Physical Sciences and Mathematics Commons^™

Fuzzy Logistic Regression For Detecting Differential Dna Methylation Regions, Tarek M. Bubaker Bennaser

Doctoral Dissertations

“Epigenetics is the study of changes in gene activity or function that are not related to a change in the DNA sequence. DNA methylation is one of the main types of epigenetic modifications, that occur when a methyl chemical group attaches to a cytosine on the DNA sequence. Although the sequence does not change, the addition of a methyl group can change the way genes are expressed and produce different phenotypes. DNA methylation is involved in many biological processes and has important implications in the fields of biomedicine and agriculture.

Statistical methods have been developed to compare DNA methylation at …

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.

Mu Transposon Insertion Sites And Meiotic Recombination Events Co-Localize With Epigenetic Marks For Open Chromatin Across The Maize Genome, Sanzhen Liu, Cheng-Ting Yeh, Tieming Ji, Kai Ying, Haiyan Wu, Ho Man Tang, Yan Fu, Daniel S. Nettleton, Patrick S. Schnable

Dan Nettleton

The Mu transposon system of maize is highly active, with each of the ∼50–100 copies transposing on average once each generation. The approximately one dozen distinct Mutransposons contain highly similar ∼215 bp terminal inverted repeats (TIRs) and generate 9-bp target site duplications (TSDs) upon insertion. Using a novel genome walking strategy that uses these conserved TIRs as primer binding sites, Mu insertion sites were amplified from Mu stocks and sequenced via 454 technology. 94% of ∼965,000 reads carried Mu TIRs, demonstrating the specificity of this strategy. Among these TIRs, 21 novel Mu TIRs were discovered, revealing additional complexity of …

Genetics Analysis Workshop 20: Methods And Strategies For The New Frontiers Of Epigenetics And Pharmacogenomics, Nathan L. Tintle, David W. Fardo, Mariza De Andrade, Stella Aslibekyan, Julia N. Bailey, Justo Lorenzo Bermejo, Rita M. Cantor, Saurabh Ghosh, Philip Melton, Xuexia Wang, Jean W. Maccluer, Laura Almasy

Faculty Work Comprehensive List

GAW20 provided a platform for developing and evaluating statistical methods to analyze human lipid-related phenotypes, DNA methylation, and single-nucleotide markers in a study involving a pharmaceutical intervention. In this article, we present an overview of the data sets and the contributions analyzing these data. The data, donated by the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) investigators, included data from 188 families (N = 1105) which included genome-wide DNA methylation data before and after a 3-week treatment with fenofibrate, single-nucleotide polymorphisms, metabolic syndrome components before and after treatment, and a variety of covariates. The contributions from individual …

Gaw20: Methods And Strategies For The New Frontiers Of Epigenetics And Pharmacogenomics, Nathan L. Tintle, David W. Fardo, Marzia De Andrade, Stella Aslibekyan, Julia N. Bailey, Justo Lorenzo Bermejo, Rita M. Cantor, Saurabh Ghosh, Philip Melton, Xuexua Wang, Jean W. Maccluer, Laura Almasy

Biostatistics Faculty Publications

GAW20 provided a platform for developing and evaluating statistical methods to analyze human lipid-related phenotypes, DNA methylation, and single-nucleotide markers in a study involving a pharmaceutical intervention. In this article, we present an overview of the data sets and the contributions analyzing these data. The data, donated by the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) investigators, included data from 188 families (N = 1105) which included genome-wide DNA methylation data before and after a 3-week treatment with fenofibrate, single-nucleotide polymorphisms, metabolic syndrome components before and after treatment, and a variety of covariates. The contributions from individual …

Longitudinal Data Methods For Evaluating Genome-By-Epigenome Interactions In Families, Justin C. Strickland, I-Chen Chen, Chanung Wang, David W. Fardo

Psychology Faculty Publications

Background: Longitudinal measurement is commonly employed in health research and provides numerous benefits for understanding disease and trait progression over time. More broadly, it allows for proper treatment of correlated responses within clusters. We evaluated 3 methods for analyzing genome-by-epigenome interactions with longitudinal outcomes from family data.

Results: Linear mixed-effect models, generalized estimating equations, and quadratic inference functions were used to test a pharmacoepigenetic effect in 200 simulated posttreatment replicates. Adjustment for baseline outcome provided greater power and more accurate control of Type I error rates than computation of a pre-to-post change score.

Conclusions: Comparison of all modeling approaches indicated …

Multiple Testing Correction With Repeated Correlated Outcomes: Applications To Epigenetics, Katie Leap

Masters Theses

Epigenetic changes (specifically DNA methylation) have been associated with adverse health outcomes; however, unlike genetic markers that are fixed over the lifetime of an individual, methylation can change. Given that there are a large number of methylation sites, measuring them repeatedly introduces multiple testing problems beyond those that exist in a static genetic context. Using simulations of epigenetic data, we considered different methods of controlling the false discovery rate. We considered several underlying associations between an exposure and methylation over time.

We found that testing each site with a linear mixed effects model and then controlling the false discovery rate …

Sex-Specific Hippocampal 5-Hydroxymethylcytosine Is Disrupted In Response To Acute Stress, Ligia A. Papale, Sisi Li, Andy Madrid, Qi Zhang, Li Chen, Pankaj Chopra, Peng Jin, Sunduz Keles, Reid S. Alisch

Department of Statistics: Faculty Publications

Environmental stress is among the most important contributors to increased susceptibility to develop psychiatric disorders. While it is well known that acute environmental stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive epigenetic modification that is highly enriched in neurons and is associated with active neuronal transcription. Recently,we reported a genome-wide disruption of hippocampal 5hmCin male mice following acute stress that was correlated to altered transcript levels of genes in known stress related pathways. Since sex-specific endocrine mechanisms respond to environmental stimulus by altering the neuronal epigenome, we examined …

Methods For Integrative Analysis Of Genomic Data, Paul Manser

Theses and Dissertations

In recent years, the development of new genomic technologies has allowed for the investigation of many regulatory epigenetic marks besides expression levels, on a genome-wide scale. As the price for these technologies continues to decrease, study sizes will not only increase, but several different assays are beginning to be used for the same samples. It is therefore desirable to develop statistical methods to integrate multiple data types that can handle the increased computational burden of incorporating large data sets. Furthermore, it is important to develop sound quality control and normalization methods as technical errors can compound when integrating multiple genomic …

Age-Specific Signatures Of Glioblastoma At The Genomic, Genetic, And Epigenetic Levels, Serdar Bozdag, Aiguo Li, Gregory Riddick, Yuri Kotliarov, Mehmet Baysan, Fabio M. Iwamoto, Margaret C. Cam, Svetlana Kotliarova, Howard A. Fine

Mathematics, Statistics and Computer Science Faculty Research and Publications

Age is a powerful predictor of survival in glioblastoma multiforme (GBM) yet the biological basis for the difference in clinical outcome is mostly unknown. Discovering genes and pathways that would explain age-specific survival difference could generate opportunities for novel therapeutics for GBM. Here we have integrated gene expression, exon expression, microRNA expression, copy number alteration, SNP, whole exome sequence, and DNA methylation data sets of a cohort of GBM patients in The Cancer Genome Atlas (TCGA) project to discover age-specific signatures at the transcriptional, genetic, and epigenetic levels and validated our findings on the REMBRANDT data set. We found major …

Anticancer Peptidylarginine Deiminase (Pad) Inhibitors Regulate The Autophagy Flux And The Mammalian Target Of Rapamycin Complex 1 Activity, Yuji Wang, Pingxin Li, Shu Wang, Jing Hu, Xiangyun Amy Chen, Jianhui Wu, Megan Fisher, Kira Oshaben, Na Zhao, Ying Gu, Dong Wang, Gong Chen, Yanming Wang

Department of Statistics: Faculty Publications

Tumor suppressor genes are frequently silenced in cancer cells by enzymes catalyzing epigenetic histone modifications. The peptidylarginine deiminase family member PAD4 (also called PADI4) is markedly overexpressed in a majority of human cancers, suggesting that PAD4 is a putative target for cancer treatment. Here, we have generated novel PAD inhibitors with low micromolar IC₅₀ in PAD activity and cancer cell growth inhibition. The lead compound YW3-56 alters the expression of genes controlling the cell cycle and cell death, including SESN2 that encodes an upstream inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Guided by the …

Prediction Of Dna Methylation Based On Genomic Architecture And Applications Of Positional Weight Matrices, Juan Gallegos

Dissertations & Theses (Open Access)

Gene silencing due to epigenetic mechanisms shows evidence of significant contributions to cancer development. We hypothesis that the genetic architecture based on retrotransposon elements surrounding the transcription start site, plays an important role in the suppression and promotion of DNA methylation. In our investigation we found a high rate of SINE and LINEs retrotransposon elements near the transcription start site of unmethylated genes when compared to methylated genes. The presence of these elements were positively associated with promoter methylation, contrary to logical expectations, due to the malicious effects of retrotransposon elements which insert themselves randomly into the genome causing possible …

Dna Methylation And Its Association With Prenatal Exposures And Pregnancy Outcomes, Jennifer Straughen

USF Tampa Graduate Theses and Dissertations

Altered DNA methylation may lead to suboptimal fetal programming, increasing the risk of adverse pregnancy outcomes such as small for gestational age (SGA); however, few studies have examined the associations between DNA methylation, prenatal exposures, and fetal outcomes. Cross-sectional data from a larger, ongoing study were used to assess the impact of prenatal smoking on gene specific methylation of umbilical cord blood derived DNA and to investigate the association between gene-specific methylation and risk of SGA. The association between gene-specific DNA methylation and birthweight was also assessed. Maternal and infant covariates were abstracted from medical records, cigarette smoke exposure was …

A Two-Stage Approach For Estimating The Effect Of Dna Methylation On Differential Expression Using Tiling Array Technology, Suk-Young Yoo, R. W. Doerge

Conference on Applied Statistics in Agriculture

Epigenetics is the study of heritable alterations in gene function without changing the DNA sequence itself. It is known that epigenetic modifications such as DNA methylation and histone modifications are highly correlated with the regulation of gene expression. A twostage analysis is proposed that employs a hidden Markov model and a linear model to evaluate differential expression as related to DNA methylation for the purpose of examining the effects of DNA methylation on gene regulation using tiling array technology. In the first stage, a hidden Markov model (HMM) is employed to estimate the methylation status per tile by utilizing information …