Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy.
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.
Lin
Chen-Ching
CC
Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.
Hsiang
Jen-Tsung
JT
Wu
Chia-Yi
CY
Oyang
Yen-Jen
YJ
Juan
Hsueh-Fen
HF
Huang
Hsuan-Cheng
HC
D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058977:Molecular Sequence Annotation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*
D011506:Proteins