Digital Commons Network^™

Evolution Of Overlapping Reading Frames In Virus Genomes, Laura Muñoz Baena

Electronic Thesis and Dissertation Repository

Viruses are formidable pathogens that represent the majority of biological entities in our planet, and their genomes are a source of interesting enigmas. One feature in which virus genomes are usually rich, is the presence of overlapping reading frames (OvRFs) — portions of the genome where the same nucleotide sequence encodes more than one protein. OvRFs are hypothesized to be used by viruses to encode proteins more compactly and to regulate transcription. In addition, OvRFs might be a source of gene novelty, facilitating the creation of new open reading frames (ORF) within the transcriptional context of existing ones.

To characterize …

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 …

Gene Regulatory Context Of Honey Bee Worker Sterility, Rahul Choorakkat Unnikrishnan

Electronic Thesis and Dissertation Repository

Honey bee workers deactivate their ovaries and are functionally sterile when a queen is present in the colony. I adopt a bioinformatics approach to up-date a model transcriptional regulatory network (TRN) to study gene-regulatory processes that regulate fecundity in workers. On splitting the network, I obtained nine clusters and each cluster conformed to properties associated with real-world networks. Two of the nine clusters are enriched for 'sterility genes' and contained single well-connected hub genes (GB44769, ftz-f1). The genes in the two clusters were functionally enriched for nucleic acid binding (GO:0003676) and nucleotide binding (GO:0000166). I identified homologous genes for …

Towards More Complete Metagenomic Analyses Through Circularized Genomes And Conjugative Elements, Benjamin R. Joris

Electronic Thesis and Dissertation Repository

Advancements in sequencing technologies have revolutionized biological sciences and led to the emergence of a number of fields of research. One such field of research is metagenomics, which is the study of the genomic content of complex communities of bacteria. The goal of this thesis was to contribute computational methodology that can maximize the data generated in these studies and to apply these protocols human and environmental metagenomic samples.

Standard metagenomic analyses include a step for binning of assembled contigs, which has previously been shown to exclude mobile genetic elements, and I demonstrated that this phenomenon extends to all conjugative …

Response Of The Soil Bacterial Community, Resistome, And Mobilome To A Decade Of Macrolide Antibiotic Contamination, Liam Paul Brown

Electronic Thesis and Dissertation Repository

Biosolids (treated sewage sludge) are used as agricultural fertilizer but are frequently contaminated with macrolide antibiotics, to which resistance is rising among historically susceptible bacteria. To determine if the land-application of macrolides carried in biosolids could promote antibiotic resistance in soil bacteria, soil plots were exposed annually to environmentally realistic or high doses of macrolides for ten years. I sequenced the bacterial 16S ribosomal DNA, metagenomic DNA, and integron gene cassettes within the treated and antibiotic-free soil to compare the compositions and diversities of the bacterial communities, antibiotic resistance genes, and mobile genetic elements. I determined that the high dose …

Visualization And Interpretation Of Protein Interactions, Dipanjan Chatterjee

Electronic Thesis and Dissertation Repository

Visualization and interpretation of deep learning models' prediction is a very important area of research in machine learning nowadays. Researchers are not only focused on generating a model with good performance, but also they want to trust the model. Our aim in this thesis is to adapt existing interpretation methods to a protein-protein binding site prediction problem to visualize and understand the model's prediction and learning pattern.

We present three deep learning-based interpretation methods: sensitivity analysis, saliency map and integrated gradients to analyze the amino acid residues which create positive and negative relevance to the deep learning models' prediction. As …

Deciphering The Ck2-Dependent Phosphoproteome And Its Integration With Regulatory Ptm Networks, Teresa Nunez De Villavicencio Diaz

Electronic Thesis and Dissertation Repository

Protein functions are regulated by the post-translational addition of covalent modifications on certain amino acids. Depending on their distance within the 3-dimensional structure, addition/removal of individual post translational modifications (PTMs) can be impacted by others. This PTM interplay constitutes an essential regulatory mechanism that interconnects the molecular networks in the cell. Protein CK2, a clinically relevant acidophilic Ser/Thr kinase, may be responsible for 10-20% of the human phosphoproteome. Such estimates agree with the number of known substrates, which continues to expand. Furthermore, the demonstration that CK2 participates in hierarchical phosphorylation and has similar sequence determinants to caspases suggest extensive PTM …

Hpv Mediated Antagonism Of The Il-18 Proinflammatory Pathway In Head And Neck Cancer, Wyatt W. Anderson

Electronic Thesis and Dissertation Repository

In this thesis, I examined the effect of human papillomavirus (HPV) on the proinflammatory IL-18 cytokine pathway in head and neck cancers. I investigated the expression and methylation of genes associated with this pathway using The Cancer Genome Atlas (TCGA) data. In HPV+ cancers, IL18, CASP1, and AIM2 were downregulated, while IL18BP was upregulated compared to HPV- cancers and adjacent non-cancerous tissues, and IL18’s promoter was significantly more methylated. I compared HPV+ and HPV- head and neck cancer cell lines for expression of RNA and protein levels of IL-18 and IL-18BP by qPCR, western blot, and ELISA. IL-18 …

Mathematical Modelling Of Prophage Dynamics, Tyler Pattenden

Electronic Thesis and Dissertation Repository

We use mathematical models to study prophages, viral genetic sequences carried by bacterial genomes. In this work, we first examine the role that plasmid prophage play in the survival of de novo beneficial mutations for the associated temperate bacteriophage. Through the use of a life-history model, we determine that mutations first occurring in a plasmid prophage are far more likely to survive drift than those first occurring in a free phage. We then analyse the equilibria and stability of a system of ordinary differential equations that describe temperate phage-host dynamics. We elucidate conditions on dimensionless parameters to determine a parameter …

Machine Learning With Digital Signal Processing For Rapid And Accurate Alignment-Free Genome Analysis: From Methodological Design To A Covid-19 Case Study, Gurjit Singh Randhawa

Electronic Thesis and Dissertation Repository

In the field of bioinformatics, taxonomic classification is the scientific practice of identifying, naming, and grouping of organisms based on their similarities and differences. The problem of taxonomic classification is of immense importance considering that nearly 86% of existing species on Earth and 91% of marine species remain unclassified. Due to the magnitude of the datasets, the need exists for an approach and software tool that is scalable enough to handle large datasets and can be used for rapid sequence comparison and analysis. We propose ML-DSP, a stand-alone alignment-free software tool that uses Machine Learning and Digital Signal Processing to …

Mhcherrypan, A Novel Model To Predict The Binding Affinity Of Pan-Specific Class I Hla-Peptide, Xuezhi Xie

Electronic Thesis and Dissertation Repository

The human leukocyte antigen (HLA) system or complex plays an essential role in regulating the immune system in humans. Accurate prediction of peptide binding with HLA can efficiently help to identify those neoantigens, which potentially make a big difference in immune drug development. HLA is one of the most polymorphic genetic systems in humans, and thousands of HLA allelic versions exist. Due to the high polymorphism of HLA complex, it is still pretty difficult to accurately predict the binding affinity. In this thesis, we presented a new algorithm to combine convolutional neural network and long short-term memory to solve this …

Efficient Alignment Algorithms For Dna Sequencing Data, Nilesh Vinod Khiste

Electronic Thesis and Dissertation Repository

The DNA Next Generation Sequencing (NGS) technologies produce data at a low cost, enabling their application to many ambitious fields such as cancer research, disease control, personalized medicine etc. However, even after a decade of research, the modern aligners and assemblers are far from providing efficient and error free genome alignments and assemblies respectively. This is due to the inherent nature of the genome alignment and assembly problem, which involves many complexities. Many algorithms to address this problem have been proposed over the years, but there still is a huge scope for improvement in this research space.

Many new genome …

Error Correction And De Novo Genome Assembly Of Dna Sequencing Data, Michael Z. Molnar

Electronic Thesis and Dissertation Repository

The ability to obtain the genetic code of any species has caused a revolution in biological sciences. Current technologies are capable of sequencing short pieces of DNA with very high quality. These short pieces of DNA determint the sequence of bases in the genome of any species. This information is key in understanding many of the aspects of how life functions.

The accuracy of sequencing is extremely important since the differences between individuals of the same species are caused by very few changes. All sequencing technologies make errors, and before the data can be used for downstream applications it is …

Bioinformatics And Next Generation Sequencing: Applications Of Arthropod Genomes, Zaichao Zhang

Electronic Thesis and Dissertation Repository

Over the past decade, the Next Generation Sequencing (NGS) technology has been broadly applied in many areas such as genomics, medical diagnosis, biotechnology, virology, biological systematics, forensic biology, and anthropology. Taken together, it has offered us brilliant insights into life sciences. Most of the work presented in this thesis describes NGS applications on genome assembly, genome annotation, and comparative genomics, using arthropods as case studies: (1) by sequencing and analyzing the genomes of three Tetranychus spider mites with three completely different feeding behaviors, we uncovered genomic signature variations and indicative of pest adaptations; (2) we sequenced, assembled and annotated five …

Measuring The Human Gut Microbiome: New Tools And Non Alcoholic Fatty Liver Disease, Ruth G. Wong

Electronic Thesis and Dissertation Repository

With the advent of next generation DNA and RNA sequencing, scientists can obtain a more comprehensive snapshot of the bacterial communities on the human body (known as the `human microbiome'), leading to information about the bacterial composition, what genes are present, and what proteins are produced. The scientific community is in a phase of developing the experiments and accompanying statistical techniques to investigate the mechanisms by which the human microbiome affects health and disease. In this thesis, I explore alternatives to the standard weighted and unweighted UniFrac distance metric that measure the difference between microbiome samples. These alternative weightings allow …

Error Correction In Next Generation Dna Sequencing Data, Michael Z. Molnar

Electronic Thesis and Dissertation Repository

Motivation: High throughput Next Generation Sequencing (NGS) technologies can sequence the genome of a species quickly and cheaply. Errors that are introduced by NGS technologies limit the full potential of the applications that rely on their data. Current techniques used to correct these errors are not sufficient, and a more efficient and accurate program is needed to correct errors.

Results: We have designed and implemented RACER (Rapid Accurate Correction of Errors in Reads), an error correction program that targets the Illumina genome sequencer, which is currently the dominant NGS technology. RACER combines advanced data structures with an intricate analysis of …