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Open Access Highly Accessed Research article

Investigating the validity of current network analysis on static conglomerate networks by protein network stratification

Minlu Zhang12 and Long J Lu1234*

Author Affiliations

1 Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA

2 Department of Computer Science, University of Cincinnati, 2600 Clifton Avenue, Cincinnati, Ohio 45221, USA

3 Department of Biomedical Engineering, University of Cincinnati, 2600 Clifton Avenue, Cincinnati, Ohio 45221, USA

4 Department of Environmental Health, University of Cincinnati, 2600 Clifton Avenue, Cincinnati, Ohio 45221, USA

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BMC Bioinformatics 2010, 11:466  doi:10.1186/1471-2105-11-466

Published: 16 September 2010



A molecular network perspective forms the foundation of systems biology. A common practice in analyzing protein-protein interaction (PPI) networks is to perform network analysis on a conglomerate network that is an assembly of all available binary interactions in a given organism from diverse data sources. Recent studies on network dynamics suggested that this approach might have ignored the dynamic nature of context-dependent molecular systems.


In this study, we employed a network stratification strategy to investigate the validity of the current network analysis on conglomerate PPI networks. Using the genome-scale tissue- and condition-specific proteomics data in Arabidopsis thaliana, we present here the first systematic investigation into this question. We stratified a conglomerate A. thaliana PPI network into three levels of context-dependent subnetworks. We then focused on three types of most commonly conducted network analyses, i.e., topological, functional and modular analyses, and compared the results from these network analyses on the conglomerate network and five stratified context-dependent subnetworks corresponding to specific tissues.


We found that the results based on the conglomerate PPI network are often significantly different from those of context-dependent subnetworks corresponding to specific tissues or conditions. This conclusion depends neither on relatively arbitrary cutoffs (such as those defining network hubs or bottlenecks), nor on specific network clustering algorithms for module extraction, nor on the possible high false positive rates of binary interactions in PPI networks. We also found that our conclusions are likely to be valid in human PPI networks. Furthermore, network stratification may help resolve many controversies in current research of systems biology.