Genetics and Genomics 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 …

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. …

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 …

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: …

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 …

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 …

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 …

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 …

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 …

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 …

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 …