Computational Biology Commons^™

The Differences Of Prokaryotic Pan-Genome Analysis On Complete Genomes And Simulated Metagenome-Assembled Genomes, Tang Li

Dissertations, Theses, & Student Research in Food Science and Technology

Metagenomic assembly is often used in microbiome research. In metagenomic assembly, contigs are binned based on the shared nucleotide composition. These contig bins are called metagenome-assembled genomes (MAGs), each representing a unique bacterial genome recovered from metagenome sequencing. Hundreds of thousands of high-quality MAGs of various ecological environments have been published since 2017, and increasingly more MAGs are being used in pan-genome analyses where unculturable species or species without reference genomes are studied in microbiome research. However, compared to the traditional pan-genome analysis that uses isolate genomes (from a pure strain isolated from a mixed bacterial population), it is not …

Genomic And Ecological Dimensions Of Malagasy Reptile And Amphibian Biodiversity, Arianna L. Kuhn

Dissertations, Theses, and Capstone Projects

A long history of isolation coupled with complex topographic and ecological landscapes makes Madagascar ideal for exploring the historical factors that have shaped patterns of population diversity and endemism. Many species-level studies have suggested Late Quaternary climate change may have influenced population dynamics in the tropics, but Madagascar’s ecologically unique biomes or individual species properties may have driven idiosyncratic responses to these shifts. Using community-scale population genetic data I implement a hierarchical approximate Bayesian computation (hABC) approach to evaluate the degree of synchronous population expansion during glacial cycles across herpetofaunal assemblages both within and across discrete biomes and taxonomic groups. …

Dynamic Observers For Unknown Populations, Chris Guiver, Nathan Poppelreiter, Richard Rebarber, Brigitte Tenhumberg, Stuart Townley

Brigitte Tenhumberg Papers

Dynamic observers are considered in the context of structuredpopulation modeling and management. Roughly, observers combine a known measured variable of some process with a model of that process to asymptotically reconstruct the unknown state variable of the model. We investigate the potential use of observers for reconstructing population distributions described by density-independent (linear) models and a class of density-dependent (nonlinear) models. In both the density-dependent and -independent cases, we show, in several ecologically reasonable circumstances, that there is a natural, optimal construction of these observers. Further, we describe the robustness these observers exhibit with respect to disturbances and uncertainty in …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

A Tissue Specific Transcriptomic, Proteomic And Phospho-Proteomic Atlas Of The Translational Machinery Of Arabidopsis Thaliana, Abdullah Salim

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Gene expression encompasses the flow of genetic information from DNA to mRNA (transcription) and from mRNA to protein (translation) along with the regulatory mechanisms underlying these processes. Omics technologies offer a powerful toolset with which to study gene expression at each of these stages. A recently published dataset integrating transcriptomic, proteomic and phospho-proteomic measurements from 30 Arabidopsis thaliana tissues provides a unique resource to explore gene expression.¹ The translational machinery (the ribosome, and its initiation, elongation, and termination factors) are a core component in gene expression. Defects in translation can be lethal or lead to major developmental defects and …

Mucin And Splice Variant Profiles Of Pancreatic Adenocarcinoma Predict Patient Survival And Subtyping, Christopher M. Thompson

Theses & Dissertations

PDAC is a pancreatic epithelial malignancy and demonstrates aggressive progression and bleak patient prognosis. Despite decades of research, the evolution of novel diagnostics and intervention modalities for PDAC is stagnant. This dissertation explores the characteristic aberrant and elevated expression of mucins in PDAC. Beginning with the hypothesis that mucins are associated with disease aggressiveness, analysis of PDAC patient survival in TCGA revealed no associations between single mucin expression and patient survival. This led to the underlying issue of PDAC tumor cellularity since this disease demonstrates variability in the proportion of cancer cells within the tumor. Tumor purity assessed with the …

Applications Of Comparative Genomics And Data Science To Agricultural And Clinical Research, Katrina A. Schlum

Doctoral Dissertations

The advent of inexpensive, high-throughput whole genome sequencing (WGS) technologies has led to the generation of thousands of related genomes, even from a single study. Large-scale genome analysis has resulted in hypothesis-generating approaches in the fields of clinical, human and agriculture genomics. Additionally, population-level genomic sampling has resulted in a decrease in false positives in genotype-phenotype associations and an increase in understanding of the basis of disease, antibiotic and pesticide resistance. Deeper understanding of migration, genetic divergence and evolution has also been made possible due to WGS. This research applies comparative genomics, population genomics and data science approaches to whole …

Computational Approaches To Delineate Transcriptional And Functional Heterogeneity In Pancreatic Cancer, Sanjana Srinivasan

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is an incurable disease characterized by poor survival, dense desmoplastic stroma and activating mutations in KRAS (>90%). These tumors are highly complex ecosystems composed of molecularly distinct sub-populations that exhibit a spectrum of genetic features and associated phenotypes. Despite recent advances in the transcriptomic characterization of PDAC into at least two tumor subtypes, this alone has been insufficient to define more specific patterns of oncogenic dependency. To fully leverage advancements in next generation sequencing and functional genomics, we have sought to establish computational methodologies to aid in refined target discovery, and to develop a novel …

Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. Core essential genes are absolutely required for growth and proliferation in every cell type. On the other hand, context-dependent essential genes become essential in an environmental or genetic context. The concept of context-dependent gene essentiality is particularly important in cancer, since killing cancer cells selectively without harming surrounding healthy tissue remains a major challenge. The toxicity of …

Rare Variant Association Studies In Crohn’S Disease And Colorectal Cancer: Methods And Applications, Jiun-Sheng Chen

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Genetic factors account for a substantial portion of Crohn’s disease and colorectal cancer (CRC) risk. Patients with Crohn’s disease, a condition that causes chronic inflammation of the gastrointestinal tract, are at increased risk of colorectal cancer morbidity and mortality. Genome-wide association studies using single marker approaches have identified loci responsible for these diseases, but disease susceptibility from rare variants is incompletely understood. This dissertation includes three chapters, two association studies for Crohn’s disease and CRC, and a statistical method to improve the power of statistical tests.

For Crohn’s disease, we performed targeted sequencing of 101 genes in 205 children with …

Investigating Pirna Expression And Function In Regenerating Tissue Of Segmented Annelid Capitella Teleta, Beatriz Schueng Zancanela

Honors Theses

Regeneration can be observed virtually in all animals and previous studies have identified numerous genes involved in this process. In some invertebrates, the P-element induced wimpy testis (PIWI) genes appear to have an essential role. One such organism is Capitella teleta, a widely accepted model for annelid development. PIWI proteins are associated with small non-coding RNA called PIWI-interacting RNAs or piRNAs, which are involved in transposon silencing in the germline cells of many animals. It was previously believed that these proteins were only expressed in germline cells, however, recent studies have shown expression in somatic tissues as well. The function …

Lotus: A Web-Based Computational Tool For The Preliminary Investigation Of A Novel Mst Method Utilizing A Library Of 16s Rrna Bacteroides Otus, Ginger Dewitte

Master's Theses

Microbial Source Tracking (MST) is a field of study that attempts to identify the source of fecal contamination in waterways in order to assist with development of remediation strategies. Biologists at Cal Poly Center for Applications in Biotechnology (CAB) are developing a new MST method using microbes from the genus Bacteroides. Bacteroides species are host-specific microorganisms that can theoretically be used to trace back to a single host species. After fecal samples are collected, biologists use Next-Generation Sequencing (NGS) techniques to obtain only the genetic sequences of microorganisms belonging to the phylum Bacteroidetes. Investigators hypothesize that similar sequences belong …

A Novel Jumbo Phage Phima05 Inhibits Harmful Microcystis Sp., Ampapan Naknaen, Oramas Suttinun, Komwit Surachat, Eakalak Khan, Rattanaruji Pomwised

Civil & Environmental Engineering and Construction Faculty Publications

Microcystis poses a concern because of its potential contribution to eutrophication and production of microcystins (MCs). Phage treatment has been proposed as a novel biocontrol method for Microcystis. Here, we isolated a lytic cyanophage named PhiMa05 with high efficiency against MCs-producing Microcystis strains. Its burst size was large, with approximately 127 phage particles/infected cell, a short latent period (1 day), and high stability to broad salinity, pH and temperature ranges. The PhiMa05 structure was composed of an icosahedral capsid (100 nm) and tail (120 nm), suggesting that the PhiMa05 belongs to the Myoviridae family. PhiMa05 inhibited both planktonic and aggregated …

Open-Source Computational Framework For Studying Drosophila Behavioral Phase, Boyan Kostadinov, Hannah Lee Pettibone, Evardra Valerie Bell, Xiaona Zhou, Ausra Pranevicius, Orie Thomas Shafer, Maria Paz Fernandez

Publications and Research

This protocol describes a standardized method for analyzing Drosophila behavioral rhythmicity under light dark cycles, temperature ramps, and free running conditions. The protocol constitutes a step-by-step guide from generation of appropriate Drosophila genetic crosses to behavioral experiments. We also provide an opensource computational framework using R for the analysis of the phase of behavior using circular statistics. An extended method for complete use is also provided. For complete details on the use and execution of this protocol, please refer to Fernandez et al. (2020).

Stategra: Multi-Omics Data Integration - A Conceptual Scheme With A Bioinformatics Pipeline, Nuria Planell, Vincenzo Lagani, Patricia Sebastian-Leon, Frans Van Der Kloet, Ewoud Ewing, Nestoras Karathanasis, Arantxa Urdangarin, Imanol Arozarena, Maja Jagodic, Ioannis Tsamardinos, Sonia Tarazona, Ana Conesa, Jesper Tegner, David Gomez-Cabrero

Computational Medicine Center Faculty Papers

Technologies for profiling samples using different omics platforms have been at the forefront since the human genome project. Large-scale multi-omics data hold the promise of deciphering different regulatory layers. Yet, while there is a myriad of bioinformatics tools, each multi-omics analysis appears to start from scratch with an arbitrary decision over which tools to use and how to combine them. Therefore, it is an unmet need to conceptualize how to integrate such data and implement and validate pipelines in different cases. We have designed a conceptual framework (STATegra), aiming it to be as generic as possible for multi-omics analysis, combining …

Insights Into Leptopilina Spp. Immune-Suppressive Strategies Using Mixed-Omics And Molecular Approaches, Brian Wey

Dissertations, Theses, and Capstone Projects

Host-parasite interactions influence the biology of each over the course of evolution. Parasite success allows for the passage of potent virulence strategies from generation to generation. Host success passes stronger immunity and resistance strategies to the following generations as well. Only by studying both partners within their natural contexts can we begin to understand the relationship between the two and how immune mechanisms and virulence strategies interact as a molecular arms race.

In this work, we focus on a natural host-parasite pair, the Drosophila-Leptopilina model. Leptopilina species are parasites of several fruit fly species, including Drosophila melanogaster. This model …

Understanding And Exploiting Protein Allostery And Dynamics Using Molecular Simulations, Sukrit Singh

Arts & Sciences Electronic Theses and Dissertations

Protein conformational landscapes contain much of the functionally relevant information that is useful for understanding biological processes at the chemical scale. Understanding and mapping out these conformational landscapescan provide valuable insight into protein behaviors and biological phenomena, and has relevance to the process of therapeutic design.

While structural biology methods have been transformative in studying protein dynamics, they are limited by technicallimitations and have inherent resolution limits. Molecular dynamics (MD) simulations are a powerful tool for exploring conformational landscapes, and provide atomic-scale information that is useful in understanding protein behaviors. With recent advances in generating datasets of large timescale simulations …

Distribution And Diversity Of Heliothine And Other Lepidopteran Nudiviruses, Emrah Ozel

Theses and Dissertations--Entomology

Helicoverpa zea nudivirus 2 (HzNV-2) is the only known sterilizing and sexually-transmitted insect virus and causes pathological symptoms in H. zea reproductive tissues. HzNV-2 has features that make it a candidate as a H. zea (corn earworm) control agent, such as the ability to cause asymptomatic (latent) and symptomatic (lytic) infections and the ability to influence mating behavior of its host to favor virus spread. HzNV pathology has been studied and its genome sequenced, however, its prevalence in natural populations is largely unknown. In this study, we developed and used a low-cost PCR-based molecular survey to investigate HzNV-2 prevalence and …

Leveraging Chemical And Computational Biology To Probe The Cellulose Synthase Complex, B. Kirtley Amos

Theses and Dissertations--Plant and Soil Sciences

Cellular expansion in plants is a complex process driven by the constraint of internal cellular turgor pressure by an expansible cell wall. The main structural element of the cell wall is cellulose. Cellulose is vital to plant fitness and the protein complex that creates it is an excellent target for small molecule inhibition to create herbicides. In the following thesis many small molecules (SMs) from a diverse library were screened in search of new cellulose biosynthesis inhibitors (CBI). Loss of cellular expansion was the primary phenotype used to search for putative CBIs. As such, this was approached in a forward …

Molecular Mechanisms Regulating Optic Fissure Fusion During Zebrafish Eye Development, Megan Weaver

Theses and Dissertations--Biology

Vertebrate retinal development requires timely and precise fusion of the optic fissure. Failure of this event leads to congenital vision impairment in the form of coloboma. Recent studies have suggested hyaloid vasculature to be involved in OF fusion. In order to examine this link, we analyzed optic fissure fusion and hyaloid vasculogenesis in the zebrafish pax2a noi mutant line. We first determined that pax2a^-/- embryos fail to accumulate F-actin in the optic fissure prior to basement membrane (BM) degradation. Furthermore, using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a^-/- embryos. When examining the connection …