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This article is part of the supplement: Selected articles from The 5th IEEE International Conference on Systems Biology (ISB 2011)

Open Access Open Badges Research

Inferring domain-domain interactions from protein-protein interactions in the complex network conformation

Chen Chen1, Jun-Fei Zhao1, Qiang Huang1, Rui-Sheng Wang2 and Xiang-Sun Zhang13*

Author Affiliations

1 Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, PR China

2 Department of Physics, Pennsylvania State University, University Park, PA 16802, USA

3 National Center for Mathematics and Interdisciplinary Sciences, Chinese Academy of Sciences, Beijing 100190, PR China

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BMC Systems Biology 2012, 6(Suppl 1):S7  doi:10.1186/1752-0509-6-S1-S7

Published: 16 July 2012



As protein domains are functional and structural units of proteins, a large proportion of protein-protein interactions (PPIs) are achieved by domain-domain interactions (DDIs), many computational efforts have been made to identify DDIs from experimental PPIs since high throughput technologies have produced a large number of PPIs for different species. These methods can be separated into two categories: deterministic and probabilistic. In deterministic methods, parsimony assumption has been utilized. Parsimony principle has been widely used in computational biology as the evolution of the nature is considered as a continuous optimization process. In the context of identifying DDIs, parsimony methods try to find a minimal set of DDIs that can explain the observed PPIs. This category of methods are promising since they can be formulated and solved easily. Besides, researches have shown that they can detect specific DDIs, which is often hard for many probabilistic methods. We notice that existing methods just view PPI networks as simply assembled by single interactions, but there is now ample evidence that PPI networks should be considered in a global (systematic) point of view for it exhibits general properties of complex networks, such as 'scale-free' and 'small-world'.


In this work, we integrate this global point of view into the parsimony-based model. Particularly, prior knowledge is extracted from these global properties by plausible reasoning and then taken as input. We investigate the role of the added information extensively through numerical experiments. Results show that the proposed method has improved performance, which confirms the biological meanings of the extracted prior knowledge.


This work provides us some clues for using these properties of complex networks in computational models and to some extent reveals the biological meanings underlying these general network properties.