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Full-Text Articles in Bioinformatics
The Splice Is Not Right: Splice-Site-Creating Mutations In Cancer Genomes, Reyka Glencora Jayasinghe
The Splice Is Not Right: Splice-Site-Creating Mutations In Cancer Genomes, Reyka Glencora Jayasinghe
Arts & Sciences Electronic Theses and Dissertations
Accurate interpretation of cancer mutations in individual tumors is a prerequisite for precision medicine. Large-scale sequencing studies, such as The Cancer Genome Atlas (TCGA) project, have worked to address the functional consequences of genomic mutations, with the larger goal of determining the underlying mechanisms of cancer initiation and progression. Many studies have focused on characterizing non-synonymous somatic mutations that alter amino acid sequence, as well as splice disrupting mutations at splice donors and acceptors. Current annotation methods typically classify mutations as disruptors of splicing if they fall on the consensus intronic dinucleotide splice donor, GT, the splice acceptor, AG. Splice …
Multi-Omics Portraits Of Cancer, Kuan-Lin Huang
Multi-Omics Portraits Of Cancer, Kuan-Lin Huang
Arts & Sciences Electronic Theses and Dissertations
Precision oncology demands accurate portrayal of a disease at all molecular levels. However, current large-scale studies of omics are often isolated by data types. I have been developing computational tools to conduct integrative analyses of omics data, identifying unique molecular etiology in each tumor. Particularly, this dissertation presents the following contributions to the computational omics of cancer: (1) uncovering the predisposition landscape in 33 cancers and how germline genome collaborates with somatic alterations in oncogenesis; (2) pioneering methods to combine genomic and proteomic data to identify treatment opportunities; and (3) revealing selective phosphorylation of kinase-substrate pairs. These findings advance our …
Computational Insights Into The Generation Of Chromosomal Copy Number Changes, Yihua Liu
Computational Insights Into The Generation Of Chromosomal Copy Number Changes, Yihua Liu
Dissertations & Theses (Open Access)
Deviations from a diploid configuration of the human genome, spanning single genes or entire chromosomes, can have wide-ranging impacts on the variation of human phenotypes, including Mendelian and complex forms of diseases. These chromosomal alterations — such as duplications, deletions or copy-neutral loss-of-heterozygosity — are thus important forms of genetic variation for phenotyping populations of individuals as well as populations of cells. Indeed, copy number variants (CNVs) serve as hallmarks of critical changes in the development of particular diseases such as cancer and thus may be used as biomarkers. These CNVs may be either inherited (transmitted by germ cells, originating …
The Role Of Thymine-Dna Glycosylase In Transcriptional Regulation, Bart Kolendowski
The Role Of Thymine-Dna Glycosylase In Transcriptional Regulation, Bart Kolendowski
Electronic Thesis and Dissertation Repository
Precise control over transcriptional regulation is required for normal cell function. Errors in transcriptional regulation underpin many diseases including cancer. Thymine DNA Glycosylase (TDG) is a base excision repair protein and a coregulator that has been implicated in a diverse set of fundamental biological processes including embryonic development, nuclear receptor signaling and Wnt signaling. Importantly, TDG has been shown to play an important role in transcriptional regulation in a wide variety of systems. Details surrounding the mechanism through which TDG acts remain unclear. In this thesis we explore the role of TDG in Estrogen Receptor (ER)-dependent signaling and in cellular …
Missing Heritability And Novel Germline Risk Loci In Hereditary Ovarian Cancer: Insights From Whole Exome Sequencing And Functional Analyses, Jaime Lyn Stafford
Missing Heritability And Novel Germline Risk Loci In Hereditary Ovarian Cancer: Insights From Whole Exome Sequencing And Functional Analyses, Jaime Lyn Stafford
Wayne State University Dissertations
While 25% of ovarian cancer (OVCA) cases are due to inherited factors, most of the genetic risk remains unexplained. This study addressed this gap by identifying previously undescribed OVCA risk loci through the whole exome sequencing (WES) of 48 BRCA1/BRCA2 wild type women diagnosed with OVCA, selected for high risk of genetic inheritance. Five clearly pathogenic variants were identified in this sample, four of which are in two genes featured on current multi-gene panels; (RAD51D, ATM). In addition, a high impact variant in FANCM (R1931*) was identified. FANCM has been recently implicated in familial breast cancer risk but is not …