Computational Biology Commons^™

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 …

Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula

Dissertations & Theses (Open Access)

G-quadruplexes are non-B DNA structures formed by four or more runs of repeated guanines that confer unique features to living organism’s genomes. These sequences are enriched in regulatory regions, such as promoters and 5’ UTRs, and have distinct regulatory roles in both health and disease states. Even though previous studies showed the impact of G4 in gene expression, none of them summarized the location-specific effect of G4. Also, there is no broad understanding about the most common G4 repeat in the human genome, named here as G4-22, and how it links to the evolution of mammals and their biology. In …

Comparative Genomics Methods And Applications, Emily N. Alden

Biomedical Sciences ETDs

Virtually all fields of biology have benefited from the advancements in comparative genomics technologies, specifically in the study of evolution. In this dissertation I develop and use comparative genomic technologies to investigate the novel SARS-CoV-2 virus, assembly the first genome of the black lace domestic angelfish and identify germline genetic variants associated with altered breast cancer-specific survival. Our genome tiling array for the novel coronavirus presents a rapid and cost-effective method to sequence the entire viral genome and can be used to track the rapid evolution of viral variants in the population. The domestic angelfish is a member of the …

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv

Dissertations & Theses (Open Access)

Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …

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 …

Computational Genomic Models For Spatio-Temporal Investigation Of Early Lung Cancer Pathology, Smruthy Sivakumar

Dissertations & Theses (Open Access)

Lung cancer, of which non-small cell lung cancer (NSCLC) is the most common form, is the second most prevalent cancer and the leading cause of cancer-related deaths. NSCLCs primarily comprise adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). Advances in early detection and prevention have been limited by the lack of early-stage biomarkers and targets. A comprehensive molecular characterization of premalignant lesions and tumor-adjacent normal tissue can aid in better understanding NSCLC pathogenesis. However, these investigations are further challenged by limited tissue availability and low cellular fractions of detectable somatic mutations.

Therefore, there is a dearth of knowledge about the pathogenesis …

Development Of An In Silico Kir Genotyping Algorithm And Its Application To Population And Cancer Immunogenetic Analyses, Howard Rosoff

Dissertations & Theses (Open Access)

Gene content determination and variant calling in the complex KIR genomic region are useful for immune system function analysis, pathogenesis and disease risk factor elucidation, immunotherapy development, evolutionary investigations, and human migration modeling. Sequence-specific oligonucleotide and sequence-specific primer PCR methods are the de facto standards for KIR presence/absence identification, but the current platforms are unsuitable for SNP calling, impractical for KIR typing large cohorts of DNA samples, and inapplicable for typing repositories in which sequence data, but not cells or cell analytes, are available. Alternative typing methods, such as in silico sequence-based typing, can address the problems associated with amplicon-based …

Hpcnmf: A High-Performance Toolbox For Non-Negative Matrix Factorization, Karthik Devarajan, Guoli Wang

COBRA Preprint Series

Non-negative matrix factorization (NMF) is a widely used machine learning algorithm for dimension reduction of large-scale data. It has found successful applications in a variety of fields such as computational biology, neuroscience, natural language processing, information retrieval, image processing and speech recognition. In bioinformatics, for example, it has been used to extract patterns and profiles from genomic and text-mining data as well as in protein sequence and structure analysis. While the scientific performance of NMF is very promising in dealing with high dimensional data sets and complex data structures, its computational cost is high and sometimes could be critical for …

Introduction To Gene Enrichment Analysis Tools, Rolando Garcia-Milian

Rolando Garcia-Milian

Bioinformatics enrichment tools play an important role in identifying, annotating, and functionally analyzing large list of genes generated by high-throughput technologies (e.g. microarrary, RNA-seq, ChIP-chip). This workshop will provide an overview of the principle, type of enrichments, and the infrastructure of enrichment tools. By using concrete examples, it will also introduce some of the most popular tools for gene enrichment analysis such as DAVID, GSEA, and WebGestalt.

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 …

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 …

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 …