Computational Biology Commons^™

Modeling Nonsegmented Negative-Strand Rna Virus (Nnsv) Transcription With Ejective Polymerase Collisions And Biased Diffusion, Felipe-Andres Piedra

Research Symposium

Background: The textbook model of NNSV transcription predicts a gene expression gradient. However, multiple studies show non-gradient gene expression patterns or data inconsistent with a simple gradient. Regarding the latter, several studies show a dramatic decrease in gene expression over the last two genes of the respiratory syncytial virus (RSV) genome (a highly studied NNSV). The textbook model cannot explain these phenomena.

Methods: Computational models of RSV and vesicular stomatitis virus (VSV – another highly studied NNSV) transcription were written in the Python programming language using the Scientific Python Development Environment. The model code is freely available on GitHub: …

An Implementation Of The Method Of Moments On Chemical Systems With Constant And Time-Dependent Rates, Emmanuel O. Adara, Roger B. Sidje

Northeast Journal of Complex Systems (NEJCS)

Among numerical techniques used to facilitate the analysis of biochemical reactions, we can use the method of moments to directly approximate statistics such as the mean numbers of molecules. The method is computationally viable in time and memory, compared to solving the chemical master equation (CME) which is notoriously expensive. In this study, we apply the method of moments to a chemical system with a constant rate representing a vascular endothelial growth factor (VEGF) model, as well as another system with time-dependent propensities representing the susceptible, infected, and recovered (SIR) model with periodic contact rate. We assess the accuracy of …

Computational Analysis Of Antibody Binding Mechanisms To The Omicron Rbd Of Sars-Cov-2 Spike Protein: Identification Of Epitopes And Hotspots For Developing Effective Therapeutic Strategies, Mohammed Alshahrani

Computational and Data Sciences (PhD) Dissertations

The advent of the Omicron strain of SARS-CoV-2 has elicited apprehension regarding its potential influence on the effectiveness of current vaccines and antibody treatments. The present investigation involved the implementation of mutational scanning analyses to examine the impact of Omicron mutations on the binding affinity of four categories of antibodies that target the Omicron receptor binding domain (RBD) of the Spike protein. The study demonstrates that the Omicron variant harbors 23 unique mutations across the RBD regions I, II, III, and IV. Of these mutations, seven are shared between RBD regions I and II, while three are shared among RBD …

Annotation Of Non-Model Species’ Genomes, Taiya Jarva

Master's Theses

The innovations in high throughput sequencing technologies in recent decades has allowed unprecedented examination and characterization of the genetic make-up of both model and non-model species, which has led to a surge in the use of genomics in fields which were previously considered unfeasible. These advances have greatly expanded the realm of possibilities in the fields of ecology and conservation. It is now possible to the identification of large cohorts of genetic markers, including single nucleotide polymorphisms (SNPs) and larger structural variants, as well as signatures of selection and local adaptation. Markers can be used to identify species, define population …

Exploring The Interactions Between Sars-Cov-2 And Host Proteins., Sojan Shrestha

Dissertations and Theses in Biological Sciences

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic, Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is considered to be of zoonotic origin; it originated in non-human animals and was transmitted to humans. Since the early stage of the pandemic, however, the evidence of transmissions from humans to animals (reverse zoonoses) has been found in multiple animal species including mink, white-tailed deer, and pet and zoo animals. Furthermore, secondary zoonotic events of SARS-CoV-2, transmissions from animals to humans, have been also reported. It is suggested that non-human hosts can act as SARS-CoV-2 reservoirs where accumulated …

Exploration Of The Immune Landscape Of Ebv-Associated Gastric Cancers, Mikhail Salnikov

Electronic Thesis and Dissertation Repository

Epstein–Barr virus (EBV) is a gammaherpesvirus associated with 9% of all gastric cancers (GCs). EBV-associated GCs (EBVaGCs) are pathologically and clinically distinct entities from EBV-negative GCs (EBVnGCs), with EBVaGCs exhibiting differential molecular pathology and patient prognosis. The purpose of this thesis is to investigate the tumor microenvironment (TME) of EBVaGCs, which has not been explored in-depth. We hypothesize that EBVaGCs and EBVnGCs are also distinct in terms of the molecular immune landscape. We employed over 400 stomach adenocarcinoma (STAD) samples from The Cancer Genome Atlas (TCGA), as well as a single cell dataset, for the construction of a web suite …

Mining Sars-Cov-2 Phylogenetic Trees To Estimate Circulating Infections And Patterns Of Migration, Erin V. Brintnell

Electronic Thesis and Dissertation Repository

The SARS-CoV-2 pandemic led to the formation of very large databases of genomic viral data. These databases contain information on transmission dynamics, emergence and evolution of SARS-CoV-2. However, extracting this information from sequences is difficult, as most methods of analyzing viral genomes were developed for smaller data sets. Therefore, my objective was to develop new fast estimators of the number of infections (I) and the rate of migration based on simple features of SARS-CoV-2 phylogenies.

I simulated pathogen evolution using a susceptible-exposed-infectious-recovered (SEIR) model of pathogen spread, reconstructing evolution using CoVizu. For simulations of I, I varied the total number …

Pirna Expression In The Tube Feet Of Lytechinus Variegatus, Reagan Milliet

Honors Theses

Tissue regeneration is an area of research with implications for medicine and animal health. While nearly all living multi-cellular organisms are capable of regeneration, there are major differences in the animal kingdom. Some organisms are capable of regenerating virtually every cell in their bodies. In hopes of engineering tissue regeneration for medical applications, the mechanisms by which organisms regenerate are being widely investigated. To better understand regeneration, the role of P-element Induced WImpy testis (PIWI) proteins are being evaluated. In collaboration with PIWIinteracting RNAs (piRNAs), PIWI proteins have been proven instrumental to transposon silencing and maintenance of the genome in …

Acetate Metabolism In The Fungal Pathogen Cryptococcus Neoformans, Oly Ahmed

All Dissertations

Cryptococcus neoformans is an environmental basidiomycetous fungus with a worldwide distribution and a wide range of habitats. Inhalation of the desiccated yeasts or spores of C. neoformans often leads to opportunistic pulmonary infections in immunocompromised individuals, and in severe cases causes lethal meningitis following hematogenous dissemination. During infection, depending on the tissue and disease state, the invading fungi experience a range of nutrient microenvironments within the host body. As a result, rapid metabolic adaptations geared towards efficient utilization of carbon sources alternative to glucose become one of the prime determinants of survival and growth for the pathogen. Incidentally, cryptococcal infection …

Application Of Machine Learning Approaches To Empower Drug Development, Yue Shen

Doctoral Dissertations

Human health, one of the major topics in Life Science, is facing intensified challenges, including cancer, pandemic outbreaks, and antimicrobial resistance. Thus, new medicines with unique advantages, including peptide-based vaccines and permeable small molecule antimicrobials, are in urgent need. However, the drug development process is long, complex, and risky with no guarantee of success. Also, the improvements in techniques applied in genomics, proteomics, computational biology, and clinical trials significantly increase the data complexity and volume, which imposes higher requirements on the drug development pipeline. In recent years, machine learning (ML) methods were employed to support drug development in various aspects …

Clustering And Analysis Of G Quadruplex Sequences., Aryan Neupane

Electronic Theses and Dissertations

G quadruplex structures are secondary structures located throughout the genome of various organisms with involvement in regulatory functions in different transcription, translation, genome stability, epigenetic regulation as well as cell division. Even with the diverse acknowledgement of G4 structure in vivo, there are no current search tools for G quadruplexes based on already identified G quadruplexes and identified families across different genomes based on sequence diversity. Construction of families of G4 sequences and identifying their polymorphisms within disease and disorders will lead to a better understanding of their functional roles and will further research into the biophysical modeling of interactions …

Integrating Omim And Intact Data For The Analysis Of Gene-Phenotype Interactions In Complex Diseases: A Linux-Based Computational Tool For Network Analysis, Devin Keane

All Theses

The field of genetics is constantly evolving. New advances in bioinformatics and computational approaches are leading to exciting new developments in our ability to treat and prevent diseases. Computational genetics provides valuable insights into the complex mechanisms and layers of biological communication that shape an organism's phenotype. Understanding these mechanisms is critical to advancing human health.

The study of diseases in genetics requires a comprehensive understanding of the interactions between various biological processes, including gene expression, protein synthesis, RNA, metabolism, and cell-cell communication. To effectively address the root causes of such diseases, multi-disciplinary approaches that integrate information from different levels …

Reconstructing Mutational Lineages In Breast Cancer By Multi-Patient-Targeted Single Cell Dna Sequencing, Jake Leighton

Dissertations and Theses (Open Access)

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high rates of metastasis and recurrence, where TNBC patients have a poor 5-year survival and ~50% are non-responsive to chemotherapy. Aneuploidy is a cancer hallmark that is pervasive in over 90% of breast cancer patients and is indicative of complex genomic rearrangements that are acquired during tumor initiation. Although copy number aberrations have been extensively studied in relation to aneuploidy and TNBC initiation, little is currently known regarding the timing and impact of single nucleotide variants (SNVs) contributing to these early transformative genomic events. Paramount to novel …

Effects Of Cyanobacteria Harmful Algal Blooms On The Microbial Community Within Lake Okeechobee, Fl, Usa, Paisley S. Samuel

All HCAS Student Capstones, Theses, and Dissertations

The Lake Okeechobee (Lake O) watershed is a Floridian freshwater ecosystem that has been affected by the increased frequency and intensity of harmful cyanobacterial bloom (cyanoHAB) events occurring over recent decades. Lake O has several ecological and economic purposes such as providing habitats for various organisms and providing drinking water to urban communities surrounding the lake. Toxic cyanoHAB events are posing a threat to the ecosystem and economy of the lake due to the degradation of water quality. This study investigates how the microbial community structure within Lake O is affected by annual cyanobacterial harmful algal blooms over several years …

Soil Microbial Community Composition Of White Oak Mountain, Tennessee, Matthew Gano, Timothy D. Trott

Research in Biology

Abstract - Soil microbial communities are responsible for nutrient cycling in terrestrial ecosystems and have symbiotic and parasitic relationships with the plant community. However, little is known about the factors that determine the soil microbial community composition. In this study we examined how spring wildflower diversity and geographical factors influence the soil microbial community composition of the second growth oak hickory forests of White Oak Mountain in Southeast Tennessee. The characterization of the soil microbial community was completed with 16S/18S/ITS rDNA amplicon sequencing of total DNA extracted from soil samples that were normalized for each sample plot. Here we characterize …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Identifying Non-Traditional Slippery Sequences Associated With Translational Frameshifts, Aaron J. Gin, Kari Lynn Clase

Graduate Industrial Research Symposium

Genetic frameshifts are a mutation in which
a nucleotide skip leads to a shift in the
reading frame. In viruses, these frameshifts
can be programmed using a slippery
sequence to bypass the stop codon
associated with the initial protein. This
allows for variable control of protein
expression. In bacteriophages, translational
frameshifts have been identified but only a
few have been proven experimentally. Using
experimental data and comparative
genomics, non-traditional slippery
sequences can be identified as assisting in
controlling the protein coding throughout
viruses. Novel slippery sequences can aid in
the understanding of protein expression in
biological environments and further the …

Characterization Of Cell Type-Specific Molecular Heterogeneity In Cancer Using Multi-Omic Approaches, Min Kyung Lee

Dartmouth College Ph.D Dissertations

Tumors are composed of heterogeneous cell types each with its own unique molecular profiles. Recent advances in single cell genomics technologies have begun to increase our understanding of the molecular heterogeneity that exists in tumors with particular focus on gene expression and chromatin accessibility profiles. However, due to limitations in methods for certain sample types and high cost for single cell genomics, bulk tumor molecular profiling has been and remains widely used. In addition, other facets of single cell epigenomic profiling, particularly methylation and hydroxymethylation, remains underexplored. Thus, investigations to understand the cell type specific epigenetic heterogeneity and the cooperation …

Intergenic Transcription In In Vivo Developed Bovine Oocytes And Pre-Implantation Embryos, Saurav Ranjitkar, Mohammad Shiri, Jiangwen Sun, Xiuchun Tian

Computer Science Faculty Publications

Background

Intergenic transcription, either failure to terminate at the transcription end site (TES), or transcription initiation at other intergenic regions, is present in cultured cells and enhanced in the presence of stressors such as viral infection. Transcription termination failure has not been characterized in natural biological samples such as pre-implantation embryos which express more than 10,000 genes and undergo drastic changes in DNA methylation.

Results

Using Automatic Readthrough Transcription Detection (ARTDeco) and data of in vivo developed bovine oocytes and embryos, we found abundant intergenic transcripts that we termed as read-outs (transcribed from 5 to 15 kb after TES) and …

Adjusting For Gene-Specific Covariates To Improve Rna-Seq Analysis, Hyeongseon Jeon, Kyu-Sang Lim, Yet Nguyen, Dan Nettleton

Mathematics & Statistics Faculty Publications

Summary

This paper suggests a novel positive false discovery rate (pFDR) controlling method for testing gene-specific hypotheses using a gene-specific covariate variable, such as gene length. We suppose the null probability depends on the covariate variable. In this context, we propose a rejection rule that accounts for heterogeneity among tests by employing two distinct types of null probabilities. We establish a pFDR estimator for a given rejection rule by following Storey's q-value framework. A condition on a type 1 error posterior probability is provided that equivalently characterizes our rejection rule. We also present a suitable procedure for selecting a tuning …