Integrating functional genomics, proteomics and computational analysis for the characterization of cellular networks

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Title: Integrating functional genomics, proteomics and computational analysis for the characterization of cellular networks
Author: Komurov, Kakajan
Abstract: As the study of biological systems progresses from a molecular level to a systems level , the development of new methodology for efficient data acquisition has been a key challenge of biological research in recent years . While development of novel high throughput experimental platforms is essential for an accurate large -scale data collection , novel theoretical methodology is indispensable for proper analysis and interpretation of these data . My projects aim at both , developing novel theoretic -analytical methodology for the analysis of functional patterns in biological networks , and also establishing a high throughput experimental platform for the study of signaling pathways . I have developed a generalized method for the analysis of functional organization in complex networks . This method makes use of several novel metrics used to characterize a node's status in the network . After the nodes are clustered according to their characteristics , statistically significant organizational patterns are revealed by random simulations of the network . Using this approach , I have found important characteristics of eukaryotic protein interaction networks that have direct implications in cellular phenomena like robustness and the efficiency of information processing . I have identified an entirely new class of functional modules with unique properties that contribute to the variability in cellular phenotypes . In addition , my analyses have uncovered a distinct pattern of organization in the protein network (called "rich club connectivity" ) that provides mechanistic explanations for some cell biological phenomena . This work not only reveals a highly organized functional dynamic layout of the protein interaction network , but also refines and /or corrects several notions proposed by previous studies . Functional genomic screens are a powerful tool for finding novel components of biological networks . However , in order to make these screens effective for assays that may require multiple readouts , it is necessary to channel the assay to another high throughput platform . Here , I used high throughput RNAi as a loss -of -function screen , and reverse -phase protein arrays as a high throughput readout
URI: http : / /hdl .handle .net /2152 .5 /671
Date: 2008-09-18

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Integrating functional genomics, proteomics and computational analysis for the characterization of cellular networks. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /671 .

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