Life Sciences Commons^™

A Mechanistic And Genomic Analysis Of Molluscum Contagiosum Virus Immune Evasion, Ian Benjamin Harvey

Arts & Sciences Electronic Theses and Dissertations

Molluscum contagiosum virus (MCV) is a common human-specific poxvirus with a proclivity for

infecting children and the immune-compromised. A characteristic MCV infection is restricted to

the epidermal layers of the skin and can persist for weeks to years in an otherwise healthy

individual. The high clinical burden of MCV is at odds with our limited knowledge regarding how

it successfully evades the human immune response, which is in part due to the lack of an animal

model or cell line to propagate the virus. Through this dissertation, we have uncovered and

characterized a novel mechanism by which MC80, a protein …

A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey

Arts & Sciences Electronic Theses and Dissertations

The implementation of next-generation genomic sequencing has exploded over the past dozen years. Large consortia, such as The Cancer Genome Atlas (TCGA); the International Cancer Genetics Consortium (ICGC); and the Pediatric Cancer Genome Projects (PCGP), made great strides in democratizing big data for the scientific community. These data sets provide a rich resource to build tools for somatic variant discovery and exploratory analysis. Public repositories hold the answer to many novel biological and clinical revelations i.e., the discovery of complex indels, splice creating mutations, alternative super enhancer binding sites, machine learning models to predict mutation impact, and cancer subtype classification …

Sequence Analysis Methods For The Design Of Cancer Vaccines That Target Tumor-Specific Mutant Antigens (Neoantigens), Jasreet Hundal

Arts & Sciences Electronic Theses and Dissertations

The human adaptive immune system is programmed to distinguish between self and non-self proteins and if trained to recognize markers unique to a cancer, it may be possible to stimulate the selective destruction of cancer cells. Therapeutic cancer vaccines aim to boost the immune system by selectively increasing the population of T cells specifically targeted to the tumor-unique antigens, thereby initiating cancer cell death.. In the past, this approach has primarily focused on targeted selection of ‘shared’ tumor antigens, found across many patients. The advent of massively parallel sequencing and specialized analytical approaches has enabled more efficient characterization of tumor-specific …

Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar

Arts & Sciences Electronic Theses and Dissertations

Paired tumor-normal sequencing of thousands of patient’s exomes has revealed millions of somatic mutations, but functional characterization and clinical decision making are stymied because biologically neutral ‘passenger’ mutations greatly outnumber pathogenic ‘driver’ mutations. Since most mutations will return negative results if tested, conventional resource-intensive experiments are reserved for mutations which are observed in multiple patients or rarer mutations found in well-established cancer genes. Most mutations are therefore never tested, diminishing the potential to discover new mechanisms of cancer development and treatment opportunities. Computational methods that reliably prioritize mutations for testing would greatly increase the translation of sequencing results to clinical …