Biostatistics Commons^™

Genetic Contributors Of Incident Stroke In 10,700 African Americans With Hypertension: A Meta-Analysis From The Genetics Of Hypertension Associated Treatments And Reasons For Geographic And Racial Differences In Stroke Studies, Nicole D. Armstrong, Vinodh Srinivasasainagendra, Amit Patki, Rikki M. Tanner, Bertha A. Hidalgo, Hemant K. Tiwari, Nita A. Limdi, Ethan M. Lange, Leslie A. Lange, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals.

Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs …

Characterizing Long Covid: Deep Phenotype Of A Complex Condition, Rachel R. Deer, Madeline A. Rock, Nicole Vasilevsky, Leigh Carmody, Halie Rando, Alfred J. Anzalone, Marc D. Basson, Tellen D. Bennett, Timothy Bergquist, Eilis A. Boudreau, Carolyn T. Bramante, James Brian Byrd, Tiffany J. Callahan, Lauren E. Chan, Haitao Chu, Christopher G. Chute, Ben D. Coleman, Hannah E. Davis, Joel Gagnier, Casey S. Greene, Ramakanth Kavuluru

Institute for Biomedical Informatics Faculty Publications

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies.

METHODS: The Human Phenotype Ontology …

Verrucous Carcinoma Of The Vulva: Patterns Of Care And Treatment Outcomes., Sara M. Dryden, Leonid B. Reshko, Jeremy T. Gaskins, Scott R. Silva

Faculty and Staff Scholarship

Background: Verrucous vulvar carcinoma (VC) is an uncommon and distinct histologic subtype of squamous cell carcinoma (SCC). The available literature on VC is currently limited to case reports and small single institution studies. Aims: The goals of this study were to analyze data from the National Cancer Database (NCDB) to quantitate the incidence of VC and to investigate the effects of patient demographics, tumor characteristics, and treatment regimens on overall survival (OS) in women with verrucous vulvar carcinoma. Methods and results: Patients diagnosed with vulvar SCC or VC between the years of 2004 and 2016 were identified in the NCDB. …

Pattern Of Use Of Electronic Health Record (Ehr) Among The Chronically Ill: A Health Information National Trend Survey (Hints) Analysis, Rose Calixte, Sumaiya Islam, Zainab Toteh Osakwe, Argelis Rivera, Marlene Camacho-Rivera

Publications and Research

Effective patient–provider communication is a cornerstone of patient-centered care. Patient portals provide an effective method for secure communication between patients or their proxies and their health care providers. With greater acceptability of patient portals in private practices, patients have a unique opportunity to manage their health care needs. However, studies have shown that less than 50% of patients reported accessing the electronic health record (EHR) in a 12-month period. We used HINTS 5 cycle 1 and cycle 2 to assess disparities among US residents 18 and older with any chronic condition regarding the use of EHR for secure direct messaging …

Gene Selection And Classification In High-Throughput Biological Data With Integrated Machine Learning Algorithms And Bioinformatics Approaches, Abhijeet R Patil

Open Access Theses & Dissertations

With the rise of high throughput technologies in biomedical research, large volumes of expression profiling, methylation profiling, and RNA-sequencing data are being generated. These high-dimensional data have large number of features with small number of samples, a characteristic called the "curse of dimensionality." The selection of optimal features, which largely affects the performance of classification algorithms in machine learning models, has led to challenging problems in bioinformatics analyses of such high-dimensional datasets. In this work, I focus on the design of two-stage frameworks of feature selection and classification and their applications in multiple sets of colorectal cancer data. The first …

Understanding The Effect Of Adaptive Mutations On The Three-Dimensional Structure Of Rna, Justin Cook

Undergraduate Research and Scholarship Symposium

Single-nucleotide polymorphisms (SNPs) are variations in the genome where one base pair can differ between individuals.¹ SNPs occur throughout the genome and can correlate to a disease-state if they occur in a functional region of DNA.¹According to the central dogma of molecular biology, any variation in the DNA sequence will have a direct effect on the RNA sequence and will potentially alter the identity or conformation of a protein product. A single RNA molecule, due to intramolecular base pairing, can acquire a plethora of 3-D conformations that are described by its structural ensemble. One SNP, rs12477830, which …

Taxonomic Annotation Of Near-Coral Seawater Microbiota In Kilifi, Kenya, Megan Ruoff

Independent Study Project (ISP) Collection

The general objective of this study was to analyze the microbiome of seawater above a coral reef in Kilifi, Kenya. Specific objectives included establishing a baseline microbiota profile, classifying the identified organisms at various taxonomic levels, and conjecturing about reef health from the presence or absence of bioindicator species including Vibrio bacteria. Sequenced 16S rRNA gene sequences from seawater samples at Kuruwitu Conservancy in Kilifi, Kenya were taxonomically classified by exact matching employing the Dada2 software package and the naïve Bayesian classifier method with 97% similarity cut off. The seawater microbiota contained mostly Proteobacteria (73.28%), followed by Bacteroidetes (14.08%) and …

Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan

Biostatistics Faculty Publications

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure …

The Causes And Control Measures Of Extended Spectrum Beta-Lactamase Producing Enterobacteriaceae In Long-Term Care Facilities, Ismaila Olatunji Sule

Walden Dissertations and Doctoral Studies

Due to extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), infections among residents are increasing in long-term care facilities (LTCFs), resulting in high rate of morbidity and healthcare costs. ESBL-PE resists empirical antibiotics and reduces treatment options, and a designated infection control team is unavailable to prevent the prevalence of the disease. Ecological theory guided this study. A systematic review and meta-analysis were conducted to characterize the causes of ESBL-PE and evaluate the infection control strategies within LTCFs. Multiple regression analysis (MRA) was included as supplementary statistical analysis to identify relationships between LTCFs, geographical locations, infection control measures (ICMs), and ESBL-PE. A systematic search …

Ensemble Protein Inference Evaluation, Kyle Lee Lucke

Graduate Student Theses, Dissertations, & Professional Papers

The Protein inference problem is becoming an increasingly important tool that aids in the characterization of complex proteomes and analysis of complex protein samples. In bottom-up shotgun proteomics experiments the metrics for evaluation (like AUC and calibration error) are based on an often imperfect target-decoy database. These metrics make the inherent assumption that all of the proteins in the target set are present in the sample being analyzed. In general, this is not the case, they are typically a mix of present and absent proteins. To objectively evaluate inference methods, protein standard datasets are used. These datasets are special in …

Impact Of Case Management On Childhood Lead Exposure In Marion County, Indiana, Maliki Yacouba

Walden Dissertations and Doctoral Studies

The Centers for Disease Control and Prevention recently declared that no amount of childhood blood lead level (BLL) is safe. The purpose of this quantitative study with a retrospective cohort design was to evaluate the effectiveness of case management intervention on children diagnosed with elevated BLL (EBLL; ≥ 5 μg/dL) in Marion, County, Indiana. The health belief model was used as the theoretical foundation for the study. A data set of 160 lead exposure case management records was analyzed to find whether: (a) BLL at post-case-management time significantly differ from BLL at baseline (b) BLL at post-case-management time is affected …

Gene Set Testing By Distance Correlation, Sho-Hsien Su

Graduate Theses and Dissertations

Pathways are the functional building blocks of complex diseases such as cancers. Pathway-level studies may provide insights on some important biological processes. Gene set test is an important tool to study the differential expression of a gene set between two groups, e.g., cancer vs normal. The differential expression of a gene set could be due to the difference in mean, variability, or both. However, most existing gene set tests only target the mean difference but overlook other types of differential expression. In this thesis, we propose to use the recently developed distance correlation for gene set testing. To assess the …

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 …

Machine Learning Applications For Drug Repurposing, Hansaim Lim

Dissertations, Theses, and Capstone Projects

The cost of bringing a drug to market is astounding and the failure rate is intimidating. Drug discovery has been of limited success under the conventional reductionist model of one-drug-one-gene-one-disease paradigm, where a single disease-associated gene is identified and a molecular binder to the specific target is subsequently designed. Under the simplistic paradigm of drug discovery, a drug molecule is assumed to interact only with the intended on-target. However, small molecular drugs often interact with multiple targets, and those off-target interactions are not considered under the conventional paradigm. As a result, drug-induced side effects and adverse reactions are often neglected …

Effect Of Zinc On Microcystis Aeruginosa And Its Toxin Production, Jose L. Perez

Seton Hall University Dissertations and Theses (ETDs)

Cyanobacteria harmful algal blooms (CHABs) are globally increasing biomasses of detrimental cyanobacteria due to anthropogenic water phosphorous and nitrogen loading and climate change. CHABs often produce secondary metabolites, cyanotoxins, that cause harmful effects to organisms, most water systems, and socioeconomic infrastructures. Additionally, the presence of heavy metal pollutant runoff in CHAB affected environments may result in CHAB population changes – aggravating toxigenicity. Zinc metal resistance and stress response were studied in microcystin (MC) cyanotoxin-producing Microcystis aeruginosa UTEX LB 2385 (M. aeruginosa UTEX LB 2385) and non-MC producing Microcystis aeruginosa UTEX LB 2386 (M. aeruginosa UTEX LB 2386) cyanobacteria. Molecular analysis …

Spatial And Temporal Genetic Structure Of Winter-Run Steelhead (Oncorhynchus Mykiss) Returning To The Mad River, California, Steven R. Fong

Cal Poly Humboldt theses and projects

Distinct populations of steelhead in the wild are in decline. The propagation of steelhead in hatcheries has been used to boost population numbers for recreational fisheries and for use in conservation. However, hatchery breeding practices of steelhead can result in changes in genetic structure. I investigated the genetic structure of winter-run steelhead (Oncorhynchus mykiss) returning to the Mad River, California, where a hatchery has been used enhance production for recreational fisheries since 1971. Genetic variability in Mad River steelhead was evaluated using 96 single nucleotide polymorphisms (SNPs) among 4203 individuals, including the Mad River and nearby locations, and …

Enhancing Timeliness Of Drug Overdose Mortality Surveillance: A Machine Learning Approach, Patrick J. Ward, Peter J. Rock, Svetla Slavova, April M. Young, Terry L. Bunn, Ramakanth Kavuluru

Kentucky Injury Prevention and Research Center Faculty Publications

BACKGROUND: Timely data is key to effective public health responses to epidemics. Drug overdose deaths are identified in surveillance systems through ICD-10 codes present on death certificates. ICD-10 coding takes time, but free-text information is available on death certificates prior to ICD-10 coding. The objective of this study was to develop a machine learning method to classify free-text death certificates as drug overdoses to provide faster drug overdose mortality surveillance.

METHODS: Using 2017–2018 Kentucky death certificate data, free-text fields were tokenized and features were created from these tokens using natural language processing (NLP). Word, bigram, and trigram features were created …

36 Years After The Species' Mass-Mortality: Diadema Antillarum Test Sizes, Population Densities, And Substrate Preferences In Three Guna Yala Reefs Near Wichub Wala Island, Bimini Horstmann

Independent Study Project (ISP) Collection

In January 1983, a waterborne pathogen beginning near the Atlantic Panama Canal entrance caused history's largest recorded marine animal die-off, wiping out 95-99% of Diadema antillarum populations throughout the Caribbean. D. antillarum, the long-spined sea urchin, is a keystone herbivore in coral reefs and its decreased densities have caused many reefs to suffer macroalgal phase shifts. Modest recovery of this species has been documented in some Caribbean locations, but reefs in Guna Yala, Panama continued to experience population decline. This study investigates density, test size, and substrate preferences of D. antillarum in three shallow coral reef areas to update the …

Optimizing Water Quality And Temperature Parameters To Increase Survival Rates Of Anotheca Spinosa (Anura: Hylidae) Eggs At The El Valle Amphibian Conservation Center, Morgan Oestereich

Independent Study Project (ISP) Collection

Amphibians globally are facing extinction due to the fungus Batrachochytrium dendrobatidis (Bd). This has resulted in a worldwide push for increased conservation efforts. These efforts include those of the El Valle Amphibian Conservation Center (EVACC) in El Valle de Antón, Panama, where captive assurance colonies of many native amphibian species are housed. Among these species is Anotheca spinosa, a species of tree frog native to mountainous regions of Central America. This study was performed to analyze the relationship between water quality parameters and egg survival and reproductive success of EVACC’s captive population of A. spinosa and assess how related husbandry …

From Traps To Snapshots: Examining The Ecology Of Feral Predators And Native Small Mammals In Southeastern Australia Through Case Studies Of Two Faunal Sampling Methods, Katherine Karson

Independent Study Project (ISP) Collection

The red fox (Vulpes vulpes) and feral cat (Felis catus) are introduced mesopredators that significantly threaten native small mammal species in Australia. For decades, environmental managers have attempted to mitigate the effects of these introduced species. However, ecosystems are highly complex, making it difficult to assess the impacts of feral predators on communities of native fauna independent of other disturbances such as fire regime and habitat fragmentation. Cost-effective ecological monitoring programs are imperative for evaluating threats to native species and informing environmental decisions. New technology has become increasingly present in wildlife monitoring, and camera trapping has provided an alternative to …

An Analysis Of The Rajasthan Public Health System’S Response To The 2019 Dengue Insurgence, Luke Bryan

Independent Study Project (ISP) Collection

Dengue virus is in a pandemic status and is a major public health issue in the modern world. The mosquito-borne disease is largely prevalent in Asia and specifically India, where more than half of the states are considered to have complete presence of the dengue virus. The intricate infrastructure of the Indian public health system looks for dengue cases at all levels and reports to the integrated disease surveillance programme (IDSP).

Analyses of the IDSP and trends of dengue cases was done in response to dengue outbreaks throughout the state. Geographic information system (GIS) maps were created to evaluate a …

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 …

Data Analytics Pipeline For Rna Structure Analysis Via Shape, Quinn Nelson

UNO Student Research and Creative Activity Fair

Coxsackievirus B3 (CVB3) is a cardiovirulent enterovirus from the family Picornaviridae. The RNA genome houses an internal ribosome entry site (IRES) in the 5’ untranslated region (5’UTR) that enables cap-independent translation. Ample evidence suggests that the structure of the 5’UTR is a critical element for virulence. We probe RNA structure in solution using base-specific modifying agents such as dimethyl sulfate as well as backbone targeting agents such as N-methylisatoic anhydride used in Selective 2’-Hydroxyl Acylation Analyzed by Primer Extension (SHAPE). We have developed a pipeline that merges and evaluates base-specific and SHAPE data together with statistical analyses that provides confidence …

Impact Of The Affordable Care Act On Colorectal Cancer Screening, Incidence, And Survival In Kentucky, Tong Gan, Heather F. Sinner, Samuel C. Walling, Quan Chen, Bin Huang, Thomas C. Tucker, Jitesh A. Patel, B. Mark Evers, Avinash S. Bhakta

Surgery Faculty Publications

Background

Kentucky ranks first in the US in cancer incidence and mortality. Compounded by high poverty levels and a high rate of medically uninsured, cancer rates are even worse in Appalachian Kentucky. Being one of the first states to adopt the Affordable Care Act (ACA) Medicaid expansion, insurance coverage markedly increased for Kentucky residents. The purpose of our study was to determine the impact of Medicaid expansion on colorectal cancer (CRC) screening, diagnosis, and survival in Kentucky.

Study Design

The Kentucky Cabinet for Health and Family Services and the Kentucky Cancer Registry were queried for individuals (≥20 years) undergoing CRC …

Gene Co-Expression Networks Analysis Reveal Novel Molecular Endotypes In Alpha-1 Antitrypsin Deficiency, Jen-Hwa Chu, Wenlan Zang

Yale Day of Data

Rationale:Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that predisposes to early onset pulmonary emphysema and airways obstruction. The exact mechanism through which AATD leads to lung disease is incompletely understood.

Objectives: To investigate the effect of AAT genotype and augmentation therapy on bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) transcriptome, while examining the link between gene expression profiles, and clinical features of AATD.

Methods: We performed RNA-Seq on RNA extracted from BAL and PBMC on samples obtained from 89 AATD patients enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Differential …

A Novel Pathway-Based Distance Score Enhances Assessment Of Disease Heterogeneity In Gene Expression, Yunqing Liu, Xiting Yan

Yale Day of Data

Distance-based unsupervised clustering of gene expression data is commonly used to identify heterogeneity in biologic samples. However, high noise levels in gene expression data and the relatively high correlation between genes are often encountered, so traditional distances such as Euclidean distance may not be effective at discriminating the biological differences between samples. In this study, we developed a novel computational method to assess the biological differences based on pathways by assuming that ontologically defined biological pathways in biologically similar samples have similar behavior. Application of this distance score results in more accurate, robust, and biologically meaningful clustering results in both …

Combination Of Resampling Based Lasso Feature Selection And Ensembles Of Regularized Regression Models, Abhijeet R. Patil

Open Access Theses & Dissertations

In high-dimensional data, the performance of various classiers is largely dependent on the selection of important features. Most of the individual classiers using existing feature selection (FS) methods do not perform well for highly correlated data. Obtaining important

features using the FS method and selecting the best performing classier is a challenging task in high throughput data. In this research, we propose a combination of resampling based least absolute shrinkage and selection operator (LASSO) feature selection (RLFS)

and ensembles of regularized regression models (ERRM) capable of handling data with the high correlation structures. The ERRM boosts the prediction accuracy with …

Methods For Joint Normalization And Comparison Of Hi-C Data, John C. Stansfield

Theses and Dissertations

The development of chromatin conformation capture technology has opened new avenues of study into the 3D structure and function of the genome. Chromatin structure is known to influence gene regulation, and differences in structure are now emerging as a mechanism of regulation between, e.g., cell differentiation and disease vs. normal states. Hi-C sequencing technology now provides a way to study the 3D interactions of the chromatin over the whole genome. However, like all sequencing technologies, Hi-C suffers from several forms of bias stemming from both the technology and the DNA sequence itself. Several normalization methods have been developed for normalizing …

Statistical Methods For Joint Analysis Of Multiple Phenotypes And Their Applications For Phewas, Xueling Li

Dissertations, Master's Theses and Master's Reports

Genome-wide association studies (GWAS) have successfully detected tens of thousands of robust SNP-trait associations. Earlier researches have primarily focused on association studies of genetic variants and some well-defined functions or phenotypic traits. Emerging evidence suggests that pleiotropy, the phenomenon of one genetic variant affects multiple phenotypes, is widespread, especially in complex human diseases. Therefore, individual phenotype analyses may lose statistical power to identify the underlying genetic mechanism. Contrasting with single phenotype analyses, joint analysis of multiple phenotypes exploits the correlations between phenotypes and aggregates multiple weak marginal effects and is therefore likely to provide new insights into the functional consequences …