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

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.The inference of gene regulatory networks from gene expression data is crucial for enhancing our understanding about relations between genes [1-3]. In general, a gene network describes a map of direct physical (biochemical) interactions among genes, gene products or metabolites that occur in the living cell [4,5] and, hence, enable a systems biology approach [6-8]. It has been demonstrated that gene regulatory networks, as a specific type thereof, can be indirectly inferred from steady state gene expression data, which are measured under different conditions either in individual tissues or cell types [9-11].In general, it is believed that the gene regulatory network is governed by major hub genes like transcription factors that directly bind specific DNA segments in the nucleus and activate or repress the expression of other genes [1,12]. Further, it has been proposed that the genes in cellular networks are organize