Life Sciences Commons^™

Functional Car Models For Spatially Correlated Functional Datasets, Lin Zhang, Veerabhadran Baladandayuthapani, Hongxiao Zhu, Keith A. Baggerly, Tadeusz Majewski, Bogdan Czerniak, Jeffrey S. Morris

Jeffrey S. Morris

We develop a functional conditional autoregressive (CAR) model for spatially correlated data for which functions are collected on areal units of a lattice. Our model performs functional response regression while accounting for spatial correlations with potentially nonseparable and nonstationary covariance structure, in both the space and functional domains. We show theoretically that our construction leads to a CAR model at each functional location, with spatial covariance parameters varying and borrowing strength across the functional domain. Using basis transformation strategies, the nonseparable spatial-functional model is computationally scalable to enormous functional datasets, generalizable to different basis functions, and can be used on …

Ordinal Probit Wavelet-Based Functional Models For Eqtl Analysis, Mark J. Meyer, Jeffrey S. Morris, Craig P. Hersh, Jarret D. Morrow, Christoph Lange, Brent A. Coull

Jeffrey S. Morris

Current methods for conducting expression Quantitative Trait Loci (eQTL) analysis are limited in scope to a pairwise association testing between a single nucleotide polymorphism (SNPs) and expression probe set in a region around a gene of interest, thus ignoring the inherent between-SNP correlation. To determine association, p-values are then typically adjusted using Plug-in False Discovery Rate. As many SNPs are interrogated in the region and multiple probe-sets taken, the current approach requires the fitting of a large number of models. We propose to remedy this by introducing a flexible function-on-scalar regression that models the genome as a functional outcome. The …

Bayesian Joint Selection Of Genes And Pathways: Applications In Multiple Myeloma Genomics, Lin Zhang, Jeffrey S. Morris, Jiexin Zhang, Robert Orlowski, Veerabhadran Baladandayuthapani

Jeffrey S. Morris

It is well-established that the development of a disease, especially cancer, is a complex process that results from the joint effects of multiple genes involved in various molecular signaling pathways. In this article, we propose methods to discover genes and molecular pathways significantly associ- ated with clinical outcomes in cancer samples. We exploit the natural hierarchal structure of genes related to a given pathway as a group of interacting genes to conduct selection of both pathways and genes. We posit the problem in a hierarchical structured variable selection (HSVS) framework to analyze the corresponding gene expression data. HSVS methods conduct …

A Study Of Mexican Free-Tailed Bat Chirp Syllables: Bayesian Functional Mixed Modeling Of Nonstationary Time Series Data With Time-Dependent Spectra, Josue G. Martinez, Kirsten M. Bohn, Raymond J. Carroll, Jeffrey S. Morris

Jeffrey S. Morris

We describe a new approach to analyze chirp syllables of free-tailed bats from two regions of Texas in which they are predominant: Austin and College Station. Our goal is to characterize any systematic regional differences in the mating chirps and assess whether individual bats have signature chirps. The data are analyzed by modeling spectrograms of the chirps as responses in a Bayesian functional mixed model. Given the variable chirp lengths, we compute the spectrograms on a relative time scale interpretable as the relative chirp position, using a variable window overlap based on chirp length. We use 2D wavelet transforms to …

Global Quantitative Assessment Of The Colorectal Polyp Burden In Familial Adenomatous Polyposis Using A Web-Based Tool, Patrick M. Lynch, Jeffrey S. Morris, William A. Ross, Miguel A. Rodriguez-Bigas, Juan Posadas, Rossa Khalaf, Diane M. Weber, Valerie O. Sepeda, Bernard Levin, Imad Shureiqi

Jeffrey S. Morris

Background: Accurate measures of the total polyp burden in familial adenomatous polyposis (FAP) are lacking. Current assessment tools include polyp quantitation in limited-field photographs and qualitative total colorectal polyp burden by video.

Objective: To develop global quantitative tools of the FAP colorectal adenoma burden.

Design: A single-arm, phase II trial.

Patients: Twenty-seven patients with FAP.

Intervention: Treatment with celecoxib for 6 months, with before-treatment and after-treatment videos posted to an intranet with an interactive site for scoring.

Main Outcome Measurements: Global adenoma counts and sizes (grouped into categories: less than 2 mm, 2-4 mm, and greater than 4 mm) were …

Piscine Myocarditis Virus (Pmcv) In Wild Atlantic Salmon Salmo Salar, Torstein Tengs Dr.

Dr. Torstein Tengs

Cardiomyopathy syndrome (CMS) is a severe cardiac disease of sea-farmed Atlantic salmon Salmo salar L., but CMS-like lesions have also been found in wild Atlantic salmon. In 2010 a double-stranded RNA virus of the Totiviridae family, provisionally named piscine myocarditis virus (PMCV), was described as the causative agent of CMS. In the present paper we report the first detection of PMCV in wild Atlantic salmon. The study is based on screening of 797 wild Atlantic salmon by real-time RT-PCR. The samples were collected from 35 different rivers along the coast of Norway, and all individuals included in the study were …

Prevalence Of Tick Borne Encephalitis Virus In Tick Nymphs In Relation To Climatic Factors On The Southern Coast Of Norway, Torstein Tengs Dr.

Dr. Torstein Tengs

BACKGROUND

Tick-borne encephalitis (TBE) is among the most important vector borne diseases of humans in Europe and is currently identified as a major health problem in many countries. TBE endemic zones have expanded over the past two decades, as well as the number of reported cases within endemic areas. Multiple factors are ascribed for the increased incidence of TBE, including climatic change. The number of TBE cases has also increased in Norway over the past decade, and the human cases cluster along the southern coast of Norway. In Norway the distribution and prevalence of TBE virus (TBEV) in tick populations …

Technical Factors Utilised By Elite Archers: Towards Setting An Agenda For Archery, Andrew J. Callaway, Shelley A. Broomfield

Andrew J Callaway

Archery, in one form or another, has been around for thousands of years yet research into what makes an archer 'good' is still in its infancy. There are several variations over bow type and different competitions which can be competed, previous works have focused on Recurve (Olympic) bow types whilst Compound have generally been ignored. Research in the area has tended to focus on muscle activation patterns using Electromyography (EMG) and aiming based studies, where generally scores are used as a factor to correlate to.

AIM: The aim of this research is to offer a development from the use of …

Data Mining Of Portable Eeg Brain Wave Signals For Sports Performance Analysis: An Archery Case Study, Matthew Casey, Alan Yau, Andrew J. Callaway, Keith Barfoot

Andrew J Callaway

No abstract provided.

A Strain Of Piscine Myocarditis Virus (Pmcv) Infecting Argentina Silus (Ascanius), Torstein Tengs Dr.

Dr. Torstein Tengs

No abstract.

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 …

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 …

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.

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 …

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

Dr. Torstein Tengs

No abstract.

Generalized Benjamini-Hochberg Procedures Using Spacings, Debashis Ghosh

Debashis Ghosh

For the problem of multiple testing, the Benjamini-Hochberg (B-H) procedure has become a very popular method in applications. We show how the B-H procedure can be interpreted as a test based on the spacings corresponding to the p-value distributions. Using this equivalence, we develop a class of generalized B-H procedures that maintain control of the false discovery rate in finite-samples. We also consider the effect of correlation on the procedure; simulation studies are used to illustrate the methodology.

A Causal Framework For Surrogate Endpoints With Semi-Competing Risks Data, Debashis Ghosh

Debashis Ghosh

In this note, we address the problem of surrogacy using a causal modelling framework that differs substantially from the potential outcomes model that pervades the biostatistical literature. The framework comes from econometrics and conceptualizes direct effects of the surrogate endpoint on the true endpoint. While this framework can incorporate the so-called semi-competing risks data structure, we also derive a fundamental non-identifiability result. Relationships to existing causal modelling frameworks are also discussed.

Propensity Score Modelling In Observational Studies Using Dimension Reduction Methods, Debashis Ghosh

Debashis Ghosh

Conditional independence assumptions are very important in causal inference modelling as well as in dimension reduction methodologies. These are two very strikingly different statistical literatures, and we study links between the two in this article. The concept of covariate sufficiency plays an important role, and we provide theoretical justication when dimension reduction and partial least squares methods will allow for valid causal inference to be performed. The methods are illustrated with application to a medical study and to simulated data.

A Novel Totivirus And Piscine Reovirus (Prv) In Atlantic Salmon (Salmo Salar) With Cardiomyopathy Syndrome (Cms), Torstein Tengs

Dr. Torstein Tengs

BACKGROUNDCardiomyopathy syndrome (CMS) is a severe disease affecting large farmed Atlantic salmon. Mortality often appears without prior clinical signs, typically shortly prior to slaughter. We recently reported the finding and the complete genomic sequence of a novel piscine reovirus (PRV), which is associated with another cardiac disease in Atlantic salmon; heart and skeletal muscle inflammation (HSMI). In the present work we have studied whether PRV or other infectious agents may be involved in the etiology of CMS.RESULTSUsing high throughput sequencing on heart samples from natural outbreaks of CMS and from fish experimentally challenged with material from fish diagnosed with CMS …

Heart And Skeletal Muscle Inflammation Of Farmed Salmon Is Associated With Infection With A Novel Reovirus, Torstein Tengs

Dr. Torstein Tengs

Atlantic salmon (Salmo salar L.) mariculture has been associated with epidemics of infectious diseases that threaten not only local production, but also wild fish coming into close proximity to marine pens and fish escaping from them. Heart and skeletal muscle inflammation (HSMI) is a frequently fatal disease of farmed Atlantic salmon. First recognized in one farm in Norway in 1999, HSMI was subsequently implicated in outbreaks in other farms in Norway and the United Kingdom. Although pathology and disease transmission studies indicated an infectious basis, efforts to identify an agent were unsuccessful. Here we provide evidence that HSMI is associated …

Non-Prejudiced Detection And Characterization Of Genetic Modifications, Torstein Tengs

Dr. Torstein Tengs

The application of gene technology is becoming widespread much thanks to the rapid increase in technology, resource, and knowledge availability. Consequently, the diversity and number of genetically modified organisms (GMOs) that may find their way into the food chain or the environment, intended or unintended, is rapidly growing. From a safety point of view the ability to detect and characterize in detail any GMO, independent of publicly available information, is fundamental. Pre-release risk assessments of GMOs are required in most jurisdictions and are usually based on application of technologies with limited ability to detect unexpected rearrangements and insertions. We present …

Comparison Of Nine Different Real-Time Pcr Chemistries For Qualitative And Quantitative Applications In Gmo Detection, Torstein Tengs

Dr. Torstein Tengs

Several techniques have been developed for detection and quantification of genetically modified organisms, but quantitative real-time PCR is by far the most popular approach. Among the most commonly used realtime PCR chemistries are TaqMan probes and SYBR green, but many other detection chemistries have also been developed. Because their performance has never been compared systematically, here we present an extensive evaluation of some promising chemistries: sequenceunspecific DNA labeling dyes (SYBR green), primer-based technologies (AmpliFluor, Plexor, Lux primers), and techniques involving double-labeled probes, comprising hybridization (molecular beacon) and hydrolysis (TaqMan, CPT, LNA, and MGB) probes, based on recently published experimental data. …

Manifest Greatness The Final Original Version By Emmanuel Mario B Santos Aka Marc Guerrero, Emmanuel Mario B. Santos Aka Marc Guerrero

Emmanuel Mario B Santos aka Marc Guerrero

MANIFEST GREATNESS vf24jan2010 WE COME TOGETHER THERE OUGHT TO BE NO POOR WE TAKE CHARGE.

Wavelet-Based Functional Linear Mixed Models: An Application To Measurement Error–Corrected Distributed Lag Models, Elizabeth J. Malloy, Jeffrey S. Morris, Sara D. Adar, Helen Suh, Diane R. Gold, Brent A. Coull

Jeffrey S. Morris

Frequently, exposure data are measured over time on a grid of discrete values that collectively define a functional observation. In many applications, researchers are interested in using these measurements as covariates to predict a scalar response in a regression setting, with interest focusing on the most biologically relevant time window of exposure. One example is in panel studies of the health effects of particulate matter (PM), where particle levels are measured over time. In such studies, there are many more values of the functional data than observations in the data set so that regularization of the corresponding functional regression coefficient …

Members’ Discoveries: Fatal Flaws In Cancer Research, Jeffrey S. Morris

Jeffrey S. Morris

A recent article published in The Annals of Applied Statistics (AOAS) by two MD Anderson researchers—Keith Baggerly and Kevin Coombes—dissects results from a highly-influential series of medical papers involving genomics-driven personalized cancer therapy, and outlines a series of simple yet fatal flaws that raises serious questions about the veracity of the original results. Having immediate and strong impact, this paper, along with related work, is providing the impetus for new standards of reproducibility in scientific research.

Statistical Contributions To Proteomic Research, Jeffrey S. Morris, Keith A. Baggerly, Howard B. Gutstein, Kevin R. Coombes

Jeffrey S. Morris

Proteomic profiling has the potential to impact the diagnosis, prognosis, and treatment of various diseases. A number of different proteomic technologies are available that allow us to look at many proteins at once, and all of them yield complex data that raise significant quantitative challenges. Inadequate attention to these quantitative issues can prevent these studies from achieving their desired goals, and can even lead to invalid results. In this chapter, we describe various ways the involvement of statisticians or other quantitative scientists in the study team can contribute to the success of proteomic research, and we outline some of the …

Informatics And Statistics For Analyzing 2-D Gel Electrophoresis Images, Andrew W. Dowsey, Jeffrey S. Morris, Howard G. Gutstein, Guang Z. Yang

Jeffrey S. Morris

Whilst recent progress in ‘shotgun’ peptide separation by integrated liquid chromatography and mass spectrometry (LC/MS) has enabled its use as a sensitive analytical technique, proteome coverage and reproducibility is still limited and obtaining enough replicate runs for biomarker discovery is a challenge. For these reasons, recent research demonstrates the continuing need for protein separation by two-dimensional gel electrophoresis (2-DE). However, with traditional 2-DE informatics, the digitized images are reduced to symbolic data though spot detection and quantification before proteins are compared for differential expression by spot matching. Recently, a more robust and automated paradigm has emerged where gels are directly …

Bayesian Random Segmentationmodels To Identify Shared Copy Number Aberrations For Array Cgh Data, Veerabhadran Baladandayuthapani, Yuan Ji, Rajesh Talluri, Luis E. Nieto-Barajas, Jeffrey S. Morris

Jeffrey S. Morris

Array-based comparative genomic hybridization (aCGH) is a high-resolution high-throughput technique for studying the genetic basis of cancer. The resulting data consists of log fluorescence ratios as a function of the genomic DNA location and provides a cytogenetic representation of the relative DNA copy number variation. Analysis of such data typically involves estimation of the underlying copy number state at each location and segmenting regions of DNA with similar copy number states. Most current methods proceed by modeling a single sample/array at a time, and thus fail to borrow strength across multiple samples to infer shared regions of copy number aberrations. …