Statistics and Probability Commons^™

Assessing The Impact Of Differential Genotyping Errors On Rare Variant Tests Of Association, Morgan Mayer-Jochimsen, Shannon Fast, Nathan L. Tintle

Faculty Work Comprehensive List

Genotyping errors are well-known to impact the power and type I error rate in single marker tests of association. Genotyping errors that happen according to the same process in cases and controls are known as non-differential genotyping errors, whereas genotyping errors that occur with different processes in the cases and controls are known as differential genotype errors. For single marker tests, non-differential genotyping errors reduce power, while differential genotyping errors increase the type I error rate. However, little is known about the behavior of the new generation of rare variant tests of association in the presence of genotyping errors. In …

Progress Realized: Trends In Hiv-1 Viral Load And Cd4 Cell Count In A Tertiary-Care Center From 1999 Through 2011, Howard B. Gale, Manuel D. Rodriguez, Heather J. Hoffman, Debra A. Benator, Fred M. Gordin, Ann M. Labriola, Virginia L. Kan

Epidemiology Faculty Publications

Abstract

Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kB pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (PSNP-trend) for the association …

Gulf-Wide Decreases In The Size Of Large Coastal Sharks Documented By Generations Of Fishermen, Sean P. Powers, F. Joel Frodrie, Steven B. Scyphers, J. Marcus Drymon, Robert L. Shipp, Gregory W. Stunz

University Faculty and Staff Publications

Large sharks are top predators in most coastal and marine ecosystems throughout the world, and evidence of their reduced prominence in marine ecosystems has been a serious concern for fisheries and ecosystem management. Unfortunately, quantitative data to document the extent, timing, and consequences of changes in shark populations are scarce, thwarting examination of long-term (decadal, century) trends, and reconstructions based on incomplete data sets have been the subject of debate. Absence of quantitative descriptors of past ecological conditions is a generic problem facing many fields of science but is particularly troublesome for fisheries scientists who must develop specific targets for …

Multiscale Analysis Of Factors That Affect The Distribution Of Sharks Throughout The Northern Gulf Of Mexico, J. Marcus Drymon, Laure Carassou, Sean P. Powers, Mark Grace, John Dindo, Brian Dzwonkowski

University Faculty and Staff Publications

Identification of the spatial scale at which marine communities are organized is critical to proper management, yet this is particularly difficult to determine for highly migratory species like sharks. We used shark catch data collected during 2006–09 from fishery- independent bottom-longline surveys, as well as biotic and abiotic explanatory data to identify the factors that affect the distribution of coastal sharks at 2 spatial scales in the northern Gulf of Mexico. Centered principal component analyses (PCAs) were used to visualize the patterns that characterize shark distributions at small (Alabama and Mississippi coast) and large (northern Gulf of Mexico) spatial scales. …

Food For Thought … Mechanistic Validation, Thomas Hartung, Sebastian Hoffman, Martin Stephens

Experimentation Collection

Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st …

Next-Peak: A Normal-Exponential Two-Peak Model For Peak-Calling In Chip-Seq Data, Nak-Kyeong Kim, Rasika V. Jayatillake, John L. Spouge

Mathematics & Statistics Faculty Publications

Background: Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) can locate transcription factor binding sites on genomic scale. Although many models and programs are available to call peaks, none has dominated its competition in comparison studies.

Results: We propose a rigorous statistical model, the normal-exponential two-peak (NEXT-peak) model, which parallels the physical processes generating the empirical data, and which can naturally incorporate mappability information. The model therefore estimates total strength of binding (even if some binding locations do not map uniquely into a reference genome, effectively censoring them); it also assigns an error to an estimated binding location. The comparison study …

Spectral Cross Correlation As A Supervised Approach For The Analysis Of Complex Raman Datasets: The Case Of Nanoparticles In Biological Cells, Mark Keating, Franck Bonnier, Hugh Byrne

Articles

Spectral Cross-correlation is introduced as a methodology to identify the presence and subcellular distribution of nanoparticles in cells. Raman microscopy is employed to spectroscopically image biological cells previously exposed to polystyrene nanoparticles, as a model for the study of nano-bio interactions. The limitations of previously deployed strategies of K-means clustering analysis and principal component analysis are discussed and a novel methodology of Spectral Cross Correlation Analysis is introduced and compared with the performance of Classical Least Squares Analysis, in both unsupervised and supervised modes. The previous study demonstrated the feasibility of using Raman spectroscopy to map cells and identify polystyrene …

A Study Of Cellular Calcium Dynamics In Culture Using Fluorescence Microscopy – A Statistical And Mathematical Approach, Richard Adekola Idowu

Doctoral Dissertations

Calcium in its ionic form is very dynamic, especially in excitable cells such as muscle and brain cells, moving from the high concentration exterior of the cell to much lower concentrations inside the cell, where calcium is used as a second messenger. In brain cells, and neurons especially, calcium is a key signaling ion involved in memory and learning with excitatory neurotransmitters such as glutamate turning neurons "on." Glutamate excites the neurons in part by causing large and dynamic changes in the intracellular calcium concentration. While these dynamics are essential for normal signaling in the brain, excessive and sustained elevations …

Pastoral Lease Assessment Using Geospatial Analysis, T P. Robinson, P E. Novelly, R Corner, Philip Thomas, A Russell-Browm

Resource management technical reports

Seven remote sensing based Vegetation Indices (NDSVI, STVI-3, NDVI, Green + Red, Red, Land Monitor and STVI-1) were tested for their potential to discriminate between “poor” and “good” range condition assessments in Western Australia’s pastoral rangelands. Indices were computed using the Australian Greenhouse Office National Carbon Accounting System (AGO NCAS) repository of calibrated Landsat TM/ETM+ mosaics. Discrimination potential was assessed at two levels of stratification – station level (identical to the stratification used to collect the traverse data), and functional group level (an aggregation of similar land systems);

Genetic Susceptibility To Type 2 Diabetes: A Global Meta-Analysis Studying The Genetic Differences In Tunisian Populations, Rym Berhouma, S. Kouidhi, M. Ammar, H. Abid, T. Baroudi, H. Ennafaa, A. Benammar-Elgaaied

Human Biology Open Access Pre-Prints

The present study is the first meta-analysis to evaluate type 2 diabetes (T2D) - associated polymorphisms in cohorts originated from several Tunisian regions. In fact, we evaluated the effect of seven polymorphisms in the following genes; PPARg ( Pro12Ala), TNFα (-308A/G), ENPP1(K121Q), TCF7L2(rs7903146 C/T), MTHFR( C677T), ACE(I/D), CAPN10(3R/2R) on T2D risk, through a meta-analysis combining data of previous studies performed on Tunisian populations originating from the north, centre or south of the country. R statistics version 2.12.1 software was used to estimate the heterogeneity between studies. Pooled ORs were computed by the fixed-effects method of Mantel-Haenszel if no heterogeneity between …

Modeling And Mathematical Analysis Of Plant Models In Ecology, Eric A. Eager

Department of Mathematics: Dissertations, Theses, and Student Research

Population dynamics tries to explain in a simple mechanistic way the variations of the size and structure of biological populations. In this dissertation we use mathematical modeling and analysis to study the various aspects of the dynamics of plant populations and their seed banks.

In Chapter 2 we investigate the impact of structural model uncertainty by considering different nonlinear recruitment functions in an integral projection model for Cirsium canescens. We show that, while having identical equilibrium populations, these two models can elicit drastically different transient dynamics. We then derive a formula for the sensitivity of the equilibrium population to …

Assessing Movement Of Fish Through Spectral Analysis Of Otolith Life History Scans, Renee Reilly Hoover

OES Theses and Dissertations

The ability to accurately measure movement timing across environmental gradients is fundamental for testing hypotheses in marine ecology that deal with ingress, egress, and migration of fish. Timing and patterns of movement have been estimated using life-history scans of the chemical signatures encoded in fish otoliths (ear stones). I provide a quantitative approach to examining life history scan data using spectral analysis, which retrospectively measures the movement timing for individual fish. Sagittal otoliths from juvenile Atlantic croaker (Micropogonias undulates) and adult black sea bass (Centropristis striata) were sampled using laser ablation inductively coupled plasma mass spectrometry …

A Statistical Model To Determine Multiple Binding Sites Of A Transcription Factor On Dna Using Chip-Seq Data, Rasika Jayatillake

Mathematics & Statistics Theses & Dissertations

Protein-DNA interaction is vital to many biological processes in cells such as cell division, embryo development and regulating gene expression. Chromatin Immunoprecipitation followed by massively parallel sequencing (ChIP-seq) is a new technology that can reveal protein binding sites in genome with superior accuracy. Although many methods have been proposed to find binding sites for ChIP-seq data, they can find only one binding site within a short region of the genome. In this study we introduce a statistical model to identify multiple binding sites of a transcription factor within a short region of the genome using the ChIP-seq data. Mapped sequence …

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.

Why Odds Ratio Estimates Of Gwas Are Almost Always Close To 1.0, Yutaka Yasui

COBRA Preprint Series

“Missing heritability” in genome-wide association studies (GWAS) refers to the seeming inability for GWAS data to capture the great majority of genetic causes of a disease in comparison to the known degree of heritability for the disease, in spite of GWAS’ genome-wide measures of genetic variations. This paper presents a simple mathematical explanation for this phenomenon, assuming that the heritability information exists in GWAS data. Specifically, it focuses on the fact that the great majority of association measures (in the form of odds ratios) from GWAS are consistently close to the value that indicates no association, explains why this occurs, …

The Efficacy Of An Audio Program And Discussion Guide In Promoting Exclusive Breastfeeding In Cameroon, Africa, Kathryn R. Reinsma

Loma Linda University Electronic Theses, Dissertations & Projects

Background: In the Northwest Region of Cameroon, approximately 90% of women initiate breastfeeding; however, only 34% continue exclusive breastfeeding for the recommended six months (Kakute, et al., 2005; WHO, 2008). Entertainment-education is a mass-media communication strategy of placing educational information into media such as television programs, movies, and radio programs (Siegel & Lotenberg, 2007). This form of behavioral change communication has proven effective in addressing health-related issues in developing countries.

Purpose: The aim was to design an audio program and discussion guide to test the hypothesis that an audio program and discussion guide improves exclusive breastfeeding knowledge, beliefs, benefits, self-efficacy, …

Generalized Linear Latent Mixed Modeling Of Functional Independent Measures And Patient Outcomes, Maduranga Kasun Dassanayake

Open Access Theses & Dissertations

The Functional Independent Measure (FIM) is one of the most widely accepted functional assessment measures used in the rehabilitation community. Past research studies have investigated the relationship between place of discharge, admission FIM scores or FIM difference scores, and patients' characteristics and found relationships between those variables. However, most of these studies fail to account for the multi-layered multidimensionality of the FIM and the measurement error associated with the FIM items. This study utilizes Generalized Linear Latent Mixed Models (GLLAMM) and Structural Equation Models (SEM) to assess which patient characteristics are associated with FIM difference scores and the structural relationship …

Grts And Graphs: Monitoring Natural Resources In Urban Landscapes, Todd R. Lookingbill, John Paul Schmit, Shawn L. Carter

Geography and the Environment Faculty Publications

Environmental monitoring programs are an important tool for providing land managers with a scientific basis for management decisions. However, many ecological processes operate on spatial scales that transcend management boundaries (Schonewald-Cox 1988). For example, adjacent lands may influence protected-area resources via edge effects, source-sink dynamics, or invasion processes (Jones et al. 2009). Hydrologic alterations outside management units also may have profound effects on the integrity of resources being managed (Pringle 2000). The impacts of climate change are presenting challenges to resource management at local-to-global scales (Karl et al. 2009). This potential disparity between ecological and political boundaries presents an interesting …

Association Between Chemical Constituents Of Particulate Matter And Cardiovascular And Respiratory Morbidities In Nys, Rena Jones

Legacy Theses & Dissertations (2009 - 2024)

Improved understanding of health risks from short- and long-term exposure to fine particulate matter (PM_2.5) constituents may explain seasonal and geographic heterogeneity in PM_{2.5-health associations and inform control efforts targeting PM sources. Few studies have examined PM species health effects; most have been limited by their exposure assessments and modeling approaches. The goals of this project were to improve the PM exposure assessment and explore relationships between PM2.5 species and health in acute and chronic contexts.}

Probability Of Identification: A Statistical Model For The Validation Of Qualitative Botanical Identification Methods, Robert A. Labudde, James M. Harnly

Mathematics & Statistics Faculty Publications

A qualitative botanical identification method (BIM) is an analytical procedure that returns a binary result (1 = Identified, 0 = Not Identified). A BIM may be used by a buyer, manufacturer, or regulator to determine whether a botanical material being tested is the same as the target (desired) material, or whether it contains excessive nontarget (undesirable) material. The report describes the development and validation of studies for a BIM based on the proportion of replicates identified, or probability of identification (POI), as the basic observed statistic. The statistical procedures proposed for data analysis follow closely those of the probability of …

Secondary Structure Prediction Of Long Rna Sequences Based On Inversion Excursions And A Modularized Mapreduce Framework, Daniel Tesfai Yehdego

Open Access Theses & Dissertations

Ribonucleic acid (RNA) molecules and their secondary structures play important roles in many biological processes including gene expression and regulation. The genomes of many viruses are also RNA molecules. Since secondary structures are crucial for RNA functionality, computational predictions of the RNA secondary structures have been widely studied. However, the tremendous demands on computer memory and computing time for complex secondary structures limit the capability of existing thermodynamically based algorithms for structure predictions to handling only short RNA sequences with a few hundred bases. One approach to overcome this limitation is by first cutting long RNA sequences into shorter, non-overlapping …

Assessing The Impact Of Non-Differential Genotyping Errors On Rare Variant Tests Of Association, Scott Powers, Shyam Gopalakrishnan, Nathan L. Tintle

Faculty Work Comprehensive List

Background/Aims: We aim to quantify the effect of non-differential genotyping errors on the power of rare variant tests and identify those situations when genotyping errors are most harmful. Methods: We simulated genotype and phenotype data for a range of sample sizes, minor allele frequencies, disease relative risks and numbers of rare variants. Genotype errors were then simulated using five different error models covering a wide range of error rates. Results: Even at very low error rates, misclassifying a common homozygote as a heterozygote translates into a substantial loss of power, a result that is exacerbated even further as the minor …

Habitat Use And Abundance Patterns Of Sandhill Cranes In The Central Platte River Valley, Nebraska, 2003–2010, Todd Joseph Buckley

School of Natural Resources: Dissertations, Theses, and Student Research

The Central Platte River Valley (CPRV) in Nebraska is an important spring stopover area for the midcontinent population of sandhill cranes. Alterations to crop rotation and loss habitat in the CPRV pose a risk to the population. Personnel drove designated routes in the CPRV from 2003–2010 to record the presence of cranes in agricultural fields and estimate abundance. I developed and evaluated models to predict habitat use and flock sizes. Alfalfa was predicted to receive the highest use followed by corn, soybeans, winter wheat, grassland, and shrubland. Use of all habitats and flock size increased as field area increased. Flock …

Estimation Of A Non-Parametric Variable Importance Measure Of A Continuous Exposure, Chambaz Antoine, Pierre Neuvial, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We define a new measure of variable importance of an exposure on a continuous outcome, accounting for potential confounders. The exposure features a reference level x0 with positive mass and a continuum of other levels. For the purpose of estimating it, we fully develop the semi-parametric estimation methodology called targeted minimum loss estimation methodology (TMLE) [van der Laan & Rubin, 2006; van der Laan & Rose, 2011]. We cover the whole spectrum of its theoretical study (convergence of the iterative procedure which is at the core of the TMLE methodology; consistency and asymptotic normality of the estimator), practical implementation, simulation …

Multiple Testing Of Local Maxima For Detection Of Peaks In Chip-Seq Data, Armin Schwartzman, Andrew Jaffe, Yulia Gavrilov, Clifford A. Meyer

Harvard University Biostatistics Working Paper Series

No abstract provided.

Gene By Bmi Interactions Influencing C-Reactive Protein Levels In European-Americans, Sarah Tudor

Dissertations and Theses (Open Access)

C-Reactive Protein (CRP) is a biomarker indicating tissue damage, inflammation, and infection. High-sensitivity CRP (hsCRP) is an emerging biomarker often used to estimate an individual’s risk for future coronary heart disease (CHD). hsCRP levels falling below 1.00 mg/l indicate a low risk for developing CHD, levels ranging between 1.00 mg/l and 3.00 mg/l indicate an elevated risk, and levels exceeding 3.00 mg/l indicate high risk. Multiple Genome-Wide Association Studies (GWAS) have identified a number of genetic polymorphisms which influence CRP levels. SNPs implicated in such studies have been found in or near genes of interest including: CRP, APOE, APOC, IL-6, …

Heterogeneity, Control, Social Infrastructure, And Possibilities Of Participation: Their Interplay In Modern Understandings Of Heredity And In Interpretation Of Science, Peter J. Taylor

Working Papers on Science in a Changing World

This working paper is a prospectus for research, writing, and engagement. It consists of vignettes, sketches of lines of inquiry, and proposals for engagement, all of which concern modern understandings of heredity and development over the life course as well as the social interpretation of science. The various items address a range of areas of science and of its interpretation: heritability studies, the social uses of genetic information, gene-by-environment interaction, personalized medicine, IQ paradoxes, racial group membership, biobanks, and life events and difficulties research. Fresh perspectives in these areas are opened up by examining the ways that research and application …

A Unified Approach To Non-Negative Matrix Factorization And Probabilistic Latent Semantic Indexing, Karthik Devarajan, Guoli Wang, Nader Ebrahimi

COBRA Preprint Series

Non-negative matrix factorization (NMF) by the multiplicative updates algorithm is a powerful machine learning method for decomposing a high-dimensional nonnegative matrix V into two matrices, W and H, each with nonnegative entries, V ~ WH. NMF has been shown to have a unique parts-based, sparse representation of the data. The nonnegativity constraints in NMF allow only additive combinations of the data which enables it to learn parts that have distinct physical representations in reality. In the last few years, NMF has been successfully applied in a variety of areas such as natural language processing, information retrieval, image processing, speech recognition …

A Study On Facility Planning Using Discrete Event Simulation: Case Study Of A Grain Delivery Terminal, Sarah M. Asio

Department of Industrial and Management Systems Engineering: Dissertations, Theses, and Student Research

The application of traditional approaches to the design of efficient facilities can be tedious and time consuming when uncertainty and a number of constraints exist. Queuing models and mathematical programming techniques are not able to capture the complex interaction between resources, the environment and space constraints for dynamic stochastic processes. In the following study discrete event simulation is applied to the facility planning process for a grain delivery terminal. The discrete event simulation approach has been applied to studies such as capacity planning and facility layout for a gasoline station and evaluating the resource requirements for a manufacturing facility. To …

A Bayesian Model Averaging Approach For Observational Gene Expression Studies, Xi Kathy Zhou, Fei Liu, Andrew J. Dannenberg

COBRA Preprint Series

Identifying differentially expressed (DE) genes associated with a sample characteristic is the primary objective of many microarray studies. As more and more studies are carried out with observational rather than well controlled experimental samples, it becomes important to evaluate and properly control the impact of sample heterogeneity on DE gene finding. Typical methods for identifying DE genes require ranking all the genes according to a pre-selected statistic based on a single model for two or more group comparisons, with or without adjustment for other covariates. Such single model approaches unavoidably result in model misspecification, which can lead to increased error …