Medicine and Health Sciences Commons^™

Long-Read Sequencing Of The Zebrafish Genome Reorganizes Genomic Architecture, Yelena Chernyavskaya, Xiaofei Zhang, Jinze Liu, Jessica Blackburn

Biostatistics Publications

Background

Nanopore sequencing technology has revolutionized the field of genome biology with its ability to generate extra-long reads that can resolve regions of the genome that were previously inaccessible to short-read sequencing platforms. Over 50% of the zebrafish genome consists of difficult to map, highly repetitive, low complexity elements that pose inherent problems for short-read sequencers and assemblers.

Results

We used long-read nanopore sequencing to generate a de novo assembly of the zebrafish genome and compared our assembly to the current reference genome, GRCz11. The new assembly identified 1697 novel insertions and deletions over one kilobase in length and placed …

Managing Hypertension, Diabetes, And Cardiovascular Disease Risk Via Short-Term Medical Trips: A Retrospective Longitudinal Study In Santo Domingo, Rose Baumann, Reuben P. Retnam, Carlos M. Hernandez, Victoria Edwards, Mark Ryan

Biostatistics Publications

Background: Short-term medical trips (STMTs) from high-resource countries frequently provide care in low and middle-income countries. Little existing literature objectively tracks the long-term outcomes of these interventions on the receiving populations over time to assess potential benefits and to ensure no harm is being done.

Objectives: The purpose of this study was to objectively analyze the outcomes of a biannual STMT to Santo Domingo, Dominican Republic on hypertension (HTN), diabetes mellitus type 2 (DM2), and cardiovascular disease (CVD) risk over a five-year period (2015-2019).

Methods: Data from 1655 patients was extracted from the electronic medical record. In …

Identifying Attrition Phases In Survey Data: Applicability And Assessment Study, Camille J. Hochheimer, Roy T. Sabo, Robert A. Perera, Nitai Mukhopadhyay, Alex H. Krist

Biostatistics Publications

Background: Although Web-based questionnaires are an efficient, increasingly popular mode of data collection, their utility is often challenged by high participant dropout. Researchers can gain insight into potential causes of high participant dropout by analyzing the dropout patterns.

Objective: This study proposed the application of and assessed the use of user-specified and existing hypothesis testing methods in a novel setting—survey dropout data—to identify phases of higher or lower survey dropout.

Methods: First, we proposed the application of user-specified thresholds to identify abrupt differences in the dropout rate. Second, we proposed the application of 2 existing hypothesis testing methods to detect …

Improving Temporal Accuracy Of Human Metabolic Chambers For Dynamic Metabolic Studies, Shanshan Chen, Erica Wohlers, Eric Ruud, Jon Moon, Bin Ni, Francesco S. Celi

Biostatistics Publications

Metabolic chambers are powerful tools for assessing human energy expenditure, providing flexibility and comfort for the subjects in a near free-living environment. However, the flexibility offered by the large living room size creates challenges in the assessment of dynamic human metabolic signals—such as those generated during high-intensity interval training and short-term involuntary physical activities—with sufficient temporal accuracy. Therefore, this paper presents methods to improve the temporal accuracy of metabolic chambers. The proposed methods include 1) adopting a shortest possible step size, here one minute, to compute the finite derivative terms for the metabolic rate calculation, and 2) applying a robust …

Comorbidity, Pain, Utilization, And Psychosocial Outcomes In Older Versus Younger Sickle Cell Adults: The Pisces Project, Donna K. Mcclish, Wally R. Smith, James L. Levenson, Imoigele P. Aisiku, John D. Roberts, Susan D. Roseff, Viktor E. Bovbjerg

Biostatistics Publications

Background. Patients with SCD now usually live well into adulthood. Whereas transitions into adulthood are now often studied, little is published about aging beyond the transition period. We therefore studied age-associated SCD differences in utilization, pain, and psychosocial variables. Methods. Subjects were 232 adults in the Pain in Sickle Cell Epidemiology Study (PiSCES). Data included demographics, comorbidity, and psychosocial measures. SCD-related pain and health care utilization were recorded in diaries. We compared 3 age groups: 16–25 (transition), 26–36 (younger adults), and 37–64 (older adults) years. Results. Compared to the 2 adult groups, the transition group reported fewer …

Quantifying Variation In Gait Features From Wearable Inertial Sensors Using Mixed Effects Models, Kellen Garrison Cresswell, Yongyun Shin, Shanshan Chen

Biostatistics Publications

The emerging technology of wearable inertial sensors has shown its advantages in collecting continuous longitudinal gait data outside laboratories. This freedom also presents challenges in collecting high-fidelity gait data. In the free-living environment, without constant supervision from researchers, sensor-based gait features are susceptible to variation from confounding factors such as gait speed and mounting uncertainty, which are challenging to control or estimate. This paper is one of the first attempts in the field to tackle such challenges using statistical modeling. By accepting the uncertainties and variation associated with wearable sensor-based gait data, we shift our efforts from detecting and correcting …

Saudi Scd Patients’ Symptoms And Quality Of Life Relative To The Number Of Ed Visits, Anwar E. Ahmed, Ahmed S. Alaskar, Donna K. Mcclish, Yosra Z. Ali, Mohammed H. Aldughither, Ahmad M. Al-Suliman, Hafiz M. Malhan

Biostatistics Publications

Background

Individuals living with sickle cell disease (SCD) have significantly increased emergency department (ED) use compared to the general population. In Saudi Arabia, health care is free for all individuals and therefore has no bearing on increased ED visits. However, little is known about the relationship between quality of life (QoL) and frequency of acute care utilization in this patient population.

Methods

A cross-sectional study was conducted on 366 patients with SCD who attended the outpatient department at King Fahad Hospital, Hofuf, Saudi Arabia. Data were collected through self-administered surveys, which included: demographics, SCD-related ED visits, clinical issues, and QoL …

Methods For Evaluating Respondent Attrition In Web-Based Surveys, Camille J. Hochheimer, Roy T. Sabo, Alex H. Krist, Teresa Day, John Cyrus, Steven H. Woolf

Biostatistics Publications

Background: Electronic surveys are convenient, cost effective, and increasingly popular tools for collecting information. While the online platform allows researchers to recruit and enroll more participants, there is an increased risk of participant dropout in Web-based research. Often, these dropout trends are simply reported, adjusted for, or ignored altogether.

Objective: To propose a conceptual framework that analyzes respondent attrition and demonstrates the utility of these methods with existing survey data.

Methods: First, we suggest visualization of attrition trends using bar charts and survival curves. Next, we propose a generalized linear mixed model (GLMM) to detect or confirm …

Proton Pump Inhibitors Are Associated With Increased Risk Of Development Of Chronic Kidney Disease, Pradeep Arora, Anu Gupta, Mojgan Golzy, Nilang Patel, Randolph L. Carter, Kabir Jalal, James W. Lohr

Biostatistics Publications

Background

Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death.

Methods

Two separate retrospective case–control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at …

Improving Sensitivity Of Linear Regression-Based Cell Type-Specific Differential Expression Deconvolution With Per-Gene Vs. Global Significance Threshold, Edmund R. Glass, Mikhail G. Dozmorov

Biostatistics Publications

Background

The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from blood samples suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. Combined with cell counts, heterogeneous gene expression may provide deeper insights into the gene expression differences on the cell type-specific level.

Published computational methods use linear regression to estimate cell type-specific differential expression, and a global cutoff to judge significance, such as False Discovery Rate (FDR). Yet, they do not consider many artifacts …

Evaluation Of The Performance Of Smoothing Functions In Generalized Additive Models For Spatial Variation In Disease, Umaporn Siangphoe, David C. Wheeler

Biostatistics Publications

Generalized additive models (GAMs) with bivariate smoothing functions have been applied to estimate spatial variation in risk for many types of cancers. Only a handful of studies have evaluated the performance of smoothing functions applied in GAMs with regard to different geographical areas of elevated risk and different risk levels. This study evaluates the ability of different smoothing functions to detect overall spatial variation of risk and elevated risk in diverse geographical areas at various risk levels using a simulation study. We created five scenarios with different true risk area shapes (circle, triangle, linear) in a square study region. We …

Assessment Of Residential History Generation Using A Public-Record Database, David C. Wheeler, Aobo Wang

Biostatistics Publications

In studies of disease with potential environmental risk factors, residential location is often used as a surrogate for unknown environmental exposures or as a basis for assigning environmental exposures. These studies most typically use the residential location at the time of diagnosis due to ease of collection. However, previous residential locations may be more useful for risk analysis because of population mobility and disease latency. When residential histories have not been collected in a study, it may be possible to generate them through public-record databases. In this study, we evaluated the ability of a public-records database from LexisNexis to provide …

Proceedings Of The 2015 Midsouth Computational Biology And Bioinformatics Society (Mcbios) Conference, Jonathan D. Wren, Shraddha Thakkar, Ramin Homayouni, Donald J. Johann, Mikhail G. Dozmorov

Biostatistics Publications

No abstract provided.

What Was Glaucoma Called Before The 20th Century?, Christopher T. Leffler, Stephen G. Schwartz, Francesca M. Giliberti, Matthew T. Young, Dennis Bermudez

Biostatistics Publications

Glaucoma involves a characteristic optic neuropathy, often with elevated intraocular pressure. Before 1850, poor vision with a normal eye appearance, as occurs in primary open-angle glaucoma, was termed amaurosis, gutta serena, or black cataract. Few observers noted palpable hardness of the eye in amaurosis. On the other hand, angle-closure glaucoma can produce a green or gray pupil, and therefore was called, variously, glaucoma (derived from the Greek for glaucous, a nonspecific term connoting blue, green, or light gray) and viriditate oculi. Angle closure, with palpable hardness of the eye, mydriasis, and anterior prominence of the lens, was described in greater …

Penalized Ordinal Regression Methods For Predicting Stage Of Cancer In High-Dimensional Covariate Spaces, Amanda Elswick Gentry, Colleen K. Jackson-Cook, Debra E. Lyon, Kellie J. Archer

Biostatistics Publications

The pathological description of the stage of a tumor is an important clinical designation and is considered, like many other forms of biomedical data, an ordinal outcome. Currently, statistical methods for predicting an ordinal outcome using clinical, demographic, and high-dimensional correlated features are lacking. In this paper, we propose a method that fits an ordinal response model to predict an ordinal outcome for high-dimensional covariate spaces. Our method penalizes some covariates (high-throughput genomic features) without penalizing others (such as demographic and/or clinical covariates). We demonstrate the application of our method to predict the stage of breast cancer. In our model, …

Assessment Of Weighted Quantile Sum Regression For Modeling Chemical Mixtures And Cancer Risk, Jenna Czarnota, Chris Gennings, David C. Wheeler

Biostatistics Publications

In evaluation of cancer risk related to environmental chemical exposures, the effect of many chemicals on disease is ultimately of interest. However, because of potentially strong correlations among chemicals that occur together, traditional regression methods suffer from collinearity effects, including regression coefficient sign reversal and variance inflation. In addition, penalized regression methods designed to remediate collinearity may have limitations in selecting the truly bad actors among many correlated components. The recently proposed method of weighted quantile sum (WQS) regression attempts to overcome these problems by estimating a body burden index, which identifies important chemicals in a mixture of correlated environmental …

Identifying Molecular Features Associated With Psychoneurological Symptoms In Women With Breast Cancer Using Multivariate Mixed Models, Qing Zhou, Colleen Jackson-Cook, Debra Lyon, Robert Perera, Kellie Archer

Biostatistics Publications

Breast cancer (BC) is the second most common cancer among women. Research shows many women with BC experience anxiety, depression, and stress (ADS). Epigenetics has recently emerged as a potential mechanism for the development of depression.1 Although there are growing numbers of research studies indicating that epigenetic changes are associated with ADS, there is currently no evidence that this association is present in women with BC. The goal of this study was to identify high-throughput methylation sites (CpG sites) that are associated with three psychoneurological symptoms (ADS) in women with BC. Traditionally, univariate models have been used to examine …

Computer Simulation, Bioinformatics, And Statistical Analysis Of Cancer Data And Processes, Kellie J. Archer, Kevin Dobbin, Swati Biswas, Roger S. Day, David C. Wheeler, Hao Wu

Biostatistics Publications

No abstract provided.

Health-Related Quality Of Life In Patients With Sickle Cell Disease In Saudi Arabia, Anwar E. Ahmed, Ahmed S. Alaskar, Ahmad M. Al-Suliman, Abdul-Rahman Jazieh, Donna K. Mcclish, Majid Al Salamah, Yosra Z. Ali, Hafiz Malhan, May Anne Mendoza, Abdulrahman O. Gorashi, Mohamed E. El-Toum, Wala E. El-Toum

Biostatistics Publications

Background

There is a lack of research concerning health-related quality of life (HRQoL) in Saudi patients with sickle cell disease (SCD), particularly among adult populations. The aim of the current study was to describe the characteristics of SCD patients and their impact on their quality of life (QoL).

Methods

Six hundred twenty-nine adult SCD patients who attended King Fahad Hospital in Hofuf and King Fahad Central Hospital in Jazan were included in the analysis. Demographic/clinical data were collected and an Arabic version of the Medical Outcomes 36-Item Short-Form Health Survey (SF-36) questionnaire was used to assess QoL.

Results

SCD patients …

Generalized Monotone Incremental Forward Stagewise Method For Modeling Count Data: Application Predicting Micronuclei Frequency, Mateusz Makowski, Kellie J. Archer

Biostatistics Publications

The cytokinesis-block micronucleus (CBMN) assay can be used to quantify micronucleus (MN) formation, the outcome measured being MN frequency. MN frequency has been shown to be both an accurate measure of chromosomal instability/DNA damage and a risk factor for cancer. Similarly, the Agilent 4×44k human oligonucleotide microarray can be used to quantify gene expression changes. Despite the existence of accepted methodologies to quantify both MN frequency and gene expression, very little is known about the association between the two. In modeling our count outcome (MN frequency) using gene expression levels from the high-throughput assay as our predictor variables, there are …

Assessment Of Residential History Generation Using A Public-Record Database, David C. Wheeler, Aobo Wang

Biostatistics Publications

In studies of disease with potential environmental risk factors, residential location is often used as a surrogate for unknown environmental exposures or as a basis for assigning environmental exposures. These studies most typically use the residential location at the time of diagnosis due to ease of collection. However, previous residential locations may be more useful for risk analysis because of population mobility and disease latency. When residential histories have not been collected in a study, it may be possible to generate them through public-record databases. In this study, we evaluated the ability of a public-records database from LexisNexis to provide …

Analysis Of Environmental Chemical Mixtures And Non-Hodgkin Lymphoma Risk In The Nci-Seer Nhl Study, Jenna Czarnota, Chris Gennings, Joanne S. Colt, Anneclaire J. De Roos, James R. Cerhan, Richard K. Severson, Patricia Hartge, Mary H. Ward, David C. Wheeler

Biostatistics Publications

Background: There are several suspected environmental risk factors for non-Hodgkin lymphoma (NHL). The associations between NHL and environmental chemical exposures have typically been evaluated for individual chemicals (i.e., one-by-one).

Objectives: We determined the association between a mixture of 27 correlated chemicals measured in house dust and NHL risk.

Methods: We conducted a population-based case–control study of NHL in four National Cancer Institute–Surveillance, Epidemiology, and End Results centers—Detroit, Michigan; Iowa; Los Angeles County, California; and Seattle, Washington—from 1998 to 2000. We used weighted quantile sum (WQS) regression to model the association of a mixture of chemicals and risk of NHL. The …

Pdgfrα Signaling Drives Adipose Tissue Fibrosis By Targeting Progenitor Cell Plasticity, Tomoaki Iwayama, Cameron Steele, Longbiao Yao, Mikhail G. Dozmorov, Dimitris Karamichos, Jonathan D. Wren, Lorin E. Olson

Biostatistics Publications

Fibrosis is a common disease process in which profibrotic cells disturb organ function by secreting disorganized extracellular matrix (ECM). Adipose tissue fibrosis occurs during obesity and is associated with metabolic dysfunction, but how profibrotic cells originate is still being elucidated. Here, we use a developmental model to investigate perivascular cells in white adipose tissue (WAT) and their potential to cause organ fibrosis. We show that a Nestin-Cre transgene targets perivascular cells (adventitial cells and pericyte-like cells) in WAT, and Nestin-GFP specifically labels pericyte-like cells. Activation of PDGFRα signaling in perivascular cells causes them to transition into ECM-synthesizing profibrotic cells. Before …

B-Cell And Monocyte Contribution To Systemic Lupus Erythematosus Identified By Cell-Type-Specific Differential Expression Analysis In Rna-Seq Data, Mikhail G. Dozmorov, Nicolas Dominguez, Krista Bean, Susan R. Macwana, Virginia Roberts, Edmund Glass, Judith A. James, Joel M. Guthridge

Biostatistics Publications

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by complex interplay among immune cell types. SLE activity is experimentally assessed by several blood tests, including gene expression profiling of heterogeneous populations of cells in peripheral blood. To better understand the contribution of different cell types in SLE pathogenesis, we applied the two methods in cell-type-specific differential expression analysis, csSAM and DSection, to identify cell-type-specific gene expression differences in heterogeneous gene expression measures obtained using RNA-seq technology. We identified B-cell-, monocyte-, and neutrophil-specific gene expression differences. Immunoglobulin-coding gene expression was altered in B-cells, while a ribosomal signature was prominent in …

Evaluating Geographically Weighted Regression Models For Environmental Chemical Risk Analysis, Jenna Czarnota, David C. Wheeler, Chris Gennings

Biostatistics Publications

In the evaluation of cancer risk related to environmental chemical exposures, the effect of many correlated chemicals on disease is often of interest. The relationship between correlated environmental chemicals and health effects is not always constant across a study area, as exposure levels may change spatially due to various environmental factors. Geographically weighted regression (GWR) has been proposed to model spatially varying effects. However, concerns about collinearity effects, including regression coefficient sign reversal (ie, reversal paradox), may limit the applicability of GWR for environmental chemical risk analysis. A penalized version of GWR, the geographically weighted lasso, has been proposed to …

Detrimental Effects Of Duplicate Reads And Low Complexity Regions On Rna- And Chip-Seq Data, Mikhail G. Dozmorov, Indra Adrianto, Cory B. Giles, Edmund Glass, Stuart B. Glenn, Courtney Montgomery, Kathy L. Sivils, Lorin E. Olson, Tomoaki Iwayama, Willard M. Freeman, Christopher J. Lessard, Jonathan D. Wren

Biostatistics Publications

Background

Adapter trimming and removal of duplicate reads are common practices in next-generation sequencing pipelines. Sequencing reads ambiguously mapped to repetitive and low complexity regions can also be problematic for accurate assessment of the biological signal, yet their impact on sequencing data has not received much attention. We investigate how trimming the adapters, removing duplicates, and filtering out reads overlapping low complexity regions influence the significance of biological signal in RNA- and ChIP-seq experiments.

Methods

We assessed the effect of data processing steps on the alignment statistics and the functional enrichment analysis results of RNA- and ChIP-seq data. We compared …

Detrimental Effects Of Duplicate Reads And Low Complexity Regions On Rna- And Chip-Seq Data, Mikhail G. Dozmorov, Indra Adrianto, Cory B. Giles, Edmud Glass, Stuart B. Glenn, Courtney Montgomery, Kathy L. Sivils, Lorin E. Olson, Tomoaki Iwayama, Willard M. Freeman, Christopher J. Lessard, Jonathan D. Wren

Biostatistics Publications

Background

Adapter trimming and removal of duplicate reads are common practices in next-generation sequencing pipelines. Sequencing reads ambiguously mapped to repetitive and low complexity regions can also be problematic for accurate assessment of the biological signal, yet their impact on sequencing data has not received much attention. We investigate how trimming the adapters, removing duplicates, and filtering out reads overlapping low complexity regions influence the significance of biological signal in RNA- and ChIP-seq experiments.

Methods

We assessed the effect of data processing steps on the alignment statistics and the functional enrichment analysis results of RNA- and ChIP-seq data. We compared …

Catchment Area Analysis Using Bayesian Regression Modeling, Aobo Wang, David C. Wheeler

Biostatistics Publications

A catchment area (CA) is the geographic area and population from which a cancer center draws patients. Defining a CA allows a cancer center to describe its primary patient population and assess how well it meets the needs of cancer patients within the CA. A CA definition is required for cancer centers applying for National Cancer Institute (NCI)-designated cancer center status. In this research, we constructed both diagnosis and diagnosis/treatment CAs for the Massey Cancer Center (MCC) at Virginia Commonwealth University. We constructed diagnosis CAs for all cancers based on Virginia state cancer registry data and Bayesian hierarchical logistic regression …

Dvt Surveillance Program In The Icu: Analysis Of Cost-Effectiveness, Ajai K. Malhotra, Stephanie R. Goldberg, Laura Mclay, Nancy R. Martin, Luke G. Wolfe, Mark M. Levy, Vishal Khiatani, Todd C. Borchers, Therese M. Duane, Michel B. Aboutanos, Rao R. Ivatury

Biostatistics Publications

Background

Venous Thrombo-embolism (VTE – Deep venous thrombosis (DVT) and/or pulmonary embolism (PE) – in traumatized patients causes significant morbidity and mortality. The current study evaluates the effectiveness of DVT surveillance in reducing PE, and performs a cost-effectiveness analysis.

Methods

All traumatized patients admitted to the adult ICU underwent twice weekly DVT surveillance by bilateral lower extremity venous Duplex examination (48-month surveillance period – SP). The rates of DVT and PE were recorded and compared to the rates observed in the 36-month pre-surveillance period (PSP). All patients in both periods received mechanical and pharmacologic prophylaxis unless contraindicated. Total costs – …

A New Powerful Nonparametric Rank Test For Ordered Alternative Problem, Guogen Shan, Daniel Young, Le Kang

Biostatistics Publications

We propose a new nonparametric test for ordered alternative problem based on the rank difference between two observations from different groups. These groups are assumed to be independent from each other. The exact mean and variance of the test statistic under the null distribution are derived, and its asymptotic distribution is proven to be normal. Furthermore, an extensive power comparison between the new test and other commonly used tests shows that the new test is generally more powerful than others under various conditions, including the same type of distribution, and mixed distributions. A real example from an anti-hypertensive drug trial …