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Full-Text Articles in Bioinformatics

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv Dec 2020

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, …


Integrated Multiparametric Radiomics And Informatics System For Characterizing Breast Tumor Characteristics With The Oncotypedx Gene Assay, Michael A. Jacobs, Christopher B. Umbricht, Vishwa S. Parekh, Riham H. El Khouli, Leslie Cope, Katarzyna J. Macura, Susan Harvey, Antonio C. Wolff Sep 2020

Integrated Multiparametric Radiomics And Informatics System For Characterizing Breast Tumor Characteristics With The Oncotypedx Gene Assay, Michael A. Jacobs, Christopher B. Umbricht, Vishwa S. Parekh, Riham H. El Khouli, Leslie Cope, Katarzyna J. Macura, Susan Harvey, Antonio C. Wolff

Radiology Faculty Publications

Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained …


Genomic And Transcriptomic Alterations In Metabolic Regulators And Implications For Anti-Tumoral Immune Response, Ryan J. King Aug 2020

Genomic And Transcriptomic Alterations In Metabolic Regulators And Implications For Anti-Tumoral Immune Response, Ryan J. King

Theses & Dissertations

Metabolic and immune alterations are ubiquitous hallmarks of cancer that are established during the foundational mutations and are further selected upon to generate highly aggressive tumors. Recent evidence suggests that cancer cells employ an altered metabolism to induce immune evasion. To further discover the relationship between metabolism and immunity in cancer, this thesis aimed to discover potential candidates of interest by first examining the mucin family for differences, as they exert a wide range of activities in cancer, including altered metabolism and immune alterations. Unique differences lead to further profiling in pancreatic and esophageal cancer. In pancreatic cancer, CD73 was …


Survival-Related Clustering Of Cancer Patients By Integrating Clinical And Biological Datasets, Xinming Wei Jul 2020

Survival-Related Clustering Of Cancer Patients By Integrating Clinical And Biological Datasets, Xinming Wei

Master's Theses (2009 -)

Subtype-based treatments and drug therapies are essential aspects to be considered in cancer patients' clinical trials to provide appropriate personalized therapies. With the advancement of the next-generation sequencing technology, several computational models, integrating genomic and transcriptomic datasets (i.e., multi-omics) in the prediction of subtype-based classification in cancer patients, were emerged. However, integration of the prognostic features from the clinical data, related to survival risks with the multi-omics datasets in the prediction of different subtypes, is limited and an important research area to be explored. In this study, we proposed a data integration pipeline with the prognostic features from the clinical …


B Cell Acute Lymphoblastic Leukemia Is Driven By Activating Janus Kinase Mutations Cooperating With Spi1 And Spib Deletions In A Murine Model, Michelle Lim Jun 2020

B Cell Acute Lymphoblastic Leukemia Is Driven By Activating Janus Kinase Mutations Cooperating With Spi1 And Spib Deletions In A Murine Model, Michelle Lim

Electronic Thesis and Dissertation Repository

B cell acute lymphoblastic leukemia (B-ALL) is caused by genetic lesions in developing B cells that function as drivers for accumulation of additional mutations in an evolutionary selection process. We investigated secondary drivers of leukemogenesis and their mechanism(s) of arising in a mouse model of B-ALL driven by PU.1/Spi-B deletion (Mb1-CreDPB). Whole exome sequencing revealed recurrent mutations in Jak3 (encoding Janus Kinase 3) and Jak1. Mutations with high variant allele frequency (VAF) were dominated by C->T transition mutations that were compatible with AID, whereas the majority of mutations, with low VAF, were dominated by C->A transversions associated with …


Multi-Omics Integration For Gene Fusion Discovery And Somatic Mutation Haplotyping In Cancer, Steven Mason Foltz May 2020

Multi-Omics Integration For Gene Fusion Discovery And Somatic Mutation Haplotyping In Cancer, Steven Mason Foltz

Arts & Sciences Electronic Theses and Dissertations

Cancer is a disease caused by changes to the genome and dysregulation of gene expression. Among many types of mutations, including point mutations, small insertions and deletions, large scale structural variants, and copy number changes, gene fusions are another category of genomic and transcriptomic alteration that can lead to cancer and which can serve as therapeutic targets. We studied gene fusion events using data from The Cancer Genome Atlas, including over 9,000 patients from 33 cancer types, finding patterns of gene fusion events and dysregulation of gene expression within and across cancer types. With data from the CoMMpass study (Multiple …


The Role Of The Cxcr3 Signaling Axes In Pancreatic Ductal Adenocarcinoma, Andrew C. Cannon May 2020

The Role Of The Cxcr3 Signaling Axes In Pancreatic Ductal Adenocarcinoma, Andrew C. Cannon

Theses & Dissertations

Numerous cytokines promote pancreatic ductal adenocarcinoma (PDAC) progression and suppress anti-tumor immune response leading to poor prognosis in PDAC patients. Despite this, many cytokines, have not been investigated in PDAC. Bioinformatic analyses of PDAC microarray and RNA-Seq datasets were used to identify cytokines overexpressed in PDAC, confirm the expression of cognate receptors, determine the association of cytokines with patient survival and define key underlying molecular associations. Bioinformatic findings were validated using immunohistochemical (IHC) staining, comparative cytokine qPCR-array in KrasLSL-G12D:TP53LSL-R172H:Pdx1-Cre (KPC) and KrasLSL-G12D:Pdx1-Cre (KC) PDAC models and multicolor immunofluorescence staining. Tail-vein injections of PDAC cells …