Medical Biomathematics and Biometrics Commons^™

Quantification Of Piscine Reovirus (Prv) At Different Stages Of Atlantic Salmon Salmo Salar Production, Torstein Tengs Dr.

Dr. Torstein Tengs

The newly described piscine reovirus (PRV) appears to be associated with the development of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon Salmo salar L. PRV seems to be ubiquitous among fish in Norwegian salmon farms, but high viral loads and tissue distribution support a causal relationship between virus and disease. In order to improve understanding of the distribution of PRV in the salmon production line, we quantified PRV by using real-time PCR on heart samples collected at different points in the life cycle from pre-smolts to fish ready for slaughter. PRV positive pre-smolts were found in about …

Smoothness Selection For Penalized Quantile Regression Splines, Philip T. Reiss, Lei Huang

Philip T. Reiss

Modern data-rich analyses may call for fitting a large number of nonparametric quantile regressions. For example, growth charts may be constructed for each of a collection of variables, to identify those for which individuals with a disorder tend to fall in the tails of their age-specific distribution; such variables might serve as developmental biomarkers. When such analyses are carried out by penalized spline smoothing, reliable automatic selection of the smoothing parameter is particularly important. We show that two popular methods for smoothness selection may tend to overfit when estimating extreme quantiles as a smooth function of a predictor such as …

Semiparametric Methods For Mapping Brain Development, Philip T. Reiss, Yin-Hsiu Chen, Lan Huo

Philip T. Reiss

No abstract provided.

Characterization Of Gene–Environment Interactions For Colorectal Cancer Susceptibility Loci

Shuo Jiao

Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case–control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 …

Powerful Cocktail Methods For Detecting Genome-Wide Gene-Environment Interaction, Li Hsu, Shuo Jiao, James Y. Dai, Carolyn M. Hutter, Ulrike Peters, Charles Kooperberg

Shuo Jiao

Identifying gene and environment interaction (G × E) can provide insights into biological networks of complex diseases, identify novel genes that act synergistically with environmental factors, and inform risk prediction. However, despite the fact that hundreds of novel disease-associated loci have been identified from genome-wide association studies (GWAS), few G×Es have been discovered. One reason is thatmost studies are underpowered for detecting these interactions. Several new methods have been proposed to improve power for G × E analysis, but performance varies with scenario. In this article, we present a module-based approach to integrating various methods that exploits each method’s most …

Statistical Methods For Proteomic Biomarker Discovery Based On Feature Extraction Or Functional Modeling Approaches, Jeffrey S. Morris

Jeffrey S. Morris

In recent years, developments in molecular biotechnology have led to the increased promise of detecting and validating biomarkers, or molecular markers that relate to various biological or medical outcomes. Proteomics, the direct study of proteins in biological samples, plays an important role in the biomarker discovery process. These technologies produce complex, high dimensional functional and image data that present many analytical challenges that must be addressed properly for effective comparative proteomics studies that can yield potential biomarkers. Specific challenges include experimental design, preprocessing, feature extraction, and statistical analysis accounting for the inherent multiple testing issues. This paper reviews various computational …

Integrative Bayesian Analysis Of High-Dimensional Multi-Platform Genomics Data, Wenting Wang, Veerabhadran Baladandayuthapani, Jeffrey S. Morris, Bradley M. Broom, Ganiraju C. Manyam, Kim-Anh Do

Jeffrey S. Morris

Motivation: Analyzing data from multi-platform genomics experiments combined with patients’ clinical outcomes helps us understand the complex biological processes that characterize a disease, as well as how these processes relate to the development of the disease. Current integration approaches that treat the data are limited in that they do not consider the fundamental biological relationships that exist among the data from platforms.

Statistical Model: We propose an integrative Bayesian analysis of genomics data (iBAG) framework for identifying important genes/biomarkers that are associated with clinical outcome. This framework uses a hierarchical modeling technique to combine the data obtained from multiple platforms …

A Systematic Mapping Approach Of 16q12.2/Fto And Bmi In More Than 20,000 African Americans Narrows In On The Underlying Functional Variation: Results From The Population Architecture Using Genomics And Epidemiology (Page) Study

Shuo Jiao

Genetic variants in intron 1 of the fat mass– and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI–associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped …

Genome-Wide Search For Gene-Gene Interactions In Colorectal Cancer

Shuo Jiao

Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to …

James-Stein Estimation And The Benjamini-Hochberg Procedure, Debashis Ghosh

Debashis Ghosh

For the problem of multiple testing, the Benjamini-Hochberg (B-H) procedure has become a very popular method in applications. Based on a spacings theory representation of the B-H procedure, we are able to motivate the use of shrinkage estimators for modifying the B-H procedure. Several generalizations in the paper are discussed, and the methodology is applied to real and simulated datasets.

Shrinkage In Adaptive Procedures For False Discovery Rate Estimation In Multiple Testing: Structure And Synthesis, Debashis Ghosh

Debashis Ghosh

There has been much interest in the study of adaptive estimation procedures for controlling the false discovery rate (FDR). In this article, we take the direct approach to estimation of FDR of Storey (2002) and show how it can reexpressed as a particular type of shrinkage estimator. This representation leads to natural conditions on finite-sample FDR control for a general class of shrinkage estimators. In addition, many previous proposals from the literature can be unified under this framework for which finite-sample FDR results can be developed. Some asymptotic results are also provided.

An Epidemiological Model Of Rift Valley Fever With Spatial Dynamics, Tianchan Niu, Holly D. Gaff, Yiannis E. Papelis, David M. Hartley

Biological Sciences Faculty Publications

As a category A agent in the Center for Disease Control bioterrorism list, Rift Valley fever (RVF) is considered a major threat to the United States (USA). Should the pathogen be intentionally or unintentionally introduced to the continental USA, there is tremendous potential for economic damages due to loss of livestock, trade restrictions, and subsequent food supply chain disruptions. We have incorporated the effects of space into a mathematical model of RVF in order to study the dynamics of the pathogen spread as affected by the movement of humans, livestock, and mosquitoes. The model accounts for the horizontal transmission of …

Introducing Functional Data Analysis To Neuroimaging, And Vice Versa, Philip T. Reiss

Philip T. Reiss

No abstract provided.

The Use Of Imputed Values In The Meta-Analysis Of Genome-Wide Association Studies., Shuo Jiao, Li Hsu, Carolyn Hutter, Ulrike Peters

Shuo Jiao

In genome-wide association studies (GWAS), it is a common practice to impute the genotypes of untyped single nucleotide polymorphism (SNP) by exploiting the linkage disequilibrium structure among SNPs. The use of imputed genotypes improves genome coverage and makes it possible to perform meta-analysis combining results from studies genotyped on different platforms. A popular way of using imputed data is the "expectation-substitution" method, which treats the imputed dosage as if it were the true genotype. In current practice, the estimates given by the expectation-substitution method are usually combined using inverse variance weighting (IVM) scheme in meta-analysis. However, the IVM is not …

Meta-Analysis Of New Genome-Wide Association Studies Of Colorectal Cancer Risk.

Shuo Jiao

Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the …

Massively Parallel Nonparametrics [Hds 2011 Slides], Philip T. Reiss, Lei Huang

Philip T. Reiss

No abstract provided.

Social Marketing, Stages Of Change, And Public Health Smoking Interventions, Paula Diehr

Paula Diehr

As a "thought experiment," the authors used a modified stages of change model for smoking to define homogeneous segments within various hypothetical populations. The authors then estimated the population effect of public health interventions that targeted the different segments. Under most assumptions, interventions that emphasized primary and secondary prevention, by targeting the Never Smoker, Maintenance, or Action segments, resulted in the highest nonsmoking life expectancy. This result is consistent with both social marketing and public health principles. Although the best thing for an individual smoker is to stop smoking, the greatest public health benefit is achieved by interventions that target …

Flexible Dependence Of Functional Responses On Scalar Predictors, Philip T. Reiss, Lei Huang

Philip T. Reiss

No abstract provided.

Computational Analyses Of The Uptake And Distribution Of Carbon Monoxide (Co) In Human Subjects, Kinnera Chada

University of Kentucky Doctoral Dissertations

Carbon monoxide (CO) is an odorless, colorless, tasteless gas that binds to hemoglobin with high affinity. This property underlies the use of low doses of CO to determine hemoglobin mass (M_Hb) in the fields of clinical and sports medicine. However, hemoglobin bound to CO is unable to transport oxygen and exposure to high CO concentrations is a significant environmental and occupational health concern. These contrasting aspects of CO—clinically useful in low doses but potentially lethal in higher doses—mandates a need for a quantitative understanding of the temporal profiles of the uptake and distribution of CO …

Prevalence Of Piscine Myocarditis Virus (Pmcv) In Marine Fish Species, Torstein Tengs Dr.

Dr. Torstein Tengs

No abstract.