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 |