Open Access Theses and Dissertations

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You searched for subject:(tumor somatic mutations). Showing records 1 – 2 of 2 total matches.

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Vanderbilt University

1. Song, Zhuo. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.

Degree: PhD, Human Genetics, 2012, Vanderbilt University

URL: http://hdl.handle.net/1803/10702 

The activity of polymerase ã (pol ã) is complicated. To understand how its kinetics values affect the final function of the pol ã, I created a stochastic model of pol ã replication on the single nucleotide incorporation level. Using this model, I analyzed replication pauses of both wild-type and pathogenic mutated pol ã and discovered that the pausing time is proportional to the number of disassociations occurring in each forward step of the pol ã, and studied mitochondrial toxicity caused by nucleoside analogs in antiretroviral treatment. To enrich the yield of rare disease alleles, a probability-based approach, SampleSeq, has been developed to select samples for a targeted resequencing experiment that outperforms over sampling based on genotypes at associated SNPs from GWAS data. To detect somatic mutations, novel algorithms have been developed to detect base substitution and loss of heterozygosity, using next-generation sequencing data for normal-tumor sample pairs. Advisors/Committee Members: Todd I. Edwards (committee member), Ellen H. Fanning (committee member), William S. Bush (committee member), C. William Wester (committee member), Chun Li (Committee Chair), David C. Samuels (Committee Chair).

Subjects/Keywords: tumor somatic mutations; targeted sequencing; NRTI; polymerase gamma; mtDNA replication

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Song, Z. (2012). Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10702

Chicago Manual of Style (16th Edition):

Song, Zhuo. “Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed January 22, 2021. http://hdl.handle.net/1803/10702.

MLA Handbook (7th Edition):

Song, Zhuo. “Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.” 2012. Web. 22 Jan 2021.

Vancouver:

Song Z. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1803/10702.

Council of Science Editors:

Song Z. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/10702

2. Youssef, Sarah Hisham Abdelaziz. Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia.

Degree: MS, Pharmaceutical Sciences, 2018, University of Tennessee Health Science Center

URL: https://dc.uthsc.edu/dissertations/458 

Despite the improved outcome associated with current treatment strategies ofpediatric acute lymphoblastic leukemia (ALL), relapse still represents a major challenge. Pediatric ALL demonstrates branched evolution in response to selective pressure exerted by therapy; relapse founder clones emerge from pre-leukemic clones or minor subclones present at diagnosis. It is hence crucial to develop biomarkers capable of tracking subclones throughout therapy. Current practices for monitoring disease response in leukemia rely on the analysis of BM biopsy sample at specific time points throughout therapy. Not only the invasiveness of the BM biopsy hinders the sequential sampling, but also, the currently implied techniques are associated with a lack of sensitivity to detect subclones other than the major diagnostic clone. Somatic mutation detection in circulating-tumor DNA (Ct-DNA) offers a new venue for non-invasive studying of genetic heterogeneity and tracking clonal dynamics throughout therapy. Here, we employ targeted Next-Generation Sequencing (NGS) using a specifically designed ALL custom gene panel for Ct-DNA analysis of sequential plasma samples of 14 pediatric ALL during remission induction therapy. Utilizing 1 ml of plasma, Ct-DNA successfully captured all the clinically relevant somatic single nucleotide variants (SNVs) detected by whole exome sequencing (WES) in bone marrow (BM) biopsy samples at diagnosis. Moreover, we were able to show the ability of Ct-DNA analysis to track the change in the mutant allele fraction (MAF) across multiple time points as well as, to detect mutations in Flowcytometry (FC) MRD-negative patients. Taken together, sequential analysis of Ct-DNA in plasma demonstrates a role, as a non-invasive technique, for detecting the clonal composition as well as, tracking clonal dynamics in pediatric ALL. Advisors/Committee Members: Charles Gawad, MD, Ph.D..

Subjects/Keywords: Acute Lymphoblastic Leukemia; Circulating-tumor DNA (Ct-DNA); Clonal Dynamics; Leukemia-derived Circulating DNA; Pediatrics; Somatic Mutations; Medical Genetics; Medical Molecular Biology; Medical Sciences; Medicine and Health Sciences; Pharmacy and Pharmaceutical Sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Youssef, S. H. A. (2018). Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia. (Thesis). University of Tennessee Health Science Center. Retrieved from https://dc.uthsc.edu/dissertations/458

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Youssef, Sarah Hisham Abdelaziz. “Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia.” 2018. Thesis, University of Tennessee Health Science Center. Accessed January 22, 2021. https://dc.uthsc.edu/dissertations/458.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Youssef, Sarah Hisham Abdelaziz. “Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia.” 2018. Web. 22 Jan 2021.

Vancouver:

Youssef SHA. Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia. [Internet] [Thesis]. University of Tennessee Health Science Center; 2018. [cited 2021 Jan 22]. Available from: https://dc.uthsc.edu/dissertations/458.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Youssef SHA. Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia. [Thesis]. University of Tennessee Health Science Center; 2018. Available from: https://dc.uthsc.edu/dissertations/458

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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