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INTEGRATIVE APPROACH OF BIOLOGICAL SYSTEMS ANALYSIS ON REGULATORY PATHWAYS, MODULES, PROTEIN ESSENTIALITIES, AND DISEASE GENE CLASSIFICATION
by
Zhidong Tu
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(COMPUTATIONAL BIOLOGY AND BIOINFORMATICS)
December 2006
Copyright 2006 Zhidong Tu
Object Description
| Title | Integrative approach of biological systems analysis on regulatory pathways, modules, protein essentialities, and disease gene classification |
| Author | Tu, Zhidong |
| Author email | ztu@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Computational Biology & Bioinformatics |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2006-10-27 |
| Date submitted | 2006 |
| Restricted until | Unrestricted |
| Date published | 2006-11-15 |
| Advisor (committee chair) | Sun, Fengzhu |
| Advisor (committee member) |
Chen, Ting Arbeitman, Michelle N. Kempe, David |
| Abstract | The rapid development in high throughput biotechnologies in the last decade has fundamentally changed the way of studying biological systems. Today, whole genome sequences are either available or can be obtained within weeks. Genome wide expression levels can be easily measured by microarray analyses. Tens of thousands of protein-protein interactions have been identified in several species, by either yeast two hybrid assays or by mass spectrometry. Transcription factor-DNA binding interactions can also be identified by high throughput techniques, such as by chromatin immunoprecipitation followed by whole genome chip analyses. Many other new technologies are emerging, such as high throughput cell imaging, protein arrays. All these technologies, together with traditional methods, provide us an unprecedented opportunity to explore biological systems in a holistic way. Computational biologists are confronted with great opportunity but also significant challenges in analyzing these data sets to extract biologically meaningful knowledge. Since no single technique can provide all the information needed for understanding the system, integrative analysis has turned out to be an essential approach to unravel how the systems work.; We demonstrate how we pursued such integrative approaches by presenting the results of several independent but related problems. Specifically, we studied (i) causal gene inference and regulatory pathway identification, (ii) transcriptional module identification and its dynamics, (iii) essential protein prediction, and (iv) human disease gene classification. For the first two problems, we treated the system as a network of interactions and regulations and based our analysis mainly on this network. For the third problem, we used both network properties and several other features. For the last problem, we mainly relied on feature comparison.; We want to show from these analyses that the integrative approach can help us to better utilize data, to design more realistic models, and to achieve what would otherwise be impossible by any single data source. We anticipate that as increasingly more large scale data sets become available, our understanding of the systems will be significantly deepened. |
| Keyword | Systems biology; computational algorithm; data integration |
| 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-m149 |
| Rights | Tu, Zhidong |
| 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-Tu-20061115 |
| Archival file | uscthesesreloadpub_Volume44/etd-Tu-20061115.pdf |
Description
| Title | Page 1 |
| Full text | INTEGRATIVE APPROACH OF BIOLOGICAL SYSTEMS ANALYSIS ON REGULATORY PATHWAYS, MODULES, PROTEIN ESSENTIALITIES, AND DISEASE GENE CLASSIFICATION by Zhidong Tu A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (COMPUTATIONAL BIOLOGY AND BIOINFORMATICS) December 2006 Copyright 2006 Zhidong Tu |
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