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Articles 1 - 10 of 10
Full-Text Articles in Computational Biology
Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy
Dissertations and Theses (Open Access)
Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …
Epigenetic Modification As A Therapeutic Target In Brafv600e-Mutated Metastatic Colorectal Cancer, Hey Min Lee
Epigenetic Modification As A Therapeutic Target In Brafv600e-Mutated Metastatic Colorectal Cancer, Hey Min Lee
Dissertations and Theses (Open Access)
Patients with BRAFV600E-mutated metastatic colorectal cancer (mCRC) experience a worse prognosis and demonstrate only a 5% response rate to BRAF inhibitor treatment. In this study, adaptive resistance, and a potential combination of standard therapies in BRAFV600E CRC were unveiled. Intriguingly, a robust association of BRAFV600E mutation and DNA hypermethylation suggests this is a unique subgroup harboring aberrant epigenetic phenotype. Firstly, DNA methyltransferase (DNMT) inhibitor treatment induced profound DNA hypomethylation in vivo, but minimal change in gene expression due to adaptive elevation of the repressive histone methylation, H3K27me3, leading to compensatory suppression of key tumor suppressor genes, …
Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang
Dartmouth College Ph.D Dissertations
DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …
Methylation Patterns Across Tissue Type And Time In Peromyscus Leucopus: A Targeted Museum Study, Loryn Smith
Methylation Patterns Across Tissue Type And Time In Peromyscus Leucopus: A Targeted Museum Study, Loryn Smith
Master's Theses or Doctor of Nursing Practice
Museum specimens are a vital data source for many types of studies. One relatively new use includes studying methylation patterns. Methylation patterns are a form of epigenetics or how gene expression changes without alteration of the genetic code. These patterns have been examined in many mammals. However, the focus has previously been on overall epigenetic patterns. Few studies have investigated whether methylation patterns differ across tissue types, time, or preservation method. In this study, I compared methylation patterns in muscle, liver, toe pads, and nasal bones from Peromyscus leucopus (white-footed mouse) museum specimens collected in 2022, 2018, 2014, and 2008 …
An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan
An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan
Dissertations and Theses (Open Access)
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …
Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula
Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula
Dissertations and 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 …
Molecular Consequences Of High Taz Expression In Gliomas, Visweswaran Ravikumar
Molecular Consequences Of High Taz Expression In Gliomas, Visweswaran Ravikumar
Dissertations and Theses (Open Access)
Diffuse high grade gliomas are complex and lethal neoplasms of the adult central nervous system that are driven by a range of genetic and epigenetic alterations. Molecular classification of these tumors has identified different transcriptional subtypes, the most notable being Proneural (PN) and Mesenchymal (MES) classes. The most aggressive forms of the disease have a Mesenchymal expression signature, with reported PN-to-MES transition occurring with tumor progression. Master regulatory analysis has identified the transcriptional co-activator TAZ (WWTR1) as a major driver of the MES transition. Overexpression of this single protein in glioma stem cells has been shown to drive a transition …
Characterizing Epigenetic Regulation In The Developing Chicken Retina, Bejan Abbas Rasoul
Characterizing Epigenetic Regulation In The Developing Chicken Retina, Bejan Abbas Rasoul
Masters Theses, 2010-2019
The retina, the sensory neuronal tissue within the eye, is composed of three layers of neuronal cells connected by two synaptic layers lining the inside of the anterior portion of the eye. Multipotent retinal precursor cells are genetically homogeneous and differentiate into mature retinal neurons due to differential gene expression. Differences in gene expression have been correlated with epigenetic modifications such as DNA methylation. DNA methylation of upstream regulatory elements is associated with transcriptional silencing of gene expression. Years of research in retinal development has identified the numerous genes expressed during the main steps of retinal development, however, it is …
Meta-Analysis Of Dna Methylation And Expression In Liver Cancer Patients, Daniele Todorov, Barbara Stefanska, Katarzyna Lubecka-Pietruszewska
Meta-Analysis Of Dna Methylation And Expression In Liver Cancer Patients, Daniele Todorov, Barbara Stefanska, Katarzyna Lubecka-Pietruszewska
The Summer Undergraduate Research Fellowship (SURF) Symposium
Hepatocellular carcinoma (HCC), the most common liver cancer, is the second leading cause of cancer-related death worldwide. HCC is often diagnosed at late stages, for which there are no effective chemotherapies. Biomarkers unique to HCC patients could be used to detect HCC early and improve treatment. In the present project, we have performed a meta-analysis to compare the gene-specific DNA methylation and gene expression patterns of HCC patients as reported by four independent studies. Our goal was to discover the strongest changes that distinguish HCC from normal tissue. The relationship between methylation and expression in HCC was examined and genes …
On The Origin Of Phenotypic Variation: Novel Technologies To Dissect Molecular Determinants Of Phenotype, Francesco Vallania
On The Origin Of Phenotypic Variation: Novel Technologies To Dissect Molecular Determinants Of Phenotype, Francesco Vallania
All Theses and Dissertations (ETDs)
This thesis describes the conception, design, and development of novel computational tools, theoretical models, and experimental techniques applied to the dissection of molecular factors underlying phenotypic variation. The first part of my work is focused on finding rare genetic variants in pooled DNA samples, leading to the development of a novel set of algorithms, SNPseeker and SPLINTER, applied to next-generation sequencing data. The second part of my work describes the creation of a reporter system for DNA methylation for the purpose of dissecting the genetic contribution of tissue-specific patterns of DNA methylation across the genome. Finally the last part of …