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A HIERARCHICAL
PHYSOIOLOGICALLY-BASED PHARMACOKINETIC MODELING
PLATFORM FOR GENETIC AND EXPOSURE EFFECTS IN METABOLIC
PATHWAYS
by
Lingyun Du
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOSTATISTICS)
August 2007
Copyright 2007 Lingyun Du
Object Description
| Title | A hierarchical physiologically-based pharmacokinetic modeling platform for genetic and exposure effects in metabolic pathways |
| Author | Du, Lingyun |
| Author email | hellofromku@yahoo.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Biostatistics |
| School | Keck School of Medicine |
| Date defended/completed | 2007-01-16 |
| Date submitted | 2007 |
| Restricted until | Unrestricted |
| Date published | 2007-07-13 |
| Advisor (committee chair) | Thomas, Duncan |
| Advisor (committee member) |
Conti, David V. Watanabe, Richard |
| Abstract | Metabolic pathways are candidates for examining gene-exposure interaction effects on complex diseases. We present a hierarchical modeling platform integrating physiologically based pharmocokinetic models and Bayesian approaches to characterize gene-exposure interaction effects in a metabolic pathway. We simulate datasets under a known metabolic model. Individual-specific metabolic rates are described by Michaelis-Menten parameters Vmax and Km, regressed on genotypes at the relevant loci. Intermediate measurements such as enzyme activities and metabolite concentrations are incorporated as flawed measurements of an individual's long-term metabolic rates and metabolite concentrations. Parameter posteriors are estimated using Markov Chain Monte Carlo methods. The platform allows investigation posterior estimation precision relative to the simulated effect magnitude and appears to have great utility for characterizing etiologic genetic and exposure effects and dissecting complex pathways. |
| Keyword | metabolic pathways; physiologically based pharmacokinetic models; Bayesian approaches; hierarchical modeling; exposure; genotype; Michaelis-Menten; intermediate measurements; enzyme activities; metabolite concentrations; Markov chain Monte Carlo |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m618 |
| Rights | Du, Lingyun |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Du-20070713 |
| Archival file | uscthesesreloadpub_Volume44/etd-Du-20070713.pdf |
Description
| Title | Page 1 |
| Full text | A HIERARCHICAL PHYSOIOLOGICALLY-BASED PHARMACOKINETIC MODELING PLATFORM FOR GENETIC AND EXPOSURE EFFECTS IN METABOLIC PATHWAYS by Lingyun Du A Thesis Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (BIOSTATISTICS) August 2007 Copyright 2007 Lingyun Du |
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