Genetics and Genomics Commons^™

Development Of An In Silico Kir Genotyping Algorithm And Its Application To Population And Cancer Immunogenetic Analyses, Howard Rosoff

Dissertations and Theses (Open Access)

Gene content determination and variant calling in the complex KIR genomic region are useful for immune system function analysis, pathogenesis and disease risk factor elucidation, immunotherapy development, evolutionary investigations, and human migration modeling. Sequence-specific oligonucleotide and sequence-specific primer PCR methods are the de facto standards for KIR presence/absence identification, but the current platforms are unsuitable for SNP calling, impractical for KIR typing large cohorts of DNA samples, and inapplicable for typing repositories in which sequence data, but not cells or cell analytes, are available. Alternative typing methods, such as in silico sequence-based typing, can address the problems associated with amplicon-based …

Ten Simple Rules For Taking Advantage Of Git And Github, Yasset Perez-Riverol, Laurent Gatto, Rui Wang, Timo Sachsenberg, Julian Uszkoreit, Felipe Da Veiga Leprevost, Christian Fufezan, Tobias Ternent, Stephen J. Eglen, Daniel S. Katz, Tom J. Pollard, Alexander Konovalov, Robert M. Flight, Kai Blin, Juan Antonio Vizcaíno

Molecular and Cellular Biochemistry Faculty Publications

No abstract provided.

An Informatics Research Agenda To Support Precision Medicine: Seven Key Areas., Jessica D Tenenbaum, Paul Avillach, Marge Benham-Hutchins, Matthew K Breitenstein, Erin L Crowgey, Mark A Hoffman, Xia Jiang, Subha Madhavan, John E Mattison, Radhakrishnan Nagarajan, Bisakha Ray, Dmitriy Shin, Shyam Visweswaran, Zhongming Zhao, Robert R Freimuth

Manuscripts, Articles, Book Chapters and Other Papers

The recent announcement of the Precision Medicine Initiative by President Obama has brought precision medicine (PM) to the forefront for healthcare providers, researchers, regulators, innovators, and funders alike. As technologies continue to evolve and datasets grow in magnitude, a strong computational infrastructure will be essential to realize PM's vision of improved healthcare derived from personal data. In addition, informatics research and innovation affords a tremendous opportunity to drive the science underlying PM. The informatics community must lead the development of technologies and methodologies that will increase the discovery and application of biomedical knowledge through close collaboration between researchers, clinicians, and …

Selfish Mutations: The Genetic Basis Of The Paternal Age Effect, Eoin C. Whelan

Biological Sciences Theses & Dissertations

As the mean age of childrearing grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father but have a deleterious effect in offspring.

I present a mathematical model to analyse the normal function of the stem cell compartment, which provides a framework for SSC renewal and accommodates differences between animal systems. In order to model the SSC mutation accumulation, a Markov chain …

Identification, Characterization, And Life Cycle Of Intein-Associated Homing Endonucleases, Joshua J. Skydel

Honors Scholar Theses

Inteins are molecular parasites that have been identified in unicellular organisms from the three domains of life. The intein self-excises following translation of the host gene, and therefore incurs a fitness cost for its carrier. The symbiotic state of the intein to its host is dependent on the presence or absence of a homing endonuclease domain, which facilitates horizontal transfer of the molecule. Identification of this domain provides information on the evolutionary history of the intein, as well as patterns of horizontal gene transfer in microbial communities. I have therefore developed Hidden Markov Models (HMMs) to identify homing endonuclease domains …

Effects Of Mutating The Mrub_1345 Gene Found In Meiothermus Ruber, Brandon M. Wills, Lori R. Scott

Celebration of Learning

Meiothermus ruber is a unique, red-pigmented, thermophilic bacterium that preferentially grows in high-temperature environments ranging from 35-70°C. Due to the lack of studies performed on this organism, there is quite a bit of information missing in regard to the genes found within this organism’s genome and their function. This study focuses in on the Mrub_1345 gene in M. ruber, which has been suggested to be orthologous to the proC gene found of E. coli proline biosynthesis pathway. To test if these genes are orthologs, we performed the complementation assay on wild-type proC. Next, we performed site-directed mutagenesis on amino acids …

Using Hadoop To Identify False Positives In Bacterial Strain Typing From Dna Fingerprints, Colin C. Adams

Computer Science and Software Engineering

Pyroprinting is a novel technique used by the Department of Biological Sciences to obtain “fingerprints” from the DNA of E. coli isolates in order to categorize them into strains. To determine the number of false positives that occur in the pyroprinting process, isolates with the same pyroprints needed to be sequenced to see if their underlying alleles match. If they do match, this shows they are indeed the same strain and are a true positive. If the alleles don’t match, they are different strains and are a false positive. To do this 100 isolates with nucleotide identifiers were sequenced. Over …

Phylogenetic Analysis Of Human Cytomegalovirus Pus27 And Pus28: Ascertaining An Independent Or Linked Evolutionary History, Jessica A. Scarborough

Undergraduate Honors Theses

Human cytomegalovirus (HCMV) is a widespread pathogen that is particularly skilled at evading immune detection and defense mechanisms, largely due to extensive co-evolution with its host’s immune system. One aspect of this co-evolution involves the acquisition of four virally encoded GPCR chemokine receptor homologs, products of the US27, US28, UL33 and UL78 genes. G protein-coupled receptors (GPCR) are the largest family of cell surface proteins, found in organisms from yeast to humans. In this research, phylogenetic analysis was used to investigate the origins of the US27 and US28 genes, which are adjacent in the viral genome. The results indicate that …

Tropical Trees As Islands: Diversity Accumulation Of Armored Scale Insects (Hemiptera: Diaspididae) On Trees As A Function Of Forest Age, Hannah Shapiro

Undergraduate Honors Theses

Armored scale insects (Hemiptera: Diaspididae) are some of the most invasive insects in the world. These cryptic plant parasites are most often encountered in managed agricultural ecosystems, but very little is known about their distribution, abundance, and diversity in tropical rainforest canopies, where they are likely to have their highest diversity. Because these ubiquitous insects are extreme generalists with undirected dispersal, their diversity (alpha and beta) accumulation can conceivably be modeled according to tenets derived from island biogeography theory. For example, one expectation is that older established trees should boast a higher species diversity and abundance than younger ones. Other …

Investigation Of A Mycobacteriophage Transcription Repressor, Kathryn Orban

Honors Thesis

Mycobacteriophage HelDan is a lysogenic, or temperate, phage (virus) of the bacterium Mycobacterium smegmatis, which is a fast-growing, close relative of Mycobacterium tuberculosis, the causative agent of tuberculosis. The phage replication cycle is dependent on time-coordinated gene expression events. In order to study the regulation of gene expression during phage replication, HelDan protein gp73, a putative transcriptional repressor, was studied. Characterization of gp73 structure and function, such as DNA binding activity and affinity, was done using both bioinformatics and biochemical analyses. To this end, the gene encoding gp73 was cloned and the ability of the recombinant gp73 protein …

Next-Generation Sequencing Of A Multi-Drug Resistance Plasmid Captured From Stream Sediment, Kevin G. Libuit

Masters Theses, 2010-2019

Plasmids in agriculturally-impacted bodies of water may play a significant role in the dissemination of antibiotic resistance. Previously, Erika Gehr, as part of her M.S. thesis work in our laboratory, captured environmental plasmids without cultivation of host bacteria from stream sediment into Escherichia coli. Individual plasmids were capable of conferring resistance to a surprising array of antibiotics including aminoglycosides and extended-spectrum β-lactams. In this study, we developed a method to sequence multi-drug resistance plasmids using both Oxford Nanopore MinION and Ion Torrent Personal Genome Machine sequencers. Plasmid pEG1-1 was sequenced on both platforms and a hybrid assembly utilizing data …

Mrub_2874 Is Homologous To B3386 And Mrub_1349 Is Homologous To B2914, But Mrub_1349 Is Not Homologous To B4090, Samantha Murad, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

ABSTRACT. This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_2874 and Mrub_1349. We predict that Mrub_2874 encodes the enzyme ribulose-5-phosphate 3-epimerase (DNA coordinates 2912530..2913204 on the reverse strand), which is the first step of the pentose phosphate pathway (KEGG map number 00030). It catalyzes the conversion of D-ribulose 5-phosphate to D-xylulose 5-phosphate. The E. coli K12 MG1655 ortholog is predicted to be b3386, which has the gene …

Genomic Drivers Of Cutaneous Squamous Cell Carcinoma Development, Vida Chitsazzadeh

Dissertations and Theses (Open Access)

Skin cancer is the most common malignancy in humans. Annually, in U.S. there are over 3 million cases with an estimated overall economic impact of $2 billion. Cutaneous Squamous Cell Carcinoma (cuSCC) comprises 15-20% of all skin cancers. cuSCC has the best-defined progression from a distinct precancerous lesion, the Actinic Keratosis (AK), to invasive cuSCC. Destructive therapies for AK treatment must be used repetitively, causing significant morbidity. There is a tremendous need for targeted diagnostics and therapy for AKs, representing an important opportunity for secondary skin cancer prevention. Our knowledge of the molecular and cellular events that lead to the …

Investigating Metastatic Lineage In Colorectal Cancer By Single Cell Dna Sequencing, Marco Leung

Dissertations and Theses (Open Access)

Metastasis is the primary cause of human cancer deaths. Patients with metastatic colorectal cancer (mCRC) show only an 11% 5-year survival rate, compared to those without local or distant metastases (92% 5-year survival rate). Understanding the CRC tumor evolution may provide valuable insights on how to improve treatment in patients with mCRC. However, the genomic basis of metastasis has been difficult to study, in part due to the extensive intratumor heterogeneity at both the primary and metastatic tumor sites, and the low frequency of subclones with metastatic potential. Previous studies have applied conventional bulk next-generation sequencing (NGS) methods, which have …

Accurate Mutation Annotation And Functional Prediction Enhance The Applicability Of -Omics Data In Precision Medicine, Tenghui Chen

Dissertations and Theses (Open Access)

Clinical sequencing has been recognized as an effective approach for enhancing the accuracy and efficiency of cancer patient management and therefore achieve the goals of personalized therapy. However, the accuracy of large scale sequencing data in clinics has been constrained by many different aspects, such as clinical detection, annotation and interpretation of the variants that are observed in clinical sequencing data. In my Ph.D thesis work, I mainly investigated how to comprehensively and efficiently apply high dimensional -omics data to enhance the capability of precision cancer medicine. Following this motivation, my dissertation has been focused on two important topics in …

Detecting Gene-Gene Interactions Using A Permutation-Based Random Forest Method, Jing Li, James D. Malley, Angeline S. Andrew, Margaret R. Karagas, Jason H. Moore

Dartmouth Scholarship

Identifying gene-gene interactions is essential to understand disease susceptibility and to detect genetic architectures underlying complex diseases. Here, we aimed at developing a permutation-based methodology relying on a machine learning method, random forest (RF), to detect gene-gene interactions. Our approach called permuted random forest (pRF) which identified the top interacting single nucleotide polymorphism (SNP) pairs by estimating how much the power of a random forest classification model is influenced by removing pairwise interactions.

A Mitochondrial Dna-Based Computational Model Of The Spread Of Human Populations, Peter Revesz

School of Computing: Faculty Publications

This paper presents a mitochondrial DNA-based computational model of the spread of human populations. The computation model is based on a new measure of the relatedness of two populations that may be both heterogeneous in terms of their set of mtDNA haplogroups. The measure gives an exponentially increasing weight for the similarity of two haplogroups with the number of levels shared in the mtDNA classification tree. In an experiment, the computational model is applied to the study of the relatedness of seven human populations ranging from the Neolithic through the Bronze Age to the present. The human populations included in …

Fastpop: A Rapid Principal Component Derived Method To Infer Intercontinental Ancestry Using Genetic Data, Yafang Li, Jinyoung Byun, Guoshuai Cai, Xiangjun Xiao, Younghun Han, Olivier Cornelis, James E. Dinulos, Joe Dennis, Douglas Easton, Ivan Gorlov, Michael F. Seldin, Christopher I. Amos

Dartmouth Scholarship

Identifying subpopulations within a study and inferring intercontinental ancestry of the samples are important steps in genome wide association studies. Two software packages are widely used in analysis of substructure: Structure and Eigenstrat. Structure assigns each individual to a population by using a Bayesian method with multiple tuning parameters. It requires considerable computational time when dealing with thousands of samples and lacks the ability to create scores that could be used as covariates. Eigenstrat uses a principal component analysis method to model all sources of sampling variation. However, it does not readily provide information directly relevant to ancestral origin; the …

A Colletotrichum Graminicola Mutant Deficient In The Establishment Of Biotrophy Reveals Early Transcriptional Events In The Maize Anthracnose Disease Interaction, Maria F. Torres, Noushin Ghaffari, Ester A. S. Buiate, Neil Moore, Scott Schwartz, Charles D. Johnson, Lisa J. Vaillancourt

Plant Pathology Faculty Publications

Background: Colletotrichum graminicola is a hemibiotrophic fungal pathogen that causes maize anthracnose disease. It progresses through three recognizable phases of pathogenic development in planta: melanized appressoria on the host surface prior to penetration; biotrophy, characterized by intracellular colonization of living host cells; and necrotrophy, characterized by host cell death and symptom development. A “Mixed Effects” Generalized Linear Model (GLM) was developed and applied to an existing Illumina transcriptome dataset, substantially increasing the statistical power of the analysis of C. graminicola gene expression during infection and colonization. Additionally, the in planta transcriptome of the wild-type was compared with that of …

Phagephisher: A Pipeline For The Discovery Of Covert Viral Sequences In Complex Genomic Datasets, Thomas Hatzopoulos, Siobhan C. Watkins, Catherine Putonti

Bioinformatics Faculty Publications

Obtaining meaningful viral information from large sequencing datasets presents unique challenges distinct from prokaryotic and eukaryotic sequencing efforts. The difficulties surrounding this issue can be ascribed in part to the genomic plasticity of viruses themselves as well as the scarcity of existing information in genomic databases. The open-source software PhagePhisher (http://www.putonti-lab.com/phagephisher) has been designed as a simple pipeline to extract relevant information from complex and mixed datasets, and will improve the examination of bacteriophages, viruses, and virally related sequences, in a range of environments. Key aspects of the software include speed and ease of use; PhagePhisher can be used with …

Bioinformatics Comparison Of M. Ruber Mrub_2507 To E. Coli Pdxk/B1636 And M. Ruber Mrub_2888 To E. Coli Pdxh/B1638 To Determine The Orthologous Nature, Adam Bernardi, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_2507 and Mrub_2888. We predict that Mrub_2507 encodes the enzyme pyridoxal kinase (DNA coordinates 2555521..2556402), which is in the Vitamin B₆ Metabolism pathway (KEGG map number 00750). It catalyzes the conversion of pyridoxine, pyridoxamine, or pyridoxal to pyridoxine 5’-phosphate, pyridoxamine 5’-phosphate, or pyridoxal 5’-phosphate respectively. The E. coli K12 MG1655 ortholog is predicted to be b1636, which has …

Comparing Apples And Oranges?: Next Generation Sequencing And Its Impact On Microbiome Analysis, Adam G. Clooney, Fiona Fouhy, Roy D. Sleator, Aisling O'Driscoll, Stanton Catherine, Paul D. Cotter, Marcus J. Claesson

Department of Biological Sciences Publications

Rapid advancements in sequencing technologies along with falling costs present widespread opportunities for microbiome studies across a vast and diverse array of environments. These impressive technological developments have been accompanied by a considerable growth in the number of methodological variables, including sampling, storage, DNA extraction, primer pairs, sequencing technology, chemistry version, read length, insert size, and analysis pipelines, amongst others. This increase in variability threatens to compromise both the reproducibility and the comparability of studies conducted. Here we perform the first reported study comparing both amplicon and shotgun sequencing for the three leading next-generation sequencing technologies. These were applied to …

Tom Curran, Phd, Frs, Named Executive Director Of Children's Research Institute, Children's Mercy Hospital

Our Story Continues

Tom Curran, PhD, FRS, has been named Chief Scientific Officer and Executive Director of the Children’s Mercy Children’s Research Institute (CRI), effective Feb. 1 [2016]

The Children’s Research Institute at Children’s Mercy Kansas City was established last year to build on the hospital’s century-long history in pediatric research and to focus the hospital’s future research efforts in four key areas:

• Pediatric Genomic Medicine
• Clinical Pharmacology
• Health Services and Outcomes
• Health Care Delivery

Genomic Analysis Of Meiothermus Ruber Mrub_1907 And Meiothermus Ruber Mrub_1844 With Potential Ortholog Escherichia Coli B3774 Ilvc And Escherichia Coli B3771 Ilvc Gene Through Bioinformatics, Felipe A. Hernandez, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_1907 and Mrub_1844. We predict that Mrub__1907 encodes the enzyme ketol-acid reductoisomerase (DNA coordinates 1966630..1967649 on the reverse strand), which is the fourth step of the L-isoleucine pathway (from threonine) (KEGG map number 00290). It catalyzes the conversion of (R)-3- Hydroxy-3-methyl-2-oxopentanoate to (R)-2-3 Dihydroxy-3-methylpentanoate. The E. coli K12 MG1655 ortholog is predicted to be b3774, which has the gene …

Comparison Of Genes In Meiothermus Ruber And Escherichia Coli In The Thiamine Biosynthesis Pathway, Erin E. Frye, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_2046 and Mrub_2041.We predict that Mrub_2046 encodes the enzyme phosphomethylpyrimidine kinase (DNA coordinates 2082772..2083572 on the reverse strand), which is the second step of the Thiamine Metabolism pathway (KEGG map number mrb00730). It catalyzes the conversion of 4-Amino-2-methyl-5-phosphomethylpyrimidine to 4-Amino-2-methyl-5-hydroxymethyl diphosphate The E. coli K12 MG1655 ortholog is predicted to be b2103, which has the gene identifier thiD. We …

Meiothermus Ruber Mrub_0976 And Mrub_1641 Share The Same Functions As Escherichia Coli B3940 And B3433 In The Biosynthesis Of Homoserine, Cody Stephans, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_0976 and Mrub_1641. We predict that Mrub_0976 encodes the enzyme aspartate kinase (DNA coordinates 964404..965630) which is the 1^st step of the homoserine biosynthesispathway (KEGG map number M00018). It catalyzes the conversion L-aspartate to L-asparyl-4-phospate. The E. coli K12 MG1655 ortholog is predicted to be b3940, which has the gene identifier ‘thrA’. We …

Possible Orthologs Of Trpa And Trpb Genes Between E. Coli (B1260 And B1261) And M. Ruber (Mrub_1512 And Mrub_1511), John J. Stenger, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

Mrub_1512 encodes the enzyme tryptophan A (DNA coordinates 1544300..1545091), which is the 6th step of the Tryptophan Biosynthesis pathway (KEGG map number 00400). It catalyzes the conversion of Chorismate to L-Tryptophan. The E. coli K12 MG1655 ortholog is predicted to be b1260, which has the gene identifier trpA. We predict that Mrub_1512 (DNA coordinates 1544300..1545091) is a alpha subunit of the Tryptophan Synthase (KEGG map number 00400). Mrub_1511 encodes the enzyme tryptophan B (DNA coordinates 1543083..1544303), which is the 7th step of the Tryptophan Biosynthesis pathway (KEGG map number 00400). It catalyzes the conversion of Chorismate to L-Tryptophan. The E. …

Mrub_2765 Is The Version Of E. Coli Fabz In Meiothermus Ruber, While Mrub_0266 Is The Version Of E. Coli Fabi In Meiothermus Ruber, Amanda M. Narkis, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_2765 and Mrub_0266. We predict that Mrub_2765 encodes the enzyme β-hydroxyacyl-Acyl carrier protein (ACP) dehydratase (DNA coordinates 2805770..2806213 on the reverse strand), which is the 3^rd step of the fatty acid elongation pathway (KEGG map number 00780). It catalyzes the conversion of (3R)-3-hydroxyacyl-[ACP] to trans-2-enoyl-[ACP]. The E. coli K12 MG1655 ortholog is predicted to be …

Pyruvate Metabolism In M. Ruber When Compared To E. Coli, Amanda M. Johnson, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_0476, Mrub_1516, Mrub_1517, Mrub_0477, and Mrub_2322. We predict that Mrub_0476, Mrub_1516, and Mrub_1517 (DNA coordinates 461643..464366, 1548957..1549955, 1549952..1550986, respectively) are a paralogous a subunit of the pyruvate dehydrogenase complex E1(KEGG map number 00620). We predict that Mrub_0477 and Mrub_2322 (DNA coordinates 464402..465697 and 2371690..2373090, respectively) are a paralogous subunit of the pyruvate dehydrogenase complex …

A Bioinformatics Study On Whether Or Not Mrub_2763 Gene In M. Ruber Is Similar To The Lpxb Gene In E. Coli And If Mrub_2768 Is Similar To The Lpxd Gene In E. Coli., Frank J. Habura, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the gene Mrub_2768 and Mrub_2763. We predict that Mrub_2768 (DNA coordinates 2808186..2809178 on the reverse strand) encodes the enzyme UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase (LpxD), which is the third step of the Lipopolysaccharide biosynthesis pathway (KEGG map number 00540). It catalyzes the conversion of UDP-3-O-(3-hydroxymyristoyl)-α-D-glucosamine + a(3R)-3-hydroxymyristoyl-[acp] → a holo-[acyl-carrier protein] + UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine. The E. coli K12 MG1655 ortholog is predicted to be b0179, which …