Genetics and Genomics Commons^™

A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe

Department of Biological Sciences Publications

The physical characteristics of bacteriophages establish them as viable candidates for downstream development of pathogen detection assays and biocontrol measures. To utilize phages for such purposes, a detailed knowledge of their host interaction mechanisms is a prerequisite. There is currently a wealth of knowledge available concerning Gram-negative phage-host interaction, but little by comparison for Gram-positive phages and Listeria phages in particular. In this research, the lytic spectrum of two recently isolated Listeria monocytogenes phages (vB_LmoS_188 and vB_LmoS_293) was determined, and the genomic basis for their observed serotype 4b/4e host-specificity was investigated using comparative genomics. The late tail genes of these …

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 …

Genome-Wide Detection And Analysis Of Multifunctional Genes, Yuri Pritykin, Dario Ghersi, Mona Singh

Interdisciplinary Informatics Faculty Publications

Many genes can play a role in multiple biological processes or molecular functions. Identifying multifunctional genes at the genome-wide level and studying their properties can shed light upon the complexity of molecular events that underpin cellular functioning, thereby leading to a better understanding of the functional landscape of the cell. However, to date, genome-wide analysis of multifunctional genes (and the proteins they encode) has been limited. Here we introduce a computational approach that uses known functional annotations to extract genes playing a role in at least two distinct biological processes. We leverage functional genomics data sets for three organisms—H. sapiens, …

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 …

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

School of Computing: 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.

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

School of Computing: 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.

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 …

Functional Characterization Of The Roles Of Endocytic Recycling Regulator Ehd1 Using In Vivo And In Vitro Analyses, Priyanka Arya

Theses & Dissertations

Endocytic recycling is a fundamental cellular process that allows the precise regulation of the membrane components and receptors at the cell surface. Recent studies have established that the C-terminal Eps15 homology domain-containing (EHD) proteins function as key regulators of this process. Four highly-conserved members of the EHD protein family in mammals, EHD1-EHD4, play shared as well as unique roles in endocytic trafficking. Studies presented here demonstrate a critical role of EHD1 in the normal ocular development in mice. Ehd1 knockout mice generated in our laboratory displayed gross ocular phenotypes including the anophthalmia, microphthalmia, and congenital cataracts. Hematoxylin and eosin (H&E) …

A Parallel Algorithm For Compression Of Big Next-Generation Sequencing Datasets, Sandino N. Vargas Perez, Fahad Saeed

Parallel Computing and Data Science Lab Technical Reports

With the advent of high-throughput next-generation sequencing (NGS) techniques, the amount of data being generated represents challenges including storage, analysis and transport of huge datasets. One solution to storage and transmission of data is compression using specialized compression algorithms. However, these specialized algorithms suffer from poor scalability with increasing size of the datasets and best available solutions can take hours to compress gigabytes of data. In this paper we introduce paraDSRC, a parallel implementation of DSRC algorithm using a message passing model that presents reduction of the compression time complexity by a factor of O(1/p ). Our experimental results show …

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 …

Germline Mutation Detection In Next Generation Sequencing Data And Tp53 Mutation Carrier Probability Estimation For Li-Fraumeni Syndrome, Gang Peng

Dissertations and Theses (Open Access)

Next generation sequencing technology has been widely used in genomic analysis, but its application has been compromised by the missing true variants, especially when these variants are rare. We proposed a family-based variant calling method, FamSeq, integrating Mendelian transmission information with de novo mutation and sequencing data to improve the variant calling accuracy. We investigated the factors impacting the improvement of family-based variant calling in simulation data and validated it in real sequencing data. In both simulation and real data, FamSeq works better than the single individual based method.

In FamSeq, we implemented four different methods for the Mendelian genetic …

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 …

Is Trust Always Better Than Distrust? The Potential Value Of Distrust In Newer Virtual Teams Engaged In Short-Term Decision-Making, Paul Benjamin Lowry, Ryan M. Schuetzler, Justin Scott Giboney, Thomas A. Gregory

Information Systems and Quantitative Analysis Faculty Publications

The debate on the benefits of trust or distrust in groups has generated a substantial amount of research that points to the positive aspects of trust in groups, and generally characterizes distrust as a negative group phenomenon. Therefore, many researchers and practitioners assume that trust is inherently good and distrust is inherently bad. However, recent counterintuitive evidence obtained from face-to-face (FtF) groups indicates that the opposite might be true; trust can prove detrimental, and distrust instrumental, to decision-making in groups. By extending this argument to virtual teams (VTs), we examined the value of distrust for VTs completing routine and non-routine …

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 …

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 …

Parallel And Divergent Evolutionary Solutions For The Optimization Of An Engineered Central Metabolism In Methylobacterium Extorquens Am1, Sean Carroll, Lon Chubiz, Deepa Agashe, Christopher Marx

Biology Department Faculty Works

Bioengineering holds great promise to provide fast and efficient biocatalysts for methanol-based biotechnology, but necessitates proven methods to optimize physiology in engineered strains. Here, we highlight experimental evolution as an effective means for optimizing an engineered Methylobacterium extorquens AM1. Replacement of the native formaldehyde oxidation pathway with a functional analog substantially decreased growth in an engineered Methylobacterium, but growth rapidly recovered after six hundred generations of evolution on methanol. We used whole-genome sequencing to identify the basis of adaptation in eight replicate evolved strains, and examined genomic changes in light of other growth and physiological data. We observed great variety …

Creation Of A Computational Pipeline To Extract Genes From Quantitative Trait Loci For Diabetes And Obesity, Joseph Fox

Master's Theses (2009 -)

Type 2 Diabetes is a disease of relative insulin deficiency resulting from a combination of insulin resistance and decreased beta-cell function. Over the past several years, over 60 genes have been identified for Type 2 Diabetes in human genome-wide association studies (GWAS). It is important to understand the genetics involved with Type 2 diabetes in order to improve treatment and understand underlying molecular mechanisms. Heterogeneous stock (HS) rats are derived from 8 inbred founder strains and are powerful tools for genetic studies because they provide a basis for high resolution mapping of quantitative trait loci (QTL) in a relatively short …

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 …

Establishment Of Biotrophy By The Maize Anthracnose Pathogen Colletotrichum Graminicola: Use Of Bioinformatics And Transcriptomics To Address The Potential Roles Of Secretion, Stress Response, And Secreted Proteins, Ester Alvarenga Santos Buiate

Theses and Dissertations--Plant Pathology

Colletotrichum graminicola is a hemibiotrophic pathogen of maize that causes anthracnose leaf and stalk rot diseases. The pathogen penetrates the host and initially establishes an intracellular biotrophic infection, in which the hyphae are separated from the living host cell by a membrane that is elaborated by the host, apparently in response to pathogen signals. A nonpathogenic mutant (MT) of C. graminicola was generated that germinates and penetrates the host normally, but is incapable of establishing a normal biotrophic infection. The mutated gene is Cpr1, conserved in eukaryotes and predicted to encode a component of the signal peptidase complex. How …

Mysteries Of The Trypanosomatid Maxicircles: Characterization Of The Maxicircle Genomes And The Evolution Of Rna Editing In The Order Kinetoplastida, Preethi Ranganathan Iyengar

Theses and Dissertations

The trypanosomatid protists belonging to Order Kinetoplastida are some of the most successful parasites ever known to mankind. Their extreme physiological diversity and adaptability to different environmental conditions and host systems make them some of the most widespread parasites, causing deadly diseases in humans and other vertebrates.

This project focuses on their unique mitochondrion, called the kinetoplast, and more specifically involves the characterization of a part of their mitochondrial DNA (also called kinetoplast DNA or kDNA), the maxicircles, which are functional homologs of eukaryotic mitochondrial DNA in the kinetoplastid protists. We have sequenced and characterized the maxicircle genomes of 20 …

Evolution Of New Duplicate Genes In Arabidopsis Thaliana, Nicholas Curtis Marowsky

Wayne State University Theses

Abstract

Gene duplication is one of the major mechanisms by which organisms expand their genomes. The material added to the genome can then be acted upon by mutation and natural selection to increase the fitness of the species. By studying these duplicate sequences we can understand the process by which species evolve new functional genes. In a previous paper we identified 100 new duplicate genes through a genome wide comparison between A. thaliana and related species. We selected three of these new duplicate genes and investigated more closely their sequence and expression divergence from their parental gene. The three new …

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 …

On The Comparison Of State- And Transition-Based Analysis Of Biological Relevance In Gene Co-Expression Networks, Kathryn Dempsey Cooper, Prasuna Vemuri, Hesham Ali

Interdisciplinary Informatics Faculty Proceedings & Presentations

Traditional correlation network analysis typically involves creating a network using gene expression data and then identifying biologically relevant clusters from that network by enrichment with Gene Ontology or pathway information. When one wants to examine these networks in a dynamic way - such as between controls versus treatment or over time - a "snapshot" approach is taken by comparing network structures at each time point. The biological relevance of these structures are then reported and compared. In this research, we examine the same "snapshot" networks but focus on the enrichment of changes in structure to determine if these results give …

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 …