Discovering distinct functional modules of specific cancer types using protein-protein interaction networks.
BACKGROUND
The molecular profiles exhibited in different cancer types are very different; hence, discovering distinct functional modules associated with specific cancer types is very important to understand the distinct functions associated with them. Protein-protein interaction networks carry vital information about molecular interactions in cellular systems, and identification of functional modules (subgraphs) in these networks is one of the most important applications of biological network analysis.


RESULTS
In this study, we developed a new graph theory based method to identify distinct functional modules from nine different cancer protein-protein interaction networks. The method is composed of three major steps: (i) extracting modules from protein-protein interaction networks using network clustering algorithms; (ii) identifying distinct subgraphs from the derived modules; and (iii) identifying distinct subgraph patterns from distinct subgraphs. The subgraph patterns were evaluated using experimentally determined cancer-specific protein-protein interaction data from the Ingenuity knowledgebase, to identify distinct functional modules that are specific to each cancer type.


CONCLUSIONS
We identified cancer-type specific subgraph patterns that may represent the functional modules involved in the molecular pathogenesis of different cancer types. Our method can serve as an effective tool to discover cancer-type specific functional modules from large protein-protein interaction networks.
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Ru
R
Shen
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Xiaosheng
X
Wang
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA ; Bioinformatics and Systems Biology Core, University of Nebraska Medical Center, Omaha, NE 68198, USA ; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA ; Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Chittibabu
C
Guda
D000465:Algorithms; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000145:classification* / Q000378:metabolism*; D025941:Protein Interaction Mapping / Q000379:methods*; D060066:Protein Interaction Maps / Q000502:physiology*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins