Comparison Of Nine Different Real-Time Pcr Chemistries For Qualitative And Quantitative Applications In Gmo Detection,
2010
Norwegian Veterinary Institute
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. …
Prevalence, Incidence, And Persistence Of Major Depressive Symptoms In The Cardiovascular Health Study,
2010
University of Washington
Prevalence, Incidence, And Persistence Of Major Depressive Symptoms In The Cardiovascular Health Study, Stephen M. Thielke Md, Ms, Paula Diehr Phd
Paula Diehr
PURPOSE: To explore the association of major depressive symptoms with advancing age, sex, and self-rated health among older adults. DESIGN AND METHODS: We analyzed 10 years of annual assessments in a longitudinal cohort of 5888 Medicare recipients in the Cardiovascular Health Study. Self-rated health was assessed with a single question, and subjects categorized as healthy or sick. Major depressive symptoms were assessed using the Center for Epidemiologic Studies Short Depression Scale, with subjects categorized as nondepressed (score < 10) or depressed (> or =10). Age-, sex-, and health-specific prevalence of depression and the probabilities of transition between depressed and nondepressed states were estimated. RESULTS: The …
A Mixture Model Based Approach For Estimating The Fdr In Replicated Microarray Data,
2010
Fred Hutchinson Cancer Research Center
A Mixture Model Based Approach For Estimating The Fdr In Replicated Microarray Data, Shuo Jiao, Shunpu Zhang
Shuo Jiao
One of the mostly used methods for estimating the false discovery rate (FDR) is the permutation based method. The permutation based method has the well-known granularity problem due to the discrete nature of the permuted null scores. The granularity problem may produce very unstable FDR estimates. Such instability may cause scientists to over- or under-estimate the number of false positives among the genes declared as significant, and hence result in inaccurate interpretation of biological data. In this paper, we propose a new model based method as an improvement of the permutation based FDR estimation method of SAM [1] The new …
Event Adjudication Changes Key Results In Open-Label Trials: The Affirm Experience,
2010
Axio Research
Event Adjudication Changes Key Results In Open-Label Trials: The Affirm Experience, Elaine M. Nasco, April Slee, Kent M. Koprowicz, Robert G. Hart
Kent M Koprowicz
Event Adjudication Changes Key Results in Open-Label Trials: The AFFIRM Experience Author Block: Elaine M. Nasco, April Slee, Kent Koprowicz, Robert G. Hart, Axio Research, LLC, Seattle, WA Abstract: Background: The value of central event adjudication of endpoints in multi-center randomized trials has recently been questioned. Methods: The NIH-sponsored Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial randomized 4,060 atrial fibrillation patients to antiarrhythmic drugs (rhythm control) vs. rate-controlling drugs, given open-label, at 213 clinical sites. While the primary outcome was mortality, a key secondary endpoint was ischemic stroke (IS), centrally adjudicated by those reviewing source documents from which …
Functional Generalized Linear Models With Images As Predictors,
2010
New York University
Functional Generalized Linear Models With Images As Predictors, Philip T. Reiss, R. Todd Ogden
Philip T. Reiss
Functional principal component regression (FPCR) is a promising new method for regressing scalar outcomes on functional predictors. In this paper we present a theoretical justification for the use of principal components in functional regression. FPCR is then extended in two directions: from linear to the generalized linear modeling, and from univariate signal predictors to high-resolution image predictors. We show how to implement the method efficiently by adapting generalized additive model technology to the functional regression context. A technique is proposed for estimating simultaneous confidence bands for the coefficient function; in the neuroimaging setting, this yields a novel means to identify …
Estimating The Proportion Of Equivalently Expressed Genes In Microarray Data Based On Transformed Test Statistics,
2010
Fred Hutchinson Cancer Research Center
Estimating The Proportion Of Equivalently Expressed Genes In Microarray Data Based On Transformed Test Statistics, Shuo Jiao, Shunpu Zhang
Shuo Jiao
In microarray data analysis, false discovery rate (FDR) is now widely accepted as the control criterion to account for multiple hypothesis testing. The proportion of equivalently expressed genes (π0) is a key component to be estimated in the estimation of FDR. Some commonly used π0 estimators (BUM, SPLOSH, QVALUE, and LBE ) are all based on p-values, and they are essentially upper bounds of π0. The simulations we carried out show that these four methods significantly overestimate the true π0 when differentially expressed genes and equivalently expressed genes are not well separated. To solve this problem, we first introduce a …
Wavelet-Based Functional Linear Mixed Models: An Application To Measurement Error–Corrected Distributed Lag Models,
2010
American University
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,
2010
The University of Texas M.D. Anderson Cancer Center
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,
2010
The University of Texas M.D. Anderson Cancer Center
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,
2010
Imperial College London
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,
2010
Texas A&M University
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. …
Code For Fitting Bdsacgh,
2010
UT MD Anderson Cancer Center
Code For Fitting Bdsacgh, Veera Baladandayuthapani
Veera Baladandayuthapani
No abstract provided.
R Package For Bayesian Ensemble Methods For Survival Prediction In Gene Expression Data,
2010
UT MD Anderson Cancer Center
R Package For Bayesian Ensemble Methods For Survival Prediction In Gene Expression Data, Veera Baladandayuthapani
Veera Baladandayuthapani
This is the R package for the methods described in Bayesian ensemble methods for survival prediction in gene expression data by Vinicius Bonato , Veerabhadran Baladandayuthapani, Kim-Anh Do, Bradley M. Broom, Erik P. Sulman, and Kenneth D. Aldape Submitted to Bioinformatics (2010)
Bayesian Random Segmentationmodels To Identify Shared Copy Number Aberrations For Array Cgh Data,
2010
UT MD Anderson Cancer Center
Bayesian Random Segmentationmodels To Identify Shared Copy Number Aberrations For Array Cgh Data, Veera Baladandayuthapani
Veera Baladandayuthapani
No abstract provided.
Identification Of Ovarian Cancer Symptoms In Health Insurance Claims Data.,
2010
University of Washington
Identification Of Ovarian Cancer Symptoms In Health Insurance Claims Data., Paula Diehr, Sean Devlin
Paula Diehr
Background: Women with ovarian cancer have reported abdominal=pelvic pain, bloating, difficulty eating or feeling full quickly, and urinary frequency=urgency prior to diagnosis. We explored these findings in a general population using a dataset of insured women aged 40–64 and investigated the potential effectiveness of a routine review of claims data as a prescreen to identify women at high risk for ovarian cancer. Methods: Data from a large Washington State health insurer were merged with the Seattle-Puget Sound Surveillance, Epidemiology and End Results (SEER) cancer registry for 2000–2004. We estimated the prevalence of symptoms in the 36 months prior to diagnosis …
Targeted Maximum Likelihood Estimation Of The Parameter Of A Marginal Structural Model,
2010
Johns Hopkins University
Targeted Maximum Likelihood Estimation Of The Parameter Of A Marginal Structural Model, Michael Rosenblum, Mark J. Van Der Laan
Michael Rosenblum
Targeted maximum likelihood estimation is a versatile tool for estimating parameters in semiparametric and nonparametric models. We work through an example applying targeted maximum likelihood methodology to estimate the parameter of a marginal structural model. In the case we consider, we show how this can be easily done by clever use of standard statistical software. We point out differences between targeted maximum likelihood estimation and other approaches (including estimating function based methods). The application we consider is to estimate the effect of adherence to antiretroviral medications on virologic failure in HIV positive individuals.
Discrete Nonparametric Algorithms For Outlier Detection With Genomic Data,
2010
Penn State University
Discrete Nonparametric Algorithms For Outlier Detection With Genomic Data, Debashis Ghosh
Debashis Ghosh
In high-throughput studies involving genetic data such as from gene expression mi- croarrays, dierential expression analysis between two or more experimental conditions has been a very common analytical task. Much of the resulting literature on multiple comparisons has paid relatively little attention to the choice of test statistic. In this article, we focus on the issue of choice of test statistic based on a special pattern of dierential expression. The approach here is based on recasting multiple comparisons procedures for assessing outlying expression values. A major complication is that the resulting p-values are discrete; some theoretical properties of sequential testing …
Detecting Outlier Genes From High-Dimensional Data: A Fuzzy Approach,
2010
Penn State University
Detecting Outlier Genes From High-Dimensional Data: A Fuzzy Approach, Debashis Ghosh
Debashis Ghosh
A recent nding in cancer research has been the characterization of previously undis- covered chromosomal abnormalities in several types of solid tumors. This was found based on analyses of high-throughput data from gene expression microarrays and motivated the development of so-called `outlier' tests for dierential expression. One statistical issue was the potential discreteness of the test statistics. Using ideas from fuzzy set theory, we develop fuzzy outlier detection algorithms that have links to ideas in multiple comparisons. Two- and K-sample extensions are considered. The methodology is illustrated by application to two microarray studies.
Links Between Analysis Of Surrogate Endpoints And Endogeneity,
2010
Penn State University
Links Between Analysis Of Surrogate Endpoints And Endogeneity, Debashis Ghosh, Jeremy M. Taylor, Michael R. Elliott
Debashis Ghosh
There has been substantive interest in the assessment of surrogate endpoints in medical research. These are measures which could potentially replace \true" endpoints in clinical trials and lead to studies that require less follow-up. Recent research in the area has focused on assessments using causal inference frameworks. Beginning with a simple model for associating the surrogate and true endpoints in the population, we approach the problem as one of endogenous covariates. An instrumental variables estimator and general two-stage algorithm is proposed. Existing surrogacy frameworks are then evaluated in the context of the model. A numerical example is used to illustrate …
Meta-Analysis For Surrogacy: Accelerated Failure Time Models And Semicompeting Risks Modelling,
2010
Penn State University
Meta-Analysis For Surrogacy: Accelerated Failure Time Models And Semicompeting Risks Modelling, Debashis Ghosh, Jeremy M. Taylor, Daniel J. Sargent
Debashis Ghosh
There has been great recent interest in the medical and statistical literature in the assessment and validation of surrogate endpoints as proxies for clinical endpoints in medical studies. More recently, authors have focused on using meta-analytical methods for quanti cation of surrogacy. In this article, we extend existing procedures for analysis based on the accelerated failure time model to this setting. An advantage of this approach relative to proportional hazards model is that it allows for analysis in the semi-competing risks setting, where we constrain the surrogate endpoint to occur before the true endpoint. A novel principal components procedure is …
