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Full-Text Articles in Life Sciences
Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra
Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra
Dissertations & Theses (Open Access)
Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …
A Mechanistic And Genomic Analysis Of Molluscum Contagiosum Virus Immune Evasion, Ian Benjamin Harvey
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 …
Sequence Analysis Methods For The Design Of Cancer Vaccines That Target Tumor-Specific Mutant Antigens (Neoantigens), Jasreet Hundal
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 …
A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey
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 …
Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar
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 …
Whole Genome Sequencing As A Tool For Identifying Phenotypic Properties And Underlying Genetic Mechanisms In Staphylococcus Pseudintermedius, Matthew C. Riley
Whole Genome Sequencing As A Tool For Identifying Phenotypic Properties And Underlying Genetic Mechanisms In Staphylococcus Pseudintermedius, Matthew C. Riley
Doctoral Dissertations
Staphylococcus pseudintermedius is a Gram-positive bacterial opportunistic pathogen commonly associated with dermal infections in canines, but capable of causing serious disease in other species. Reports of human infections caused by S. pseudintermedius along with an increase in resistance to multiple antibiotics highlights the importance of this organism. Whole genome sequencing can allow large scale investigation of genetic mechanisms underlying phenotypic properties that contribute to the expansion of successful S. pseudintermedius clonal lineages.
The increase in multidrug and methicillin-resistant S. pseudintermedius (MRSP) may result from horizontal transfer of genetic material between bacterial isolates, yet is thought to be rare in Staphylococci …