رسالة جامعية

Integrative Analysis of Genomic and Transcriptomic Data in Taiwanese Lung Adenocarcinomas

التفاصيل البيبلوغرافية
العنوان: Integrative Analysis of Genomic and Transcriptomic Data in Taiwanese Lung Adenocarcinomas
المؤلفون: Ho, Hao
المساهمون: Li, Ker-Chau
بيانات النشر: eScholarship, University of California
سنة النشر: 2017
المجموعة: University of California: eScholarship
مصطلحات موضوعية: Statistics, Bioinformatics, copy number alteration, gene regulation, liquid association, lung adenocarcinoma, miRNA expression, somatic mutation
الوصف: In this thesis, we studied genomic and transcriptomic data from over 300 Taiwanese lung cancer patients. For structural variation analysis, we proposed a workflow to detect inter-chromosomal structural variation using whole genome sequencing data and introduced an integrated ESP plot for the visualization. We studied somatic DNA alterations and constructed a comprehensive landscape in Taiwanese lung adenocarcinomas by whole exome sequencing and array CGH data. At the single nucleotide level, we identified non-synonymous recurrent point mutations using a binomial probability model. The potential clinical relevance was demonstrated by a survival analysis of patients' relapse-free survival. Mutation variant allele frequency was integrated for improving prognosis power. When exploring the potential downstream, we identified a miRNA expression correlated with these recurrent point mutations. In the study of differential gene expressions between EGFR mutant and wild-type tumors. We derived a statistical framework that combines differential expression analysis and differential regulation analysis to form an enrichment test for identifying critical regulator on the cis-regulatory network. A modified liquid association was introduced for quantifying the change of co-variations in the differential regulation analysis. By integrating copy number, miRNA expression and gene expression data, several key regulators and their cis-targets were identified and visualized together as a network. For a statistical issue of liquid association, we discussed the effects of ignoring background variables to the liquid association scoring method and proposed adjustment methods to marginalize their influence.
نوع الوثيقة: thesis
وصف الملف: application/pdf
اللغة: English
العلاقة: qt8n08589r; https://escholarship.org/uc/item/8n08589rTest
الإتاحة: https://escholarship.org/uc/item/8n08589rTest
حقوق: public
رقم الانضمام: edsbas.677ECC68
قاعدة البيانات: BASE