Medicine and Health Sciences Commons^™

Genomic Tools Reveal Complex Social Organization Of An Invasive Large Mammal (Sus Scrofa), Chelsea L. Titus, Courtney F. Bowden, Timothy J. Smyser, Stephen L. Webb, James C. Beasley

USDA Wildlife Services: Staff Publications

A comprehensive understanding of sociality in wildlife is vital to optimizing conservation and management efforts. However, sociality is complicated, especially for widely distributed species that exhibit substantive behavioral plasticity. Invasive wild pigs (Sus scrofa), often representing hybrids of European wild boar and domestic pigs, are among the most adaptable and widely distributed large mammals. The social structure of wild pigs is believed to be similar to European wild boar, consisting of matriarchal groups (sounders) and solitary males. However, wild pig social structure is understudied and largely limited to visual observations. Using a hierarchical approach, we incorporated genomic tools …

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …

Epidemiological, Clinical And Genetic Aspects Of Adult Onset Isolated Focal Dystonia In Ireland, L. Williams, E. Mcgovern, O. Kimmich, A. Molloy, I. Beiser, John Butler, F. Molloy, P. Logan, D.G. Healy, T. Lynch, R. Walsh, L. Cassidy, P. Moriarty, H. Moore, T. Mcswiney, C. Walsh, S. O'Riordan, M. Hutchinson

Articles

Background: Adult onset idiopathic isolated focal dystonia presents with a number of phenotypes. Reported prevalence rates vary considerably; well-characterized cohorts are important to our understanding of this disorder.

Aim: To perform a nationwide epidemiological study of adult onset idiopathic isolated focal dystonia in the Republic of Ireland.

Methods: Patients with adult onset idiopathic isolated focal dystonia were recruited from multiple sources. Diagnosis was based on assessment by a neurologist with an expertise in movement disorders. When consent was obtained, a number of clinical features including family history were assessed.

Results: On the prevalence date there were 592 individuals in Ireland …

Inhibitions Of Gsk3Β Modulates Cell Death In Epithelial Ovarian Cancer, Noelle L. Cutter Ph.D., Tyler Walther Bsc, Naeha Pathak

Faculty Works: Biology, Chemistry, and Environmental Studies

Epithelial ovarian cancer is one of the most common gynecological malignancies and the fifth most frequent cause of cancer death in women, affecting over 22,000 women annually. Nearly 15,500 affected women die from this disease annually, and chemoresistance from the commonly prescribed platinum-based drug, carboplatin, is a major contributor to this mortality rate. Previous studies have identified genes with CpG islands that are methylated and transcriptionally silenced in resistant epithelial ovarian cancer patients. One of these genes is GSK3β, an important regulator of apoptosis and cell growth in the Wnt pathway. Thus, understanding the role of GSK3β suppression in chemoresistance …

Spectral Gene Set Enrichment (Sgse), H Robert Frost, Zhigang Li, Jason H. Moore

Dartmouth Scholarship

Gene set testing is typically performed in a supervised context to quantify the association between groups of genes and a clinical phenotype. In many cases, however, a gene set-based interpretation of genomic data is desired in the absence of a phenotype variable. Although methods exist for unsupervised gene set testing, they predominantly compute enrichment relative to clusters of the genomic variables with performance strongly dependent on the clustering algorithm and number of clusters. We propose a novel method, spectral gene set enrichment (SGSE), for unsupervised competitive testing of the association between gene sets and empirical data sources. SGSE first computes …

Abstract 2988: Dok2 Suppression By Methylation Induces Platinum Resistance Via Suppression Of Apoptosis In Ovarian Cancer Cells., Noelle L. Cutter Ph.D., Elena Lum, Michelle Vigliotti, Nilanjana Banerjee, Sitharthan Kamalakaran, Kazimierz O. Wrzeszczynski, Sohail Khan, Nevenka Dimitrova, Douglas A. Levine, Robert Lucito

Faculty Works: Biology, Chemistry, and Environmental Studies

Ovarian cancers are highly heterogeneous and while chemotherapy is the preferred treatment, many patients are intrinsically resistant or quickly develop resistance. Furthermore, all tumors that recur will become resistant. Recent evidence suggests that epigenetic deregulation may be a key factor in the onset and maintenance of chemoresistance. To examine the ovarian epigenome, we first analyzed a set of 43 primary ovarian tumors and 9 normal ovarian samples. Since therapy response is a significant issue for ovarian cancer patients we analyzed the epigenetic differences that segregate with platinum response. We then associated expression data to identify genes with expression changes potentially …

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.

Abstract 70: A Role For The Chromatin Remodeling Protein Chd3 In Ovarian Cancer Therapy Response, Noelle L. Cutter Ph.D., Nila Banerjee, Michelle Vigliotti, Angel Janevski, Douglas Levine, Robert Lucito, Nevenka Dimitrova

Faculty Works: Biology, Chemistry, and Environmental Studies

Carboplatin and cisplatin are chemotherapeutic agents that are used extensively for treating epithelial ovarian cancer. These drugs can be highly effective, yet tumors are frequently refractory to treatment or become resistant upon tumor relapse. Epigenetic silencing, particularly at promoter regions of genes regulates important cell function and has been associated with all stages of tumor formation and progression and may contribute to therapy response. We analyzed the epigenome of 50 primary ovarian tumors and 12 normal ovarian samples using an array based method previously developed in our lab and associated Affymetrix U133 expression data. We then identified gene candidates that …

Minimum Description Length And Empirical Bayes Methods Of Identifying Snps Associated With Disease, Ye Yang, David R. Bickel

COBRA Preprint Series

The goal of determining which of hundreds of thousands of SNPs are associated with disease poses one of the most challenging multiple testing problems. Using the empirical Bayes approach, the local false discovery rate (LFDR) estimated using popular semiparametric models has enjoyed success in simultaneous inference. However, the estimated LFDR can be biased because the semiparametric approach tends to overestimate the proportion of the non-associated single nucleotide polymorphisms (SNPs). One of the negative consequences is that, like conventional p-values, such LFDR estimates cannot quantify the amount of information in the data that favors the null hypothesis of no disease-association.

We …

Sheep Updates 2008 - Part 3, L. J. E. Karlsson, J. C. Greeff, L. Slocombe, K. Jones, N. Underwood, Fred Wilkinson, W. D. Hoffman, W. A. Mckiernan, V. H. Oddy, M. J. Mcphee, B. L. Mcintyre, P. F. Parnell, R. A. Clark, J. Timms, G. Griffith, C. Mulholland, P. Hyland, Danielle England, Fiona Jones, John Lucey, Martin Staines, Richard Morris, Megan Abrahams, Caroline Peek, Dennis Van Gool, Daniel Gardiner, Kari-Lee Falconer, Sandra Prosser, Mario D'Antuono, John Young, Andrew Thompson, Chris Oldham, Brown Besier, Angus Campbell, Ralph Behrendt

Sheep Updates

This session covers fiveteen papers from different authors:

CONTROLLING FLY STRIKE

1. Breeding for Blowfly Resistance - Indicatoe Traits, LJE Karlsson, JC Greeff, L Slocombe, Department of Agriculture & Food, Western Australia

2.A practical method to select for breech strike resistance in non-pedigreed Merino flocks, LJE Karlsson, JC Greeff, L Slocombe, K. Jones, N. Underwood, Department of Agriculture & Food, Western Australia

3. Twice a year shearing - no mulesing, Fred Wilkinson, Producer, Brookton WA

BEEF

4. Commercial testing of a new tool for prediction of fatness in beef cattle, WD Hoffman^A, WA McKiernan^A, VH Oddy …

Power Boosting In Genome-Wide Studies Via Methods For Multivariate Outcomes, Mary J. Emond

UW Biostatistics Working Paper Series

Whole-genome studies are becoming a mainstay of biomedical research. Examples include expression array experiments, comparative genomic hybridization analyses and large case-control studies for detecting polymorphism/disease associations. The tactic of applying a regression model to every locus to obtain test statistics is useful in such studies. However, this approach ignores potential correlation structure in the data that could be used to gain power, particularly when a Bonferroni correction is applied to adjust for multiple testing. In this article, we propose using regression techniques for misspecified multivariate outcomes to increase statistical power over independence-based modeling at each locus. Even when the outcome …

Semiparametric Regression Of Multi-Dimensional Genetic Pathway Data: Least Squares Kernel Machines And Linear Mixed Models, Dawei Liu, Xihong Lin, Debashis Ghosh

Harvard University Biostatistics Working Paper Series

No abstract provided.

Structural Inference In Transition Measurement Error Models For Longitudinal Data, Wenqin Pan, Xihong Lin, Donglin Zeng

Harvard University Biostatistics Working Paper Series

No abstract provided.

Nonparametric Regression Using Local Kernel Estimating Equations For Correlated Failure Time Data, Zhangsheng Yu, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Causal Inference In Hybrid Intervention Trials Involving Treatment Choice, Qi Long, Rod Little, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Comparison Of Methods For Estimating The Causal Effect Of A Treatment In Randomized Clinical Trials Subject To Noncompliance, Rod Little, Qi Long, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Gpnn: Power Studies And Applications Of A Neural Network Method For Detecting Gene-Gene Interactions In Studies Of Human Disease, Alison A. Motsinger, Stephen L. Lee, George Mellick, Marylyn D. Ritchie

Dartmouth Scholarship

The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease.

Filling Preposition-Based Templates To Capture Information From Medical Abstracts, Gondy Leroy, Hsinchun Chen

CGU Faculty Publications and Research

Due to the recent explosion of information in the biomedical field, it is hard for a single researcher to review the complex network involving genes, proteins, and interactions. We are currently building GeneScene, a toolkit that will assist researchers in reviewing existing literature, and report on the first phase in our development effort: extracting the relevant information from medical abstracts. We are developing a medical parser that extracts information, fills basic prepositional-based templates, and combines the templates to capture the underlying sentence logic. We tested our parser on 50 unseen abstracts and found that it extracted 246 templates with a …