peter Revesz

School of Computing: Faculty Publications

Evolutionary studies usually assume that the genetic mutations are independent of each other. However, that does not imply that the observed mutations are independent of each other because it is possible that when a nucleotide is mutated, then it may be biologically beneficial if an adjacent nucleotide mutates too. With a number of decoded genes currently available in various genome libraries and online databases, it is now possible to have a large-scale computer-based study to test whether the independence assumption holds for pairs of adjacent amino acids. Hence the independence question also arises for pairs of adjacent amino acids within …

Visualizing Lab And Phenotype Associations Using Phewas And Electronic Health Records, Brenda Emerson, Miriam Goldman, Sahiti Kolli

Honors Projects

As the digitization of patient health records is becoming more common, we are given a great opportunity to analyze these records and hopefully make discoveries about diseases or medicines. Being given large datasets of Electronic Health Records, I and two other students decided to look for novel phenotype associations with mean lab values, look to see whether the presence of a lab had associations with a phenotype, and create an interactive application to visual the associations between labs and phenotypes.

Burden Of Atopic Dermatitis In The United States: Analysis Of Healthcare Claims Data In The Commercial, Medicare, And Medi-Cal Databases, Sulena Shrestha, Raymond Miao, Li Wang, Jingdong Chao, Huseyin Yuce, Wenhui Wei

Publications and Research

Comparative data on the burden of atopic dermatitis (AD) in adults relative to the general population are limited. We performed a large-scale evaluation of the burden of disease among US adults with AD relative to matched non-AD controls, encompassing comorbidities, healthcare resource utilization (HCRU), and costs, using healthcare claims data. The impact of AD disease severity on these outcomes was also evaluated.

Mixture Models For Undiagnosed Prevalent Disease And Interval-Censored Incident Disease: Applications To A Cohort Assembled From Electronic Health Records., Li C Cheung, Qing Pan, Noorie Hyun, Mark Schiffman, Barbara Fetterman, Philip E Castle, Thomas Lorey, Hormuzd A Katki

Epidemiology Faculty Publications

For cost-effectiveness and efficiency, many large-scale general-purpose cohort studies are being assembled within large health-care providers who use electronic health records. Two key features of such data are that incident disease is interval-censored between irregular visits and there can be pre-existing (prevalent) disease. Because prevalent disease is not always immediately diagnosed, some disease diagnosed at later visits are actually undiagnosed prevalent disease. We consider prevalent disease as a point mass at time zero for clinical applications where there is no interest in time of prevalent disease onset. We demonstrate that the naive Kaplan-Meier cumulative risk estimator underestimates risks at early …

Comparison Of Survival Curves Between Cox Proportional Hazards, Random Forests, And Conditional Inference Forests In Survival Analysis, Brandon Weathers

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Survival analysis methods are a mainstay of the biomedical fields but are finding increasing use in other disciplines including finance and engineering. A widely used tool in survival analysis is the Cox proportional hazards regression model. For this model, all the predicted survivor curves have the same basic shape, which may not be a good approximation to reality. In contrast the Random Survival Forests does not make the proportional hazards assumption and has the flexibility to model survivor curves that are of quite different shapes for different groups of subjects. We applied both techniques to a number of publicly available …

A Comparison Of Statistical Methods Relating Pairwise Distance To A Binary Subject-Level Covariate, Rachael Stone

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

A community ecologist provided a motivating data set involving a certain animal species with two behavior groups, along with a pairwise genetic distance matrix among individuals. Many community ecologists have analyzed similar data sets with a method known as the Hopkins method, testing for an association between the subject-level covariate (behavior group) and the pairwise distance. This community ecologist wanted to know if they used the Hopkins method, would their results be meaningful? Their question inspired this thesis work, where a different data set was used for confidentiality reasons. Multiple methods (Hopkins method, ADONIS, ANOSIM, and Distance Regression) were used …

Statistical Methods For Two Problems In Cancer Research: Analysis Of Rna-Seq Data From Archival Samples And Characterization Of Onset Of Multiple Primary Cancers, Jialu Li

Dissertations and Theses (Open Access)

My dissertation is focused on quantitative methodology development and application for two important topics in translational and clinical cancer research.

The first topic was motivated by the challenge of applying transcriptome sequencing (RNA-seq) to formalin-fixation and paraffin-embedding (FFPE) tumor samples for reliable diagnostic development. We designed a biospecimen study to directly compare gene expression results from different protocols to prepare libraries for RNA-seq from human breast cancer tissues, with randomization to fresh-frozen (FF) or FFPE conditions. To comprehensively evaluate the FFPE RNA-seq data quality for expression profiling, we developed multiple computational methods for assessment, such as the uniformity and continuity …

Network Exploration Of Correlated Multivariate Protein Data For Alzheimer's Disease Association, Matthew J. Lane

Theses

Alzheimer Disease (AD) is difficult to diagnose by using genetic testing or other traditional methods. Unlike diseases with simple genetic risk components, there exists no single marker determining as to whether someone will develop AD. Furthermore, AD is highly heterogeneous and different subgroups of individuals develop the disease due to differing factors. Traditional diagnostic methods using perceivable cognitive deficiencies are often too little too late due to the brain having suffered damage from decades of disease progression. In order to observe AD at early stages prior to the observation of cognitive deficiencies, biomarkers with greater accuracy are required. By using …

The Battle Against Malaria: A Teachable Moment, Randy K. Schwartz

Journal of Humanistic Mathematics

Malaria has been humanity’s worst public health problem throughout recorded history. Mathematical methods are needed to understand which factors are relevant to the disease and to develop counter-measures against it. This article and the accompanying exercises provide examples of those methods for use in lower- or upper-level courses dealing with probability, statistics, or population modeling. These can be used to illustrate such concepts as correlation, causation, conditional probability, and independence. The article explains how the apparent link between sickle cell trait and resistance to malaria was first verified in Uganda using the chi-squared probability distribution. It goes on to explain …

Further Advances For The Sequential Multiple Assignment Randomized Trial (Smart), Tianjiao Dai

Dissertations and Theses (Open Access)

ABSTRACT

FURTHER ADVANCES FOR THE SEQUENTIAL MULTIPLE ASSIGNMENT RANDOMIZED TRIAL (SMART)

Tianjiao Dai, M.S.

Advisory Professor: Sanjay Shete, Ph.D.

Sequential multiple assignment randomized trial (SMART) designs have been developed these years for studying adaptive interventions. In my Ph.D. study, I mainly investigate how to further improve SMART designs and optimize the interventions for each individual in the trial. My dissertation has focused on two topics of SMART designs.

1) Developing a novel SMART design that can reduce the cost and side effects associated with the interventions and proposing the corresponding analytic methods. I have developed a time-varying SMART design in …

On The Three Dimensional Interaction Between Flexible Fibers And Fluid Flow, Bogdan Nita, Ryan Allaire

Department of Mathematics Faculty Scholarship and Creative Works

In this paper we discuss the deformation of a flexible fiber clamped to a spherical body and immersed in a flow of fluid moving with a speed ranging between 0 and 50 cm/s by means of three dimensional numerical simulation developed in COMSOL . The effects of flow speed and initial configuration angle of the fiber relative to the flow are analyzed. A rigorous analysis of the numerical procedure is performed and our code is benchmarked against well established cases. The flow velocity and pressure are used to compute drag forces upon the fiber. Of particular interest is the behavior …

Optimized Variable Selection Via Repeated Data Splitting, Marinela Capanu, Colin B. Begg, Mithat Gonen

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

We introduce a new variable selection procedure that repeatedly splits the data into two sets, one for estimation and one for validation, to obtain an empirically optimized threshold which is then used to screen for variables to include in the final model. Simulation results show that the proposed variable selection technique enjoys superior performance compared to candidate methods, being amongst those with the lowest inclusion of noisy predictors while having the highest power to detect the correct model and being unaffected by correlations among the predictors. We illustrate the methods by applying them to a cohort of patients undergoing hepatectomy …

Novel Models Of Visual Topographic Map Alignment In The Superior Colliculus., Ruben A Tikidji-Hamburyan, Tarek A El-Ghazawi, Jason W. Triplett

Pediatrics Faculty Publications

The establishment of precise neuronal connectivity during development is critical for sensing the external environment and informing appropriate behavioral responses. In the visual system, many connections are organized topographically, which preserves the spatial order of the visual scene. The superior colliculus (SC) is a midbrain nucleus that integrates visual inputs from the retina and primary visual cortex (V1) to regulate goal-directed eye movements. In the SC, topographically organized inputs from the retina and V1 must be aligned to facilitate integration. Previously, we showed that retinal input instructs the alignment of V1 inputs in the SC in a manner dependent on …