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Organizational structure and the periphery of the gene regulatory network in B-cell lymphoma

Ricardo de Matos Simoes, Shailesh Tripathi and Frank Emmert-Streib*

Author Affiliations

Computational Biology and Machine Learning Lab, Center for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK

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BMC Systems Biology 2012, 6:38  doi:10.1186/1752-0509-6-38

Published: 14 May 2012



The physical periphery of a biological cell is mainly described by signaling pathways which are triggered by transmembrane proteins and receptors that are sentinels to control the whole gene regulatory network of a cell. However, our current knowledge about the gene regulatory mechanisms that are governed by extracellular signals is severely limited.


The purpose of this paper is three fold. First, we infer a gene regulatory network from a large-scale B-cell lymphoma expression data set using the C3NET algorithm. Second, we provide a functional and structural analysis of the largest connected component of this network, revealing that this network component corresponds to the peripheral region of a cell. Third, we analyze the hierarchical organization of network components of the whole inferred B-cell gene regulatory network by introducing a new approach which exploits the variability within the data as well as the inferential characteristics of C3NET. As a result, we find a functional bisection of the network corresponding to different cellular components.


Overall, our study allows to highlight the peripheral gene regulatory network of B-cells and shows that it is centered around hub transmembrane proteins located at the physical periphery of the cell. In addition, we identify a variety of novel pathological transmembrane proteins such as ion channel complexes and signaling receptors in B-cell lymphoma.

B-cell lymphoma; Gene expression data; Gene regulatory network; Statistical network inference