Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy
Journal
BMC Systems Biology
Journal Volume
4
Pages
138
Date Issued
2010
Author(s)
Abstract
Background: Molecular networks represent the backbone of molecular activity within cells and provide opportunities for understanding the mechanism of diseases. While protein-protein interaction data constitute static network maps, integration of condition-specific co-expression information provides clues to the dynamic features of these networks. Dilated cardiomyopathy is a leading cause of heart failure. Although previous studies have identified putative biomarkers or therapeutic targets for heart failure, the underlying molecular mechanism of dilated cardiomyopathy remains unclear.Results: We developed a network-based comparative analysis approach that integrates protein-protein interactions with gene expression profiles and biological function annotations to reveal dynamic functional modules under different biological states. We found that hub proteins in condition-specific co-expressed protein interaction networks tended to be differentially expressed between biological states. Applying this method to a cohort of heart failure patients, we identified two functional modules that significantly emerged from the interaction networks. The dynamics of these modules between normal and disease states further suggest a potential molecular model of dilated cardiomyopathy.Conclusions: We propose a novel framework to analyze the interaction networks in different biological states. It successfully reveals network modules closely related to heart failure; more importantly, these network dynamics provide new insights into the cause of dilated cardiomyopathy. The revealed molecular modules might be used as potential drug targets and provide new directions for heart failure therapy. ? 2010 Lin et al; licensee BioMed Central Ltd.
SDGs
Other Subjects
protein; article; congestive cardiomyopathy; disease course; gene expression profiling; genetics; heart failure; human; metabolism; molecular genetics; pathology; protein analysis; protein binding; Cardiomyopathy, Dilated; Disease Progression; Gene Expression Profiling; Heart Failure; Humans; Molecular Sequence Annotation; Protein Binding; Protein Interaction Mapping; Proteins
Type
journal article