Genomics Commons^™

Progress In Pathogen Detection By Whole-Genome Sequencing, Chung Wong

Chemistry & Biochemistry Faculty Works

No abstract provided.

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Power Analysis In Applied Linear Regression For Cell Type-Specific Differential Expression Detection, Edmund Glass

Theses and Dissertations

The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from any tissues suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. However, this variability may actually be advantageous, as heterogeneous gene expression measurements coupled with cell counts may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression. Yet, they do not consider many artifacts hidden in high-dimensional gene expression …

Genomic Comparisons And Genome Architecture Of Divergent Trypanosoma Species, Katie Bradwell

Theses and Dissertations

Virulent Trypanosoma cruzi, and the non-pathogenic Trypanosoma conorhini and Trypanosoma rangeli are protozoan parasites with divergent lifestyles. T. cruzi and T. rangeli are endemic to Latin America, whereas T. conorhini is tropicopolitan. Reduviid bug vectors spread these parasites to mammalian hosts, within which T. rangeli and T. conorhini replicate extracellularly, while T. cruzi has intracellular stages. Firstly, this work compares the genomes of these parasites to understand their differing phenotypes. Secondly, genome architecture of T. cruzi is examined to address the effect of a complex hybridization history, polycistronic transcription, and genome plasticity on this organism, and study its highly …

System Genetic Analysis Of Mechanisms Underlying Excessive Alcohol Consumption, Maren L. Smith

Theses and Dissertations

Increased alcohol consumption over time is one of the characteristic symptoms of Alcohol Use Disorder (AUD). The molecular mechanisms underlying this escalation in intake is still the subject of study. However, the mesocortical and mesolimbic dopamine pathways, and the extended amygdala, because of their involvement in reward and reinforcement are believed to play key roles in these behavioral changes. Multiple gene expression studies have shown that alcohol affects the expression of thousands of genes in the brain. The studies discussed in this document use the systems biology technique of co-expression network analysis to attempt to find

patterns within genome-wide expression …

Population Genetic Structure Of Necturus Maculosus In Central And Eastern Kentucky, Mason Owen Murphy

Theses and Dissertations--Biology

Population structure is influenced by extrinsic factors, such as landscape architecture and dispersal barriers. Lotic network architecture is known to constrain ecological, demographic and evolutionary processes, including population genetic structure. I assessed the population structure of a widespread aquatic salamander, Necturus maculosus, across three river basins in central and eastern Kentucky. I examined the role of network architecture, anthropogenic barriers, and spatial scale on patterns of population structure. I also provided a review of N. maculosus capture methods and offer an improved trap design. I identified significant structuring between the combined Licking/Kinniconick basin and the Kentucky River basin, with …

Resolving Gnetum Evolutionary History, Angela Mcfadden

All Master's Theses

Gnetum are non-flowering seed plants of the tropics, indigenous to South America, Africa, and Asia. This group of about 40 species is fascinating to botanists because it shares distinctive morphological characteristics with flowering plants, such as broad leaves, woody stems, and flower-like strobili. There are still questions surrounding the relationships within the genus of Gnetum. With that in mind, I focused my work on generating phylogenetic hypotheses, using two molecular data sets: a concatenation of over 60 different chloroplast genes (66,815 base pairs), and the whole chloroplast genome (128,772 base pairs). This allowed me to compare the two phylogenies …

Finding Function In The Unknown, Kelly Boyd, Emma Highland, Amanda Misch, Amber Hu, Sushma Reddy, Catherine Putonti

Bioinformatics Faculty Publications

Through high-throughput RNA sequencing (RNAseq), transcriptomes for a single cell, tissue, or organism(s) can be ascertained at a high resolution. While a number of bioinformatic tools have been developed for transcriptome analyses, significant challenges exist for studies of non-model organisms. Without a reference sequence available, raw reads must first be assembled de novo followed by the tedious task of BLAST searches and data mining for functional information. We have created a pipeline, PyRanger, to automate this process. The pipeline includes functionality to assess a single transcriptome and also facilitate comparative transcriptomic studies.

A Survey Of The Common Loon (Gavia Immer) Genome Reveals Patterns Of Natural Selection, Zach G. Gayk

All NMU Master's Theses

With rapid advances in Next-Generation Sequencing technology, comparative genomics has become a viable method for studying the adaptation of species to their environment at the genome level. I investigated this in common loons (Gavia immer)—for which molecular adaptation has not been characterized—by finding signatures of positive selection as evidence for genomic adaptation.

I used Illumina short read sequencing data from a single female common loon to produce a fragmented assembly of the common loon (Gavia immer) genome. The resulting assembly had a contig N50 of 814 bp, a total length of 767,326,331 bp, and 45.7 % …

A Polyglot Approach To Bioinformatics Data Integration: A Phylogenetic Analysis Of Hiv-1, Steven Reisman, Thomas Hatzopoulos, Konstantin Laufer, George K. Thiruvathukal, Catherine Putonti

Bioinformatics Faculty Publications

As sequencing technologies continue to drop in price and increase in throughput, new challenges emerge for the management and accessibility of genomic sequence data. We have developed a pipeline for facilitating the storage, retrieval, and subsequent analysis of molecular data, integrating both sequence and metadata. Taking a polyglot approach involving multiple languages, libraries, and persistence mechanisms, sequence data can be aggregated from publicly available and local repositories. Data are exposed in the form of a RESTful web service, formatted for easy querying, and retrieved for downstream analyses. As a proof of concept, we have developed a resource for annotated HIV-1 …

Bacteriophages Isolated From Lake Michigan Demonstrate Broad Host-Range Across Several Bacterial Phyla, Kema Malki, Alex Kula, Katherine Bruder, Emily Sible, Thomas Hatzopoulos, Stephanie Steidel, Siobhan C. Watkins, Catherine Putonti

Biology: Faculty Publications and Other Works

BACKGROUND:

The study of bacteriophages continues to generate key information about microbial interactions in the environment. Many phenotypic characteristics of bacteriophages cannot be examined by sequencing alone, further highlighting the necessity for isolation and examination of phages from environmental samples. While much of our current knowledge base has been generated by the study of marine phages, freshwater viruses are understudied in comparison. Our group has previously conducted metagenomics-based studies samples collected from Lake Michigan - the data presented in this study relate to four phages that were extracted from the same samples.

FINDINGS:

Four phages were extracted from Lake Michigan …

Obtaining Genomic Sequence Practice, Sarah O'Leary-Driscoll

Introduction to NCBI

No abstract provided.

3: Genomics: Past & Future Bibliography, Sarah O'Leary-Driscoll

Genomics: Past & Future

No abstract provided.

Future Of Genomics: Presentations, Sarah O'Leary-Driscoll

Genomics: Past & Future

In his testimony to a House of Representatives sub-committee on health, director of the National Human Genome Research Institute, Francis S. Collins, said that the future of genomics had three main focal points:

"Genomics to Biology: The human genome sequence provides foundational information that now will allow development of a comprehensive catalog of all of the genome's components, determination of the function of all human genes, and deciphering of how genes and proteins work together in pathways and networks.

Genomics to Health: Completion of the human genome sequence offers a unique opportunity to understand the role of genetic factors in …

K-Mer Analysis On Developmental And Housekeeping Enhancer Peaks, Yunsi Yang, Anurag Sethi, Mark Gerstein

Yale Day of Data

The regulation of gene expression involves interaction between transcriptional enhancers and core promoters. However, the separation between developmental and housekeeping gene regulation remains unknown. Here, we present a method to detect if different core promoters exhibit specificity to certain enhancers within massively parallel assays for enhancer detection. We use k-mers of various length (3-8bp) as sequence features and compare k-mer frequencies between developmental and housekeeping enhancers. This method shows promoter specificity of enhancers in D. melanogaster.

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 …

An Exploration Of The Phylogenetic Placement Of Recently Discovered Ultrasmall Archaeal Lineages, Jeffrey M. O'Brien

Honors Scholar Theses

In recent years, several new clades within the domain Achaea have been discovered. This is due in part to microbiological sampling of novel environments, and the increasing ability to detect and sequence uncultivable organisms through metagenomic analysis. These organisms share certain features, such as small cell size and streamlined genomes. Reduction in genome size can present difficulties to phylogenetic reconstruction programs. Since there is less genetic data to work with, these organisms often have missing genes in concatenated multiple sequence alignments. Evolutionary Biologists have not reached a consensus on the placement of these lineages in the archaeal evolutionary tree. There …

Identification Of Familial Wilms Tumor Predisposition Genes Using Whole Genome Sequencing, Timothy B. Palculict

Dissertations and Theses (Open Access)

Wilms tumor, a childhood tumor arising from undifferentiated renal mesenchyme, is diagnosed in North America at a frequency of 1 in 10,000 live births and accounts for 5% of all pediatric cancers. The etiology of Wilms tumor is heterogeneous with multiple genes known to have an effect on Wilms tumor development; however, these genes are rarely associated with familial Wilms tumor. Gene mutations in WT1, WTX, CTNNB1 and TP53 are observed in a third of sporadic tumors, while the causative gene(s) responsible for familial Wilms tumor are largely unknown. Approximately 2% of Wilms tumor patients have a family …

Detection Of Genes Influencing Chronic And Mendelian Disease Via Loss-Of-Function Variation, Alexander H. Li

Dissertations and Theses (Open Access)

A typical human exome harbors dozens of loss-of-function (LOF) variants predicted to severely disrupt or abolish gene function. These variants are enriched at the extremely rare end of the allele frequency spectrum (< 0.1%), suggesting purifying selection against these sites. However, most previous population-based sequencing studies have not included analysis of genotype-phenotype relationships with LOF variants. Thus, the contribution of LOF variation to health and disease within the general population remains largely uncharacterized.

Using whole exome sequence from 8,554 participants in the Atherosclerosis Risk in Communities (ARIC) study, we explored the impact of LOF variation on a broad spectrum of human phenotypes. First, we selected 20 common chronic disease risk factor phenotypes and performed gene-based association tests. Analysis of this sample verified two relationships in well-studied genes (PCSK9 and APOC3) and identified eight new loci. Novel relationships included …

Addressing The Black Box Phenomenon Of Genome Sequencing And Assembly, Brandon Carter

Senior Honors Projects, 2010-2019

Genomics, a study of all genetic material in an organism, is a new discipline having a great impact on medicine, agriculture, and environmental phenomena. Most undergraduate faculty members were not formally trained in genomics and must retool themselves in order to stay current with these evolving technologies. Advances in sequencing technology have resulted in an explosion of “big data” that can only be managed and analyzed using digital methods. Multiple complex computer programs are required to teach students the concepts using hands-on methods. These programs are challenging to use, especially since the same faculty members lacking genomics training were not …

Characterization Of A Novel Clade Of Transporters In Phytophthora, Stephanie Padula, Paul F. Morris Dr, Howard Casey Cromwell Dr., Menaka Ariyaratne, Andrew Wagner

Honors Projects

The oomycete Phytophthora parasitica has a worldwide distribution and is an economically important pathogen of more than 100 species⁴. RNA-seq analysis showed that one gene, PPTG_16698 has the 5^th highest level of expression of all transport proteins in the zoospore stage, and is highly conserved throughout Phytophthora species. This project attempts to characterize the important biological role that PPTG_16698 plays in P. parasitica and other oomycetes. Three strategies have been implemented to accomplish this goal: growth analysis by heterologous expression in yeast, metabolite analysis in yeast, and construction of a GFP fusion protein to enable localization of …

Developing Microbial Biomarkers To Non-Invasively Assess Health In Wild Elk (Cervus Canadensis) Populations, Samuel B. Pannoni

Undergraduate Theses, Professional Papers, and Capstone Artifacts

The composition of the intestinal bacterial community (intestinal microbiome) of mammals is associated with changes in diet, stress, disease and physical condition of the animal. The relationship between health and the microbiome has been extensively demonstrated in studies of humans and mice; this provides strong support for its potential utility in wildlife. When managing elk (Cervus canadensis), federal and state agencies currently must rely on invasive sampling and coarse demographic data on which to base their decisions. By developing microbiome-based biomarkers that vary as a function of elk body condition and disease (i.e. microbial biomarkers), we hope to …

Novel Computational Methods For Transcript Reconstruction And Quantification Using Rna-Seq Data, Yan Huang

Theses and Dissertations--Computer Science

The advent of RNA-seq technologies provides an unprecedented opportunity to precisely profile the mRNA transcriptome of a specific cell population. It helps reveal the characteristics of the cell under the particular condition such as a disease. It is now possible to discover mRNA transcripts not cataloged in existing database, in addition to assessing the identities and quantities of the known transcripts in a given sample or cell. However, the sequence reads obtained from an RNA-seq experiment is only a short fragment of the original transcript. How to recapitulate the mRNA transcriptome from short RNA-seq reads remains a challenging problem. We …

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 …

Characterization Of The Transcriptome, Nucleotide Sequence Polymorphism, And Natural Selection In The Desert Adapted Mouse Peromyscus Eremicus, Matthew D. Macmanes, Michael B. Eisen

Molecular, Cellular & Biomedical Sciences

As a direct result of intense heat and aridity, deserts are thought to be among the most harsh of environments, particularly for their mammalian inhabitants. Given that osmoregulation can be challenging for these animals, with failure resulting in death, strong selection should be observed on genes related to the maintenance of water and solute balance. One such animal, Peromyscus eremicus, is native to the desert regions of the southwest United States and may live its entire life without oral fluid intake. As a first step toward understanding the genetics that underlie this phenotype, we present a characterization of the …

Advancing The Microbiome Research Community, Curtis Huttenhower, Rob Knight, C. Titus Brown, J. Gregory Caporaso, Jose C. Clemente, Dirk Gevers, Eric A. Franzosa, Scott T. Kelley, Dan Knights, Ruth E. Ley, Anup Mahurkar, Jacques Ravel, Scientists For Advancement Of Microbiome Research, Owen White, Jacques Izard

Department of Food Science and Technology: Faculty Publications

The human microbiome has become a recognized factor in promoting and maintaining health. We outline opportunities in interdisciplinary research, analytical rigor, standardization, and policy development for this relatively new and rapidly developing field. Advances in these aspects of the research community may in turn advance our understanding of human microbiome biology.

It is now widely recognized that disturbances in our normal microbial populations may be linked to acute infections such as Clostridium difficile and to chronic diseases such as heart disease, cancer, obesity, and autoimmune disorders. This has prompted substantial interest in the microbiome from both basic and clinical perspectives. …

Genetic Predictors Of Metabolic Side Effects Of Diuretic Therapy, Jorge L. Del Aguila

Dissertations and Theses (Open Access)

Thiazide diuretics are a recommended first-line monotherapy for hypertension (i.e.SBP>140 mmHg or DBP>90 mmHg). Even so, diuretics are associated with adverse metabolic side effects, such as hyperlipidemia, hyperglycemia and hypokalemia which increase the risk of developing type II diabetes. This thesis used three analytical strategies to identify and quantify genetic factors that contribute to the development of adverse metabolic effects due to thiazide diuretic treatment. I performed a genome-wide association study (GWAS) and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses …

Genomic Characterization Of Polyps In Familial Adenomatous Polyposis Patients And Identification Of Candidate Chemopreventive Drugs, Francis A. San Lucas

Dissertations and Theses (Open Access)

Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by APC germline mutations and the development of hundreds to thousands of premalignant adenomas in the gastrointestinal tract at a young age. If left untreated, these patients inevitably develop colon cancer (CRC) and small bowel tumors. We performed exome sequencing of samples from 12 FAP patients to characterize adenomas and to identify candidate genes of adenoma development that may serve as potential targets for chemoprevention drug development. From each patient, a blood and at least one polyp were sequenced with a total of 25 polyps analyzed. In some cases, normal …

Transcriptome Analysis Of Sea Lamprey Embryogenesis, Zakary Ilya Yermolenko

Seton Hall University Dissertations and Theses (ETDs)

The sea lamprey (Petromyzon marinus) has survived throughout evolution for hundreds of millions of years. It is considered an invasive species to the Great Lakes that has caused dramatic changes in the ecosystem for fish communities resulting in the collapse of a fishing industry that was previously valued at billions of dollars. Successful management of the sea lamprey is essential to a sustainable fishing industry and biodiversity. Therefore sea lamprey embryos were studied at various stages of development by growing them in a simulated habitat. RNAs from adult female ovaries and embryos at different time points during embryogenesis …

Validation Of Predicted Mrna Splicing Mutations Using High-Throughput Transcriptome Data, Coby Viner, Stephanie Dorman, Ben Shirley, Peter Rogan

Biochemistry Publications

Interpretation of variants present in complete genomes or exomes reveals numerous sequence changes, only a fraction of which are likely to be pathogenic. Mutations have been traditionally inferred from allele frequencies and inheritance patterns in such data. Variants predicted to alter mRNA splicing can be validated by manual inspection of transcriptome sequencing data, however this approach is intractable for large datasets. These abnormal mRNA splicing patterns are characterized by reads demonstrating either exon skipping, cryptic splice site use, and high levels of intron inclusion, or combinations of these properties. We present, Veridical, an in silico method for the automatic validation …