Reverse engineering of regulatory networks in human B cells
Top Cited Papers
- 20 March 2005
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 37 (4), 382-390
- https://doi.org/10.1038/ng1532
Abstract
Cellular phenotypes are determined by the differential activity of networks linking coregulated genes. Available methods for the reverse engineering of such networks from genome-wide expression profiles have been successful only in the analysis of lower eukaryotes with simple genomes. Using a new method called ARACNe (algorithm for the reconstruction of accurate cellular networks), we report the reconstruction of regulatory networks from expression profiles of human B cells. The results are suggestive a hierarchical, scale-free network, where a few highly interconnected genes (hubs) account for most of the interactions. Validation of the network against available data led to the identification of MYC as a major hub, which controls a network comprising known target genes as well as new ones, which were biochemically validated. The newly identified MYC targets include some major hubs. This approach can be generally useful for the analysis of normal and pathologic networks in mammalian cells.Keywords
This publication has 45 references indexed in Scilit:
- Tracking CD40 signaling during germinal center developmentBlood, 2004
- Conservation and Coevolution in the Scale-Free Human Gene Coexpression NetworkMolecular Biology and Evolution, 2004
- Evidence for dynamically organized modularity in the yeast protein–protein interaction networkNature, 2004
- Gene Expression Profiling of Hairy Cell Leukemia Reveals a Phenotype Related to Memory B Cells with Altered Expression of Chemokine and Adhesion ReceptorsThe Journal of Experimental Medicine, 2004
- BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B CellsThe Journal of Experimental Medicine, 2003
- A Large Scale Genetic Analysis of c-Myc-regulated Gene Expression PatternsJournal of Biological Chemistry, 2003
- Binding of c-Myc to chromatin mediates mitogen-induced acetylation of histone H4 and gene activationGenes & Development, 2001
- Using Bayesian Networks to Analyze Expression DataJournal of Computational Biology, 2000
- Functional Discovery via a Compendium of Expression ProfilesCell, 2000
- Germinal CentersAnnual Review of Immunology, 1994