Genetics and Genomics Commons^™

Meta-Analysis Of Genome-Wide Association Studies With Correlated Individuals: Application To The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Tamar Sofer, John R. Shaffer, Misa Graff, Qibin Qi, Adrienne M. Stilp, Stephanie M. Gogarten, Kari E. North, Carmen R. Isasi, Cathy C. Laurie, Adam A. Szpiro

UW Biostatistics Working Paper Series

Investigators often meta-analyze multiple genome-wide association studies (GWASs) to increase the power to detect associations of single nucleotide polymorphisms (SNPs) with a trait. Meta-analysis is also performed within a single cohort that is stratified by, e.g., sex or ancestry group. Having correlated individuals among the strata may complicate meta-analyses, limit power, and inflate Type 1 error. For example, in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), sources of correlation include genetic relatedness, shared household, and shared community. We propose a novel mixed-effect model for meta-analysis, “MetaCor", which accounts for correlation between stratum-specific effect estimates. Simulations show that MetaCor controls …

Mutations Of Adjacent Amino Acid Pairs Are Not Always Independent, Jyotsna Ramanan, Peter Revesz

CSE Conference and Workshop Papers

Evolutionary studies usually assume that the genetic mutations are independent of each other. This paper tests the independence hypothesis for genetic mutations with regard to protein coding regions. According to the new experimental results the independence assumption generally holds, but there are certain exceptions. In particular, the coding regions that represent two adjacent amino acids seem to change in ways that sometimes deviate significantly from the expected theoretical probability under the independence assumption.

A Computational Model Of The Spread Of Ancient Human Populations Based On Mitochondrial Dna Samples, Peter Revesz

CSE Conference and Workshop Papers

The extraction of mitochondrial DNA (mtDNA) from ancient human population samples provides important data for the reconstruction of population influences, spread and evolution from the Neolithic to the present. This paper presents a mtDNA-based similarity measure between pairs of human populations and a computational model for the evolution of human populations. In a computational experiment, the paper studies the mtDNA information from five Neolithic and Bronze Age populations, namely the Andronovo, the Bell Beaker, the Minoan, the Rössen and the Únětice populations. In the past these populations were identified as separate cultural groups based on geographic location, age and the …

An Incremental Phylogenetic Tree Algorithm Based On Repeated Insertions Of Species, Peter Revesz, Zhiqiang Li

CSE Conference and Workshop Papers

In this paper, we introduce a new phylogenetic tree algorithm that generates phylogenetic trees by repeatedly inserting species one-by-one. The incremental phylogenetic tree algorithm can work on proteins or DNA sequences. Computer experiments show that the new algorithm is better than the commonly used UPGMA and Neighbor Joining algorithms.

A Gene-Based Association Method For Mapping Traits Using Reference Transcriptome Data, Eric R. Gamazon, Heather Wheeler, Kaanan P. Shah, Sahar V. Mozaffari, Keston Aquino-Michaels, Robert J. Carroll, Anne E. Eyler, Joshua C. Denny, Gtex Consortium, Dan L. Nicolae, Nancy J. Cox, Hae Kyung Im

Bioinformatics Faculty Publications

Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual’s genetic profile and correlates ‘imputed’ gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys …

Population Genetic Structure Of The Dwarf Seahorse (Hippocampus Zosterae) In Florida, Nathan Fedrizzi, Melanie L. J. Stiassny, J. T. Boehm, Eric R. Dougherty, George Amato, Martin Mendez

Publications and Research

The dwarf seahorse (Hippocampus zosterae) is widely distributed throughout near-shore habitats of the Gulf of Mexico and is of commercial significance in Florida, where it is harvested for the aquarium and curio trades. Despite its regional importance, the genetic structure of dwarf seahorse populations remains largely unknown. As an aid to ongoing conservation efforts, we employed three commonly applied mtDNA markers (ND4, DLoop and CO1) to investigate the genetic structuring of H. zosterae in Florida using samples collected throughout its range in the state. A total of 1450 bp provided sufficient resolution to delineate four populations of dwarf seahorses, as …

Isquest: Finding Insertion Sequences In Prokaryotic Sequence Fragment Data, Abhishek Biswas, David T. Gauthier, Desh Ranjan, Mohammad Zubair

Computer Science Faculty Publications

Motivation: Insertion sequences (ISs) are transposable elements present in most bacterial and archaeal genomes that play an important role in genomic evolution. The increasing availability of sequenced prokaryotic genomes offers the opportunity to study ISs comprehensively, but development of efficient and accurate tools is required for discovery and annotation. Additionally, prokaryotic genomes are frequently deposited as incomplete, or draft stage because of the substantial cost and effort required to finish genome assembly projects. Development of methods to identify IS directly from raw sequence reads or draft genomes are therefore desirable. Software tools such as Optimized Annotation System for Insertion Sequences …

Bioinformatic Game Theory And Its Application To Cluster Multi-Domain Proteins, Brittney Keel

Department of Mathematics: Dissertations, Theses, and Student Research

The exact evolutionary history of any set of biological sequences is unknown, and all phylogenetic reconstructions are approximations. The problem becomes harder when one must consider a mix of vertical and lateral phylogenetic signals. In this dissertation we propose a game-theoretic approach to clustering biological sequences and analyzing their evolutionary histories. In this context we use the term evolution as a broad descriptor for the entire set of mechanisms driving the inherited characteristics of a population. The key assumption in our development is that evolution tries to accommodate the competing forces of selection, of which the conservation force seeks to …

Heterogeneous Dynamics In Dna Site Discrimination By The Structurally Homologous Dna-Binding Domains Of Ets-Family Transcription Factors, Gaofei He, Ana Tolic, James Bashkin, Gregory Poon

Chemistry & Biochemistry Faculty Works

The ETS family of transcription factors exemplifies current uncertainty in how eukaryotic genetic regulators with overlapping DNA sequence preferences achieve target site specificity. PU.1 and Ets-1 represent archetypes for studying site discrimination by ETS proteins because their DNA-binding domains are the most divergent in sequence, yet they share remarkably superimposable DNA-bound structures. To gain insight into the contrasting thermodynamics and kinetics of DNA recognition by these two proteins, we investigated the structure and dynamics of site discrimination by their DNA-binding domains. Electrophoretic mobilities of complexes formed by the two homologs with circularly permuted binding sites showed significant dynamic differences only …

Evaluation Of Some Statistical Methods For The Identification Of Differentially Expressed Genes, Andrew L. Haddon

FIU Electronic Theses and Dissertations

Microarray platforms have been around for many years and while there is a rise of new technologies in laboratories, microarrays are still prevalent. When it comes to the analysis of microarray data to identify differentially expressed (DE) genes, many methods have been proposed and modified for improvement. However, the most popular methods such as Significance Analysis of Microarrays (SAM), samroc, fold change, and rank product are far from perfect. When it comes down to choosing which method is most powerful, it comes down to the characteristics of the sample and distribution of the gene expressions. The most practiced method is …

The Effect Of Sample And Sample Matrix On Dna Processing: Mechanisms For The Detection And Management Of Inhibition In Forensic Samples, Lilliana I. Moreno

FIU Electronic Theses and Dissertations

The presence of inhibitory substances in biological forensic samples has, and continues to affect the quality of the data generated following DNA typing processes. Although the chemistries used during the procedures have been enhanced to mitigate the effects of these deleterious compounds, some challenges remain. Inhibitors can be components of the samples, the substrate where samples were deposited or chemical(s) associated to the DNA purification step. Therefore, a thorough understanding of the extraction processes and their ability to handle the various types of inhibitory substances can help define the best analytical processing for any given sample. A series of experiments …

Dynamics Of Marine Bacterial Community Diversity Of The Coastal Waters Of The Reefs, Inlets, And Wastewater Outfalls Of Southeast Florida, Alexandra Mandina Campbell, Jay Fleisher, Christopher D. Sinigalliano, James R. White, Jose V. Lopez

Marine & Environmental Sciences Faculty Articles

Coastal waters adjacent to populated southeast Florida possess different habitats (reefs, oceanic inlets, sewage outfalls) that may affect the composition of their inherent microbiomes. To determine variation according to site, season, and depth, over the course of 1 year, we characterized the bacterioplankton communities within 38 nearshore seawater samples derived from the Florida Area Coastal Environment (FACE) water quality survey. Six distinct coastal locales were profiled – the Port Everglades and Hillsboro Inlets, Hollywood and Broward wastewater outfalls, and associated reef sites using culture-independent, high-throughput pyrosequencing of the 16S rRNA V4 region. More than 227,000 sequences helped describe longitudinal taxonomic …

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 …

Modeling Neurovascular Coupling From Clustered Parameter Sets For Multimodal Eeg-Nirs, M. Tanveer Talukdar, H. Robert Frost, Solomon G. G. Diamond

Dartmouth Scholarship

Despite significant improvements in neuroimaging technologies and analysis methods, the fundamental relationship between local changes in cerebral hemodynamics and the underlying neural activity remains largely unknown. In this study, a data driven approach is proposed for modeling this neurovascular coupling relationship from simultaneously acquired electroencephalographic (EEG) and near-infrared spectroscopic (NIRS) data. The approach uses gamma transfer functions to map EEG spectral envelopes that reflect time-varying power variations in neural rhythms to hemodynamics measured with NIRS during median nerve stimulation. The approach is evaluated first with simulated EEG-NIRS data and then by applying the method to experimental EEG-NIRS data measured from …

Hash-Map-Eradicator: Filtering Non-Target Sequences From Next Generation Sequencing Reads, Jonathon Brenner, Catherine Putonti

Bioinformatics Faculty Publications

Contemporary DNA sequencing technologies are continuously increasing throughput at ever decreasing costs. Moreover, due to recent advances in sequencing technology new platforms are emerging. As such computational challenges persist. The average read length possible has taken a giant leap forward with the PacBio and Nanopore solutions. Regardless of the platform used, impurities within the DNA preparation of the sample - be it from unintentional contaminants or pervasive symbiots - remains an issue. We have developed a new tool, HAsh-MaP-ERadicator (HAMPER), for the detection and removal of non-target, contaminating DNA sequences. Integrating hash-based and mapping-based strategies, HAMPER is both memory and …

Sheep Updates 2015 - Ravensthorpe, Bruce Mullan, Kate Pritchett, Kimbal Curtis, Chris Wilcox, Mike Hyder, Leigh Sonnerman, Lynne Bradshaw, Geoff Lindon, Katherine Davies, Joe Young, Stephen Lee, Ian Robertson, Lucy Anderton, Hayley Norman, Ed Barrett-Lenard, Jackie Jarvis, Ben Patrick

Sheep Updates

This session covers fourteen papers from different authors:

1. The Sheep Industry Business Innovation project, Bruce Mullan, Sheep Industry Development Director, Department of Agriculture and Food, Western Australia

2. Western Australian sheep stocktake, Kate Pritchett and Kimbal Curtis, Research Officers, Department of Agriculture and Food, Western Australia

3. Wool demand and supply - short term volatility, long term opportunities, Chris Wilcox, Principal of Poimena Analysis

4. Lifetime management for maternal ewes, Mike Hyder, Research Officer, Department of Agriculture and Food, Western Australia

5. National Livestock Identification System (NLIS) for sheep and goats - what is the NLIS database? Leigh Sonnermann, …