Bioinformatics Commons^™

Identifying Glioblastoma Gene Networks Based On Hypergeometric Test Analysis, Vasileios Stathias, Chiara Pastori, Tess Z. Griffin, Ricardo Komotar, Jennifer L. Clarke, Ming Zhang, Nagi G. Ayad

Department of Statistics: Faculty Publications

Patient specific therapy is emerging as an important possibility for many cancer patients. However, to identify such therapies it is essential to determine the genomic and transcriptional alterations present in one tumor relative to control samples. This presents a challenge since use of a single sample precludes many standard statistical analysis techniques. We reasoned that one means of addressing this issue is by comparing transcriptional changes in one tumor with those observed in a large cohort of patients analyzed by The Cancer Genome Atlas (TCGA). To test this directly, we devised a bioinformatics pipeline to identify differentially expressed genes in …

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA …

Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood

Doctoral Dissertations

Microbial chemotaxis receptors (chemoreceptors) are complex proteins that sense the external environment and signal for flagella-mediated motility, serving as the GPS of the cell. In order to sense a myriad of physicochemical signals and adapt to diverse environmental niches, sensory regions of chemoreceptors are frenetically duplicated, mutated, or lost. Conversely, the chemoreceptor signaling region is a highly conserved protein domain. Extreme conservation of this domain is necessary because it determines very specific helical secondary, tertiary, and quaternary structures of the protein while simultaneously choreographing a network of interactions with the adaptor protein CheW and the histidine kinase CheA. This dichotomous …

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 …

Tal Effector-Nucleotide Targeter (Tale-Nt) 2.0: Tools For Tal Effector Design And Target Prediction, Erin L. Doyle, Nicholas J. Booher, Daniel S. Standage, Daniel F. Voytas, Volker P. Brendel, John K. Vandyk, Adam J. Bogdanove

John K. VanDyk

Transcription activator-like (TAL) effectors are repeat-containing proteins used by plant pathogenic bacteria to manipulate host gene expression. Repeats are polymorphic and individually specify single nucleotides in the DNA target, with some degeneracy. A TAL effector-nucleotide binding code that links repeat type to specified nucleotide enables prediction of genomic binding sites for TAL effectors and customization of TAL effectors for use in DNA targeting, in particular as custom transcription factors for engineered gene regulation and as site-specific nucleases for genome editing. We have developed a suite of web-based tools called TAL Effector-Nucleotide Targeter 2.0 (TALE-NT 2.0;https://boglab.plp.iastate.edu/) that enables design of custom …

Investigating The Role Of Micrornas In The Response To Nitrogen Deprivation In The Green Alga Chlamydomonas Reinhardtii, Adam Voshall

School of Biological Sciences: Dissertations, Theses, and Student Research

Microalgae are gaining attention as a potential feedstock for the production of biodiesel, mainly derived from triacylglycerols (TAG). In many algae, TAG synthesis increases dramatically upon certain stresses but this is often accompanied by growth retardation. Rational improvements to strain productivity are limited by the scant knowledge on algal lipid metabolism and gene regulatory mechanisms. In this context, systems-level approaches aimed at understanding and modeling metabolic and regulatory networks may enable hypothesis-driven genetic engineering strategies. The green microalga Chlamydomonas reinhardtii accumulates significant amounts of TAGs under nutrient starvation and provides a genetically tractable model for manipulating biosynthetic pathways. In order …

Identification And Characterization Of Cysteine Protease Genes In Tobacco For Use In Recombinant Protein Production, Kishor Duwadi

Electronic Thesis and Dissertation Repository

Plants are an attractive host system for pharmaceutical protein production. Many therapeutic proteins have been produced and scaled up in plants at a low cost compared to the conventional microbial and animal based systems. The main technical challenge during this process is to produce sufficient level of proteins in plants. Low yield is generally caused by proteolytic degradation during expression and downstream processing of recombinant proteins. The yield of a human therapeutic protein interleukin (IL) -10 produced in transgenic tobacco leaves was found to be below the critical level, and is potentially due to degradation by tobacco cysteine proteases (CysPs). …

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

Dissertations & 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 & 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 …

A Classification And Characterization Of Two-Locus, Pure, Strict, Epistatic Models For Simulation And Detection, Ryan J. Urbanowicz, Ambrose L. S. Granizo-Mackenzie, Jeff Kiralis, Jason H Moore

Dartmouth Scholarship

BackgroundThe statistical genetics phenomenon of epistasis is widely acknowledged to confound disease etiology. In order to evaluate strategies for detecting these complex multi-locus disease associations, simulation studies are required. The development of the GAMETES software for the generation of complex genetic models, has provided the means to randomly generate an architecturally diverse population of epistatic models that are both pure and strict, i.e. all n loci, but no fewer, are predictive of phenotype. Previous theoretical work characterizing complex genetic models has yet to examine pure, strict, epistasis which should be the most challenging to detect. This study addresses three goals: …

The "Progress Clause": An Empirical Analysis Based On The Constitutional Foundation Of Patent Law, Lori Andrews

Lori B. Andrews

An Examination Of The Phylogenetic Diversity Of Green Algae (Chlorophyceae) That Symbiose With Spotted Salamanders (Ambystoma Maculatum) In The Egg Stage., Crystal Xue

Honors Scholar Theses

In 1909, the species Oophila amblystomatis Lambert ex Wille was described for green algae that symbiose with salamanders in the egg stage (Wille). There are two hypotheses about the source of algae: 1) that algae enter from the surrounding water once the egg clutch is laid in a pond, and 2) that they are acquired from the maternal reproductive tract. We developed a third hypothesis developed to account for the salamander reproductive cycle. Male salamanders lay spermatophores, which are protein-filled capsules, on plant matter in and around ponds. Spermatophores are exposed to the environment before use by females in internal …

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 …

Differential Expression Of Cyclin G2, Cyclin Dependent Kinase Inhibitor 2c And Peripheral Myelin Protein 22 Genes During Adipogenesis..Pdf, Jibin Zhang, Yeunsu Suh, Young Min Choi, Jinsoo Ahn, Michael E. Davis, Kichoon Lee

Jibin Zhang

P53 Maintains Hepatic Cell Identity During Liver Regeneration, Zeynep Hande Coban Akdemir

Dissertations & Theses (Open Access)

p53 MAINTAINS HEPATIC CELL IDENTITY DURING LIVER REGENERATION

Zeynep Hande Coban Akdemir, B.S.,M.A.

Advisory Professor: Michelle Craig Barton, Ph.D.

p53 is a tumor suppressor that has been well studied in tumor-derived, cultured cells. However, its functions in normal proliferating cells and tissues are generally overlooked. We propose that p53 functions during the G1-S transition can be studied in normal, differentiated cells during surgery-induced liver regeneration. Two-thirds partial hepatectomy (PH) of mouse liver offers a unique model to compare p53 functions in regenerating versus sham (control) cells. My hypothesis is that intersection of global expression analyses (microarray and RNA sequencing) and …

The Association Between The Il-1 Pathway, Isaac C. Wun

Dissertations & Theses (Open Access)

Cutaneous malignant melanoma (CMM) is a potentially lethal malignancy that warrants attention and further research, as it is known to that there is an increasing rate of incidence in theUnited States, and it is also known that exposure to UV light is its most crucial risk factor, and family history of melanoma is also an important risk factor. Melanoma is an aggressive and lethal cancer in humans. There are an estimated new 132,000 melanoma cases annually worldwide, and the trend has doubled in the past 20 years. However, attempts to treat melanoma have encountered considerable resistance and remained ineffective. The …

R-Fap: Rapid Functional Annotation Of Prokaryotes Using Taxon-Specific Pan-Genomes And 10-Mer Peptides, Jordan Matthew Utley

Masters Theses

The growing implementation of next-generation sequencing technologies presents numerous fields with the opportunity to identify bacteria in near real-time. Fields such as counter-terrorism, forensics, medicine, and even microbial ecology are positioned to benefit from such advances and implementation. However, with the ability to rapidly produce high-quality sequence data comes the need to interpret this data as quickly as it is produced. While gene prediction algorithms have kept pace, functional prediction methods have not.

To bypass the need for large-scale queries to multiple databases for each newly-sequenced genome, the project detailed herein seeks to identify the genes shared within a taxonomic …

Evaluating The Impact Of Genotype Errors On Rare Variant Tests Of Association, Kaitlyn Cook, Alejandra Benitez, Casey Fu, Nathan L. Tintle

Faculty Work Comprehensive List

The new class of rare variant tests has usually been evaluated assuming perfect genotype information. In reality, rare variant genotypes may be incorrect, and so rare variant tests should be robust to imperfect data. Errors and uncertainty in SNP genotyping are already known to dramatically impact statistical power for single marker tests on common variants and, in some cases, inflate the type I error rate. Recent results show that uncertainty in genotype calls derived from sequencing reads are dependent on several factors, including read depth, calling algorithm, number of alleles present in the sample, and the frequency at which an …

Jmu 4-Va Grant: Gene Expression Analysis In The Developing Vertebrate Retina Using Next Generation Sequencing, Raymond A. Enke

Ray Enke Ph.D.

Molblocks: Decomposing Small Molecule Sets And Uncovering Enriched Fragments, Dario Ghersi, Mona Singh

Interdisciplinary Informatics Faculty Publications

The chemical structures of biomolecules, whether naturally occurring or synthetic, are composed of functionally important building blocks. Given a set of small molecules—for example, those known to bind a particular protein—computationally decomposing them into chemically meaningful fragments can help elucidate their functional properties, and may be useful for designing novel compounds with similar properties. Here we introduce molBLOCKS, a suite of programs for breaking down sets of small molecules into fragments according to a predefined set of chemical rules, clustering the resulting fragments, and uncovering statistically enriched fragments. Among other applications, our software should be a great aid in large-scale …

Integrated Assessment Of Predicted Mhc Binding And Cross-Conservation With Self Reveals Patterns Of Viral Camouflage, Lu He, Anne S. De Groot, Andres H. Gutierrez, William D. Martin, Lenny Moise, Chris Bailey-Kellogg

Dartmouth Scholarship

Immune recognition of foreign proteins by T cells hinges on the formation of a ternary complex sandwiching a constituent peptide of the protein between a major histocompatibility complex (MHC) molecule and a T cell receptor (TCR). Viruses have evolved means of "camouflaging" themselves, avoiding immune recognition by reducing the MHC and/or TCR binding of their constituent peptides. Computer-driven T cell epitope mapping tools have been used to evaluate the degree to which articular viruses have used this means of avoiding immune response, but most such analyses focus on MHC-facing ‘agretopes'. Here we set out a new means of evaluating the …

Jibin Zhang's Ppt For Midwest Meeting.Pdf, Jibin Zhang, Yeunsu Suh, Young Min Choi, Michael E. Davis, Kichoon Lee

Jibin Zhang

Computational Model For Survey And Trend Analysis Of Patients With Endometriosis : A Decision Aid Tool For Ebm, Salvo Reina, Vito Reina, Franco Ameglio, Mauro Costa, Alessandro Fasciani

COBRA Preprint Series

Endometriosis is increasingly collecting worldwide attention due to its medical complexity and social impact. The European community has identified this as a “social disease”. A large amount of information comes from scientists, yet several aspects of this pathology and staging criteria need to be clearly defined on a suitable number of individuals. In fact, available studies on endometriosis are not easily comparable due to a lack of standardized criteria to collect patients’ informations and scarce definitions of symptoms. Currently, only retrospective surgical stadiation is used to measure pathology intensity, while the Evidence Based Medicine (EBM) requires shareable methods and correct …

A Comprehensive Microrna Expression Profile Of The Backfat Tissue From Castrated And Intact Full-Sib Pair Male Pigs.Pdf, Ying Bai, Jinming Huang, Gang Liu, Jibin Zhang, Jianying Wang, Chengkun Liu, Meiying Fang

Jibin Zhang

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 …

The Atp2c2 Gene As Transcribed From A Novel Transcriptional Start Site In Pancreatic Acinar Cells, Caitlin M. Sullivan

Electronic Thesis and Dissertation Repository

Strict regulation of cytosolic Ca²⁺ is essential to regulated exocytosis and proper pancreatic acinar cell function, controlled in part by pumps that shuttle Ca²⁺ out of the cytosol. Our laboratory identified a novel isoform of Secretory Ca²⁺ ATPase 2 (SPCA2) containing only the carboxy terminus. Pancreatic SPCA2, is an approximately 17-20 kDa, protein encoded by the Atp2c2 gene and is completely absent in Mist1^-/- acini.. The focus of this thesis was to understand transcriptional regulation of Atp2c2 in the pancreas. Pancreatic Atp2c2 appears to be transcribed from an alternative transcriptional start site (TSS) and is regulated …

A Course-Based Research Experience: How Benefits Change With Increased Investment In Instructional Time, Christopher D. Shaffer, Consuelo J. Alvarez, April E. Bednarski, David Dunbar, Anya L. Goodman, Catherine Reinke, Anne G. Rosenwald, Michael J. Wolyniak, Cheryl Bailey, Daron Barnard, Christopher Bazinet, Dale L. Beach, James E.J. Bedard, Satish Bhalla, John Braverman, Martin Burg, Vidya Chandrasekaran, Hui-Min Chung, Kari Clase, Randall J. Dejong, Justin R. Diangelo, Chunguang Du, Todd T. Eckdahl, Heather Eisler, Julia A. Emerson, Amy Frary, Donald Frohlich, Yuying Gosser, Shubha Govind, Adam Haberman, Amy T. Hark, Charles Hauser, Arlene Hoogewerf, Laura L.M. Hoopes, Carina E. Howell, Diana Johnson, Christopher J. Jones, Lisa Kadlec, Marian Kaehler, S. Catherine Silver Key, Adam Kleinschmit, Nighat P. Kokan, Olga Kopp, Gary Kuleck, Judith Leatherman, Jane Lopilato, Christy Mackinnon, Juan Carlos Martinez-Cruzado, Gerard Mcneil, Stephanie Mel, Hemlata Mistry, Alexis Nagengast, Paul Overvoorde, Don W. Paetkau, Susan Parrish, Celeste N. Peterson, Mary Preuss, Laura K. Reed, Dennis Revie, Srebrenka Robic, Jennifer Roecklein-Canfield, Michael R. Rubin, Kenneth Saville, Stephanie Schroeder, Karim Sharif, Mary Shaw, Gary Skuse, Christopher D. Smith, Mary A. Smith, Sheryl T. Smith, Eric Spana, Mary Spratt, Aparna Sreenivasan, Joyce Stamm, Paul Szauter, Jeffrey S. Thompson, Matthew Wawersik, James Youngblom, Leming Zhou, Elaine R. Mardis, Jeremy Buhler, Wilson Leung, David Lopatto, Sarah C.R. Elgin

Faculty Publications

There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge. We have developed a bioinformatics project that provides a course-based research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant …

Using Phylogenetically-Informed Annotation (Pia) To Search For Light-Interacting Genes In Transcriptomes From Non-Model Organisms, Daniel I. Speiser, M. Sabrina Pankey, Alexander K. Zaharoff, Barbara A. Battelle, Heather D. Bracken-Grissom, Jesse W. Breinholt, Seth M. Bybee, Thomas W. Cronin, Anders Garm, Annie R. Lindgren, Nipam H. Patel, Megan L. Porter, Meredith E. Protas, Anja S. Rivera, Jeanne M. Serb, Kirk S. Zigler, Keith A. Crandall, Todd H. Oakley

Collected Faculty and Staff Scholarship

Background: Tools for high throughput sequencing and de novo assembly make the analysis of transcriptomes (i.e. the suite of genes expressed in a tissue) feasible for almost any organism. Yet a challenge for biologists is that it can be difficult to assign identities to gene sequences, especially from non-model organisms. Phylogenetic analyses are one useful method for assigning identities to these sequences, but such methods tend to be time-consuming because of the need to re-calculate trees for every gene of interest and each time a new data set is analyzed. In response, we employed existing tools for phylogenetic analysis to …

Pitfalls Of Ascertainment Biases In Genome Annotations—Computing Comparable Protein Domain Distributions In Eukarya, Arli A. Parikesit, Lydia Steiner, Peter F. Stadler, Sonja J. Prohaska

Arli A Parikesit

Most investigations into the large-scale patterns of protein evolution are based on gene annotations that have been compiled in reference databases. The use of these resources for quantitative comparisons, however, is complicated by sometimes vast differences in coverage. More importantly, however, we also observe substantial ascertainment biases that cannot be removed by simple normalization procedures. A striking example is provided by the correlations between protein domains. We observe that statistics derived from different computational gene annotation procedure show dramatic discrepancies, and even qualitative changes from negative to positive correlation, when compared to statistics obtained from annotation databases.

Comparative Genomics Of Closely Related Salmonella Enterica Serovar Typhi Strains Reveals Genome Dynamics And The Acquisition Of Novel Pathogenic Elements, Kien-Pong Yap

Kien-Pong Yap

Background Typhoid fever is an infectious disease of global importance that is caused by Salmonella enterica subsp. enterica serovar Typhi (S. Typhi). This disease causes an estimated 200,000 deaths per year and remains a serious global health threat. S. Typhi is strictly a human pathogen, and some recovered individuals become long-term carriers who continue to shed the bacteria in their faeces, thus becoming main reservoirs of infection.

Results A comparative genomics analysis combined with a phylogenomic analysis revealed that the strains from the outbreak and carrier were closely related with microvariations and possibly derived from a common ancestor. Additionally, the …