Integrating Functional Genomics, Proteomics and Computational Analysis for the Characterization of Cellular Networks

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2008-09-18

Authors

Komurov, Kakajan

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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

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