Reverse engineering of regulatory networks in human B cells.
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.
Basso
Katia
K
Institute for Cancer Genetics, 1300 St. Nicholas Avenue, Room 912, New York, New York 10032, USA.
Margolin
Adam A
AA
Stolovitzky
Gustavo
G
Klein
Ulf
U
Dalla-Favera
Riccardo
R
Califano
Andrea
A
D000465:Algorithms; D001185:Artificial Intelligence; D001402:B-Lymphocytes / Q000378:metabolism*; D016000:Cluster Analysis; D003198:Computer Simulation; D030562:Databases, Protein; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018390:Gene Targeting / Q000379:methods; D016678:Genome; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D020543:Proteome / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D015398:Signal Transduction
D020543:Proteome; D016271:Proto-Oncogene Proteins c-myc