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Integrating Gene Expression and Metabolic Profiles*

Zheng Li,C. Chan

Published 2004 in Journal of Biological Chemistry

ABSTRACT

Recent advances in high throughput technologies have generated an abundance of biological information, such as gene expression, protein-protein interaction, and metabolic data. These various types of data capture different aspects of the cellular response to environmental factors. Integrating data from different measurements enhances the ability of modeling frameworks to predict cellular function more accurately and can lead to a more coherent reconstruction of the underlying regulatory network structure. Different techniques, newly developed and borrowed, have been applied for the purpose of extracting this information from experimental data. In this study, we developed a framework to integrate metabolic and gene expression profiles for a hepatocellular system. Specifically, we applied genetic algorithm and partial least square analysis to identify important genes relevant to a specific cellular function. We identified genes 1) whose expression levels quantitatively predict a metabolic function and 2) that play a part in regulating a hepatocellular function and reconstructed their role in the metabolic network. The framework 1) preprocesses the gene expression data using statistical techniques, 2) selects genes using a genetic algorithm and couples them to a partial least squares analysis to predict cellular function, and 3) reconstructs, with the assistance of a literature search, the pathways that regulate cellular function, namely intracellular triglyceride and urea synthesis. This provides a framework for identifying cellular pathways that are active as a function of the environment and in turn helps to uncover the interplay between gene and metabolic networks.

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