Reverse engineering of regulatory networks in human B cells

Katia Basso, Adam A. Margolin, Gustavo Stolovitzky, Ulf Klein, Riccardo Dalla-Favera, Andrea Califano

Research output: Contribution to journalArticle

978 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)382-390
Number of pages9
JournalNature genetics
Volume37
Issue number4
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Basso, K., Margolin, A. A., Stolovitzky, G., Klein, U., Dalla-Favera, R., & Califano, A. (2005). Reverse engineering of regulatory networks in human B cells. Nature genetics, 37(4), 382-390. https://doi.org/10.1038/ng1532