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Open Access Research article

Composite functional module inference: detecting cooperation between transcriptional regulation and protein interaction by mantel test

Chao Wu1, Fan Zhang1, Xia Li1*, Shihua Zhang1, Jiang Li1, Fei Su1, Kongning Li1 and Yuqing Yan2

Author Affiliations

1 Department of Bioinformatics and Bio-pharmaceutical Key Laboratory of Heilongjiang Province and State, Harbin Medical University, Harbin, Heilongjiang 150086, China

2 Department of Genetics and Genome Biology, University of Toronto, Toronto, Ontario, Canada

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BMC Systems Biology 2010, 4:82  doi:10.1186/1752-0509-4-82

Published: 10 June 2010



Functional modules are basic units of cell function, and exploring them is important for understanding the organization, regulation and execution of cell processes. Functional modules in single biological networks (e.g., the protein-protein interaction network), have been the focus of recent studies. Functional modules in the integrated network are composite functional modules, which imply the complex relationships involving multiple biological interaction types, and detect them will help us understand the complexity of cell processes.


We aimed to detect composite functional modules containing co-transcriptional regulation interaction, and protein-protein interaction, in our pre-constructed integrated network of Saccharomyces cerevisiae. We computationally extracted 15 composite functional modules, and found structural consistency between co-transcriptional regulation interaction sub-network and protein-protein interaction sub-network that was well correlated with their functional hierarchy. This type of composite functional modules was compact in structure, and was found to participate in essential cell processes such as oxidative phosphorylation and RNA splicing.


The structure of composite functional modules containing co-transcriptional regulation interaction, and protein-protein interaction reflected the cooperation of transcriptional regulation and protein function implementation, and was indicative of their important roles in essential cell functions. In addition, their structural and functional characteristics were closely related, and suggesting the complexity of the cell regulatory system.