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Full-Text Articles in Biostatistics

Theranostic Applications Of Sirna Bioconjugates In Cancer Detection And Treatment, Sunil S. Shah May 2021

Theranostic Applications Of Sirna Bioconjugates In Cancer Detection And Treatment, Sunil S. Shah

Seton Hall University Dissertations and Theses (ETDs)

Abstract

The emerging field of RNA nanotechnology has led to rapid advances in the applications of RNA in chemical biology, medicinal chemistry, and biotechnology. At the forefront of its utility is the ability to self-assemble multiple siRNAs into nanostructure formulations capable of targeting selected oncogenes and potentiating the gene therapy of malignant tumors. Self-assembled siRNA integrates multiple siRNAs within a single molecular platform for silencing multiple oncogenic mRNA targets with high precision and efficacy to potentially induce cancer cell apoptosis through the RNA interference (RNAi) pathway. Furthermore, the conjugation of siRNA self-assemblies with bio-active probes results in multi-functional theranostic (therapy ...


A Highly Predictive Microrna Panel For Determining Delayed Cerebral Vasospasm Risk Following Aneurysmal Subarachnoid Hemorrhage, Wang-Xia Wang, Joe E. Springer, Kevin Xie, David W. Fardo, Kevin W. Hatton May 2021

A Highly Predictive Microrna Panel For Determining Delayed Cerebral Vasospasm Risk Following Aneurysmal Subarachnoid Hemorrhage, Wang-Xia Wang, Joe E. Springer, Kevin Xie, David W. Fardo, Kevin W. Hatton

Sanders-Brown Center on Aging Faculty Publications

Approximately one-third of aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral vasospasm (DCV) 3–10 days after aneurysm rupture resulting in additional, permanent neurologic disability. Currently, no validated biomarker is available to determine the risk of DCV in aSAH patients. MicroRNAs (miRNAs) have been implicated in virtually all human diseases, including aSAH, and are found in extracellular biofluids including plasma and cerebrospinal fluid (CSF). We used a custom designed TaqMan Low Density Array miRNA panel to examine the levels of 47 selected brain and vasculature injury related miRNAs in CSF and plasma specimens collected from 31 patients with or without ...


Understanding The Effect Of Adaptive Mutations On The Three-Dimensional Structure Of Rna, Justin Cook May 2021

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 ...


Species In Vernal Pools: Anova, Lisa Manne May 2021

Species In Vernal Pools: Anova, Lisa Manne

Open Educational Resources

A one-way analysis of variance exercise using data on species diversities from vernal pools.Data are from vernal pools in Willowbrook Park (adjacent to College of Staten Island's campus) in spring.

The typical ANOVA gives a straightforward result (significant anova, easily-interpreted Tukey-Kramer analysis). This data set requires more nuanced interpretation, as the ANOVA is marginally significant, and Tukey-Kramer yields one significant pairwise comparison between groups. Relative lack of variation within groups explains this apparent enigma.


Epigenome-Wide Association Study Of Kidney Function Identifies Trans-Ethnic And Ethnic-Specific Loci, Charles E. Breeze, Anna Batorsky, Mi Kyeong Lee, Mindy D. Szeto, Xiaoguang Xu, Daniel L. Mccartney, Rong Jiang, Amit Patki, Holly J. Kramer, James M. Eales, Laura Raffield, Leslie Lange, Ethan Lange, Peter Durda, Yongmei Liu, Russ P. Tracy, David Van Den Berg, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Mesa Multi-Omics Working Group, Kathryn L. Evans, William E. Kraus, Donna K. Arnett Apr 2021

Epigenome-Wide Association Study Of Kidney Function Identifies Trans-Ethnic And Ethnic-Specific Loci, Charles E. Breeze, Anna Batorsky, Mi Kyeong Lee, Mindy D. Szeto, Xiaoguang Xu, Daniel L. Mccartney, Rong Jiang, Amit Patki, Holly J. Kramer, James M. Eales, Laura Raffield, Leslie Lange, Ethan Lange, Peter Durda, Yongmei Liu, Russ P. Tracy, David Van Den Berg, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Mesa Multi-Omics Working Group, Kathryn L. Evans, William E. Kraus, Donna K. Arnett

Epidemiology Faculty Publications

BACKGROUND: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach.

METHODS: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear ...


Current Trends In The Application Of Causal Inference Methods To Pooled Longitudinal Observational Infectious Disease Studies-A Protocol For A Methodological Systematic Review, Heather Hufstedler, Ellicott C. Matthay, Sabahat Rahman, Valentijn M. T. De Jong, Harlan Campbell, Paul Gustafson, Thomas Debray, Thomas Jaenisch, Lauren Maxwell, Till Barnighausen Apr 2021

Current Trends In The Application Of Causal Inference Methods To Pooled Longitudinal Observational Infectious Disease Studies-A Protocol For A Methodological Systematic Review, Heather Hufstedler, Ellicott C. Matthay, Sabahat Rahman, Valentijn M. T. De Jong, Harlan Campbell, Paul Gustafson, Thomas Debray, Thomas Jaenisch, Lauren Maxwell, Till Barnighausen

COVID-19 Publications by UMMS Authors

INTRODUCTION: Pooling (or combining) and analysing observational, longitudinal data at the individual level facilitates inference through increased sample sizes, allowing for joint estimation of study- and individual-level exposure variables, and better enabling the assessment of rare exposures and diseases. Empirical studies leveraging such methods when randomization is unethical or impractical have grown in the health sciences in recent years. The adoption of so-called "causal" methods to account for both/either measured and/or unmeasured confounders is an important addition to the methodological toolkit for understanding the distribution, progression, and consequences of infectious diseases (IDs) and interventions on IDs. In the ...


An Ensemble Of The Icluster Method To Analyze Longitudinal Lncrna Expression Data For Psoriasis Patients, Suyan Tian, Chi Wang Apr 2021

An Ensemble Of The Icluster Method To Analyze Longitudinal Lncrna Expression Data For Psoriasis Patients, Suyan Tian, Chi Wang

Internal Medicine Faculty Publications

BACKGROUND: Psoriasis is an immune-mediated, inflammatory disorder of the skin with chronic inflammation and hyper-proliferation of the epidermis. Since psoriasis has genetic components and the diseased tissue of psoriasis is very easily accessible, it is natural to use high-throughput technologies to characterize psoriasis and thus seek targeted therapies. Transcriptional profiles change correspondingly after an intervention. Unlike cross-sectional gene expression data, longitudinal gene expression data can capture the dynamic changes and thus facilitate causal inference.

METHODS: Using the iCluster method as a building block, an ensemble method was proposed and applied to a longitudinal gene expression dataset for psoriasis, with the ...


Chromosome Xq23 Is Associated With Lower Atherogenic Lipid Concentrations And Favorable Cardiometabolic Indices, Pradeep Natarajan, Akhil Pampana, Sarah E. Graham, Sanni E. Ruotsalainen, James A. Perry, Paul S. De Vries, Jai G. Broome, James P. Pirruccello, Michael C. Honigberg, Krishna Aragam, Brooke Wolford, Jennifer A. Brody, Lucinda Antonacci-Fulton, Moscati Arden, Stella Aslibekyan, Themistocles L. Assimes, Christie M. Ballantyne, Lawrence F. Bielak, Joshua C. Bis, Brian E. Cade, Donna K. Arnett Apr 2021

Chromosome Xq23 Is Associated With Lower Atherogenic Lipid Concentrations And Favorable Cardiometabolic Indices, Pradeep Natarajan, Akhil Pampana, Sarah E. Graham, Sanni E. Ruotsalainen, James A. Perry, Paul S. De Vries, Jai G. Broome, James P. Pirruccello, Michael C. Honigberg, Krishna Aragam, Brooke Wolford, Jennifer A. Brody, Lucinda Antonacci-Fulton, Moscati Arden, Stella Aslibekyan, Themistocles L. Assimes, Christie M. Ballantyne, Lawrence F. Bielak, Joshua C. Bis, Brian E. Cade, Donna K. Arnett

Epidemiology Faculty Publications

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42 ...


Age And Sex Are Associated With The Plasma Lipidome: Findings From The Goldn Study, Emily Slade, Marguerite R. Irvin, Kevin Xie, Donna K. Arnett, Steven A. Claas, Tobias Kind, David W. Fardo, Gregory A. Graf Apr 2021

Age And Sex Are Associated With The Plasma Lipidome: Findings From The Goldn Study, Emily Slade, Marguerite R. Irvin, Kevin Xie, Donna K. Arnett, Steven A. Claas, Tobias Kind, David W. Fardo, Gregory A. Graf

Biostatistics Faculty Publications

Background
Developing an understanding of the biochemistry of aging in both sexes is critical for managing disease throughout the lifespan. Lipidomic associations with age and sex have been reported, but prior studies are limited by measurements in serum rather than plasma or by participants taking lipid-lowering medications.

Methods
Our study included lipidomic data from 980 participants aged 18–87 years old from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN). Participants were off lipid-lowering medications for at least 4 weeks, and signal intensities of 413 known lipid species were measured in plasma. We examined linear age and sex associations ...


Sars-Cov-2 Transmission In Alberta, British Columbia, And Ontario, Canada, December 25, 2019, To December 1, 2020, Isaac Chun-Hai Fung, Yuen Wai Hung, Sylvia Ofori, Kamalich Muniz-Rodriguez, Po-Ying Lai, Gerardo Chowell Mar 2021

Sars-Cov-2 Transmission In Alberta, British Columbia, And Ontario, Canada, December 25, 2019, To December 1, 2020, Isaac Chun-Hai Fung, Yuen Wai Hung, Sylvia Ofori, Kamalich Muniz-Rodriguez, Po-Ying Lai, Gerardo Chowell

Biostatistics, Epidemiology, and Environmental Health Sciences Faculty Publications

Objective:

This study aimed to investigate coronavirus disease (COVID-19) epidemiology in Alberta, British Columbia, and Ontario, Canada.

Methods:

Using data through December 1, 2020, we estimated time-varying reproduction number, R t , using EpiEstim package in R, and calculated incidence rate ratios (IRR) across the 3 provinces.

Results:

In Ontario, 76% (92 745/121 745) of cases were in Toronto, Peel, York, Ottawa, and Durham; in Alberta, 82% (49 878/61 169) in Calgary and Edmonton; in British Columbia, 90% (31 142/34 699) in Fraser and Vancouver Coastal. Across 3 provinces, R t dropped to ≤ 1 after April. In Ontario ...


Validation Of Icd-10-Cm Codes For Injuries Complicating Pregnancy, Childbirth And The Puerperium: A Medical Record Review, Anna Hansen, Dana Quesinberry, Peter Akpunonu, Julia Martin, Svetla Slavova Mar 2021

Validation Of Icd-10-Cm Codes For Injuries Complicating Pregnancy, Childbirth And The Puerperium: A Medical Record Review, Anna Hansen, Dana Quesinberry, Peter Akpunonu, Julia Martin, Svetla Slavova

Kentucky Injury Prevention and Research Center Faculty Publications

INTRODUCTION: The purpose of this study was to estimate the positive predictive value (PPV) of International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes for injury, poisoning, physical or sexual assault complicating pregnancy, childbirth and the puerperium (PCP) to capture injury encounters within both hospital and emergency department claims data.

METHODS: A medical record review was conducted on a sample (n=157) of inpatient and emergency department claims from one Kentucky healthcare system from 2015 to 2017, with any diagnosis in the ICD-10-CM range O9A.2-O9A.4. Study clinicians reviewed medical records for the sampled cases and used an ...


Predictive Modeling And Estimation Of The Doubling Time Of Confirmed Cases Of Covid-19 In Niger, Ibrahim Sidi Zakari, Hadiza Galadima Mar 2021

Predictive Modeling And Estimation Of The Doubling Time Of Confirmed Cases Of Covid-19 In Niger, Ibrahim Sidi Zakari, Hadiza Galadima

Community & Environmental Health Faculty Publications

Modeling is increasingly used to assess scenarios and make projections on the future course of new coronavirus disease. This allows for better planning of care as well as a relaxation or tightening of the restrictive measures decreed by the government and the health authorities. The data analyzed in this study covers the period from March 19 to June 05, 2020 and allowed predictions of new cases of COVID-19 based on a growth model with a growth rate that changes linearly over time. In addition, we calculated and predicted the doubling time of the number of positive cases in each region ...


Sample Size Formulas For Estimating Risk Ratios With The Modified Poisson Model For Binary Outcomes, Zhenni Xue Feb 2021

Sample Size Formulas For Estimating Risk Ratios With The Modified Poisson Model For Binary Outcomes, Zhenni Xue

Electronic Thesis and Dissertation Repository

Sample size estimation is usually the first step in planning a research study. Too small a study cannot adequately address the objectives, while too large a study may waste resources or unethical. For binary outcomes, several sample size estimation methods are available based on logistic regression models, which focusing on odds ratios. In prospective studies, risk ratios are preferable for ease of interpretation and communication. In this thesis, we compared the power difference between the logistic regression model and the modified Poisson regression model via simulation studies. We then proposed sample size estimation formulas based on the modified Poisson regression ...


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 Feb 2021

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 ...


Whole-Exome Sequencing And Hipsc Cardiomyocyte Models Identify Myrip, Trappc11, And Slc27a6 Of Potential Importance To Left Ventricular Hypertrophy In An African Ancestry Population, Marguerite R. Irvin, Praful Aggarwal, Steven A. Claas, Lisa De Las Fuentes, Anh N. Do, C. Charles Gu, Andrea Matter, Benjamin S. Olson, Amit Patki, Karen Schwander, Joshua D. Smith, Vinodh Srinivasasainagendra, Hemant K. Tiwari, Amy J. Turner, Deborah A. Nickerson, Dabeeru C. Rao, Ulrich Broeckel, Donna K. Arnett Feb 2021

Whole-Exome Sequencing And Hipsc Cardiomyocyte Models Identify Myrip, Trappc11, And Slc27a6 Of Potential Importance To Left Ventricular Hypertrophy In An African Ancestry Population, Marguerite R. Irvin, Praful Aggarwal, Steven A. Claas, Lisa De Las Fuentes, Anh N. Do, C. Charles Gu, Andrea Matter, Benjamin S. Olson, Amit Patki, Karen Schwander, Joshua D. Smith, Vinodh Srinivasasainagendra, Hemant K. Tiwari, Amy J. Turner, Deborah A. Nickerson, Dabeeru C. Rao, Ulrich Broeckel, Donna K. Arnett

Epidemiology Faculty Publications

Background: Indices of left ventricular (LV) structure and geometry represent useful intermediate phenotypes related to LV hypertrophy (LVH), a predictor of cardiovascular (CV) disease (CVD) outcomes.

Methods and Results: We conducted an exome-wide association study of LV mass (LVM) adjusted to height2.7, LV internal diastolic dimension (LVIDD), and relative wall thickness (RWT) among 1,364 participants of African ancestry (AAs) in the Hypertension Genetic Epidemiology Network (HyperGEN). Both single-variant and gene-based sequence kernel association tests were performed to examine whether common and rare coding variants contribute to variation in echocardiographic traits in AAs. We then used a data-driven ...


Non-Adherence Tree Analysis (Nata)-An Adherence Improvement Framework: A Covid-19 Case Study, Ernest Edem Edifor, Regina Brown, Paul Smith, Rick Kossik Feb 2021

Non-Adherence Tree Analysis (Nata)-An Adherence Improvement Framework: A Covid-19 Case Study, Ernest Edem Edifor, Regina Brown, Paul Smith, Rick Kossik

COVID-19 Publications by UMMS Authors

Poor medication adherence is a global phenomenon that has received a significant amount of research attention yet remains largely unsolved. Medication non-adherence can blur drug efficacy results in clinical trials, lead to substantial financial losses, increase the risk of relapse and hospitalisation, or lead to death. The most common methods of measuring adherence are post-treatment measures; that is, adherence is usually measured after the treatment has begun. What the authors are proposing in this multidisciplinary study is a new technique for predicting the factors that are likely to cause non-adherence before or during medication treatment, illustrated in the context of ...


Measurement Matters: Changing Penalty Calculations Under The Hospital Acquired Condition Reduction Program (Hacrp) Cost Hospitals Millions, Olga A. Vsevolozhskaya, Karina C. Manz, Pierre M. Zephyr, Teresa M. Waters Feb 2021

Measurement Matters: Changing Penalty Calculations Under The Hospital Acquired Condition Reduction Program (Hacrp) Cost Hospitals Millions, Olga A. Vsevolozhskaya, Karina C. Manz, Pierre M. Zephyr, Teresa M. Waters

Biostatistics Faculty Publications

BACKGROUND: Since October 2014, the Centers for Medicare and Medicaid Services has penalized 25% of U.S. hospitals with the highest rates of hospital-acquired conditions under the Hospital Acquired Conditions Reduction Program (HACRP). While early evaluations of the HACRP program reported cumulative reductions in hospital-acquired conditions, more recent studies have not found a clear association between receipt of the HACRP penalty and hospital quality of care. We posit that some of this disconnect may be driven by frequent scoring updates. The sensitivity of the HACRP penalties to updates in the program's scoring methodology has not been independently evaluated.

METHODS ...


Regression Analyses Assessing The Impact Of Environmental Factors On Covid-19 Transmission And Mortality, El Hussain Shamsa, Kezhong Zhang Feb 2021

Regression Analyses Assessing The Impact Of Environmental Factors On Covid-19 Transmission And Mortality, El Hussain Shamsa, Kezhong Zhang

Medical Student Research Symposium

No abstract provided.


Identification And Robust Estimation Of Swapped Direct And Indirect Effects: Mediation Analysis With Unmeasured Mediator–Outcome Confounding And Intermediate Confounding, An-Shun Tai, Sheng-Hsuan Lin Jan 2021

Identification And Robust Estimation Of Swapped Direct And Indirect Effects: Mediation Analysis With Unmeasured Mediator–Outcome Confounding And Intermediate Confounding, An-Shun Tai, Sheng-Hsuan Lin

Harvard University Biostatistics Working Paper Series

Counterfactual-model-based mediation analysis can yield substantial insight into the causal mechanism through the assessment of natural direct effects (NDEs) and natural indirect effects (NIEs). However, the assumptions regarding unmeasured mediator–outcome confounding and intermediate mediator–outcome confounding that are required for the determination of NDEs and NIEs present practical challenges. To address this problem, we introduce an instrumental blocker, a novel quasi-instrumental variable, to relax both of these assumptions, and we define a swapped direct effect (SDE) and a swapped indirect effect (SIE) to assess the mediation. We show that the SDE and SIE are identical to the NDE and ...


Mental Health And Psychosocial Functioning In Recently Separated U.S. Women Veterans: Trajectories And Bi-Directional Relationships, Karen A. Lawrence, Dawne Vogt, Adam Dugan, Shawn R. Nigam, Emily Slade, Brian N. Smith Jan 2021

Mental Health And Psychosocial Functioning In Recently Separated U.S. Women Veterans: Trajectories And Bi-Directional Relationships, Karen A. Lawrence, Dawne Vogt, Adam Dugan, Shawn R. Nigam, Emily Slade, Brian N. Smith

Social Work Faculty Publications

Prior research on the relationship between veterans’ mental health and psychosocial functioning has primarily relied on male samples. Here, we investigated prospective longitudinal relationships between mental health and psychosocial functioning in 554 female Iraq and Afghanistan War veterans who were surveyed three times between two- and seven-years following separation from service. Mixed effects modeling revealed that increasing depression and posttraumatic stress disorder (PTSD) severity predicted declines in work functioning. Increasing PTSD severity predicted declining parental functioning and worsening depression predicted a decline in relationship functioning. In turn, decreased work and intimate relationship functioning predicted increased PTSD and depression symptom severity ...


Sars-Cov-2 Pandemic Analytical Overview With Machine Learning Predictability, Anthony Tanaydin, Jingchen Liang, Daniel W. Engels Jan 2021

Sars-Cov-2 Pandemic Analytical Overview With Machine Learning Predictability, Anthony Tanaydin, Jingchen Liang, Daniel W. Engels

SMU Data Science Review

Understanding diagnostic tests and examining important features of novel coronavirus (COVID-19) infection are essential steps for controlling the current pandemic of 2020. In this paper, we study the relationship between clinical diagnosis and analytical features of patient blood panels from the US, Mexico, and Brazil. Our analysis confirms that among adults, the risk of severe illness from COVID-19 increases with pre-existing conditions such as diabetes and immunosuppression. Although more than eight months into pandemic, more data have become available to indicate that more young adults were getting infected. In addition, we expand on the definition of COVID-19 test and discuss ...


The Zoltar Forecast Archive, A Tool To Standardize And Store Interdisciplinary Prediction Research, Nicholas G. Reich, Matthew Cornell, Evan L. Ray, Katie House, Khoa Le Jan 2021

The Zoltar Forecast Archive, A Tool To Standardize And Store Interdisciplinary Prediction Research, Nicholas G. Reich, Matthew Cornell, Evan L. Ray, Katie House, Khoa Le

Biostatistics and Epidemiology Faculty Publications Series

Forecasting has emerged as an important component of informed, data-driven decision-making in a wide array of felds. We introduce a new data model for probabilistic predictions that encompasses a wide range of forecasting settings. This framework clearly defnes the constituent parts of a probabilistic forecast and proposes one approach for representing these data elements. The data model is implemented in Zoltar, a new software application that stores forecasts using the data model and provides standardized API access to the data. In one real-time case study, an instance of the Zoltar web application was used to store, provide access to, and ...


Principal Components Analysis Corrects Collider Bias In Polygenic Risk Score Effect Size Estimation, Nathaniel S. Thomas, Peter B. Barr, Fazil Aliev, Sally I. Kuo, Danielle M. Dick, Jessica E. Salvatore Jan 2021

Principal Components Analysis Corrects Collider Bias In Polygenic Risk Score Effect Size Estimation, Nathaniel S. Thomas, Peter B. Barr, Fazil Aliev, Sally I. Kuo, Danielle M. Dick, Jessica E. Salvatore

Graduate Research Posters

BACKGROUND: Genome-wide polygenic scoring has emerged as a way to predict psychiatric and behavioral outcomes and identify environments that promote the expression of genetic risks. An increasing number of studies demonstrate that the effects of polygenic risk scores (PRS) may be biased by the inclusion of heritable environments as covariates when the environment is influenced by unmeasured confounding variables, an example of collider bias. Inclusion of the principal components of observed confounders as covariates may correct for the effect of unmeasured confounders.

METHODS: A simulation study was conducted to test principal components analysis (PCA) as a correction for collider bias ...


Methods For Developing A Machine Learning Framework For Precise 3d Domain Boundary Prediction At Base-Level Resolution, Spiro C. Stilianoudakis Jan 2021

Methods For Developing A Machine Learning Framework For Precise 3d Domain Boundary Prediction At Base-Level Resolution, Spiro C. Stilianoudakis

Theses and Dissertations

High-throughput chromosome conformation capture technology (Hi-C) has revealed extensive DNA looping and folding into discrete 3D domains. These include Topologically Associating Domains (TADs) and chromatin loops, the 3D domains critical for cellular processes like gene regulation and cell differentiation. The relatively low resolution of Hi-C data (regions of several kilobases in size) prevents precise mapping of domain boundaries by conventional TAD/loop-callers. However, high resolution genomic annotations associated with boundaries, such as CTCF and members of cohesin complex, suggest a computational approach for precise location of domain boundaries.

We developed preciseTAD, an optimized machine learning framework that leverages a random ...


A Bayesian Hierarchical Mixture Model With Continuous-Time Markov Chains To Capture Bumblebee Foraging Behavior, Max Thrush Hukill Jan 2021

A Bayesian Hierarchical Mixture Model With Continuous-Time Markov Chains To Capture Bumblebee Foraging Behavior, Max Thrush Hukill

Honors Projects

The standard statistical methodology for analyzing complex case-control studies in ethology is often limited by approaches that force researchers to model distinct aspects of biological processes in a piecemeal, disjointed fashion. By developing a hierarchical Bayesian model, this work demonstrates that statistical inference in this context can be done using a single coherent framework. To do this, we construct a continuous-time Markov chain (CTMC) to model bumblebee foraging behavior. To connect the experimental design with the CTMC, we employ a mixture model controlled by a logistic regression on the two-factor design matrix. We then show how to infer these model ...


Piecewise Linear Regression For Leaf Appearance Rate Data, Lin Quan Jan 2021

Piecewise Linear Regression For Leaf Appearance Rate Data, Lin Quan

Creative Components

Segmented regression models are generalization of linear and generalized linear models that replace a linear predictor with a piecewise linear predictor. Breakpoints where the piecewise linear predictor changes slope are unknown and estimated from data. We use segmented regression to model the relationship between the number of plant leaves and thermal time for hundreds of maize genotypes. Slope estimates from fitted segmented regression models provide estimates of leaf appearance rate (LAR) for each genotype. Estimates of breakpoints provide insight into developmental time points when changes in LAR occur for each genotype. We compare inferences about slopes and breakpoints obtained from ...


An Updated Method For Correcting Batch Effect, Yonghui Huo Jan 2021

An Updated Method For Correcting Batch Effect, Yonghui Huo

Creative Components

Abstract

I propose a novel variation (Pro-SVA) on iteratively reweighted surrogate variable analysis (IRW-SVA) for detecting and measuring batch effects in high dimensional gene expression data. Specifically, I propose to use the matrix-free high dimensional factor analysis (HDFA) algorithm instead of singular value decomposition (SVD) in the IRW-SVA iterations. HDFA efficiently provides the maximum likelihood estimates of the error variances and batch loadings, which can subsequently be used to estimate the batch factors. To evaluate the performance of Pro-SVA, I simulated 100 samples of 1,000 genes with batch effects and (1) no biological effects, (2) biological effects for half ...


A Model For Inhalation Of Infectious Aerosol Contaminants In An Aircraft Passenger Cabin, Bert A. Silich Jan 2021

A Model For Inhalation Of Infectious Aerosol Contaminants In An Aircraft Passenger Cabin, Bert A. Silich

International Journal of Aviation, Aeronautics, and Aerospace

Aerosol contamination of an aircraft cabin by infectious passengers is a concern of passengers, aircrew and the aviation industry. This may be especially important during a pandemic, such as COVID-19, where the full extent of aerosol transmission is not well understood. A statistical method to determine the number of infectious passengers on board along with a mathematical model estimating the contaminant concentration of aerosols in the cabin and the number of inhaled infectious particles by passengers is presented. An example is used to demonstrated how the results can be estimated during normal operations and emergency conditions with malfunctions of the ...


The Causes And Control Measures Of Extended Spectrum Beta-Lactamase Producing Enterobacteriaceae In Long-Term Care Facilities, Ismaila Olatunji Sule Jan 2021

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 ...


Dach1 Mutation Frequency In Endometrial Cancer Is Associated With High Tumor Mutation Burden, Mckayla J. Riggs, Nan Lin, Chi Wang, Dava W. Piecoro, Rachel W. Miller, Oliver A. Hampton, Mahadev Rao, Frederick R. Ueland, Jill M. Kolesar Dec 2020

Dach1 Mutation Frequency In Endometrial Cancer Is Associated With High Tumor Mutation Burden, Mckayla J. Riggs, Nan Lin, Chi Wang, Dava W. Piecoro, Rachel W. Miller, Oliver A. Hampton, Mahadev Rao, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: DACH1 is a transcriptional repressor and tumor suppressor gene frequently mutated in melanoma, bladder, and prostate cancer. Loss of DACH1 expression is associated with poor prognostic features and reduced overall survival in uterine cancer. In this study, we utilized the Oncology Research Information Exchange Network (ORIEN) Avatar database to determine the frequency of DACH1 mutations in patients with endometrial cancer in our Kentucky population.

METHODS: We obtained clinical and genomic data for 65 patients with endometrial cancer from the Markey Cancer Center (MCC). We examined the clinical attributes of the cancers by DACH1 status by comparing whole-exome sequencing (WES ...