Reverse engineering cellular networks

Adam Margolin, Kai Wang, Wei Keat Lim, Manjunath Kustagi, Ilya Nemenman, Andrea Califano

Research output: Contribution to journalArticle

241 Citations (Scopus)

Abstract

We describe a computational protocol for the ARACNE algorithm, an information-theoretic method for identifying transcriptional interactions between gene products using microarray expression profile data. Similar to other algorithms, ARACNE predicts potential functional associations among genes, or novel functions for uncharacterized genes, by identifying statistical dependencies between gene products. However, based on biochemical validation, literature searches and DNA binding site enrichment analysis, ARACNE has also proven effective in identifying bona fide transcriptional targets, even in complex mammalian networks. Thus we envision that predictions made by ARACNE, especially when supplemented with prior knowledge or additional data sources, can provide appropriate hypotheses for the further investigation of cellular networks. While the examples in this protocol use only gene expression profile data, the algorithm's theoretical basis readily extends to a variety of other high-throughput measurements, such as pathway-specific or genome-wide proteomics, microRNA and metabolomics data. As these data become readily available, we expect that ARACNE might prove increasingly useful in elucidating the underlying interaction models. For a microarray data set containing ∼10,000 probes, reconstructing the network around a single probe completes in several minutes using a desktop computer with a Pentium 4 processor. Reconstructing a genome-wide network generally requires a computational cluster, especially if the recommended bootstrapping procedure is used.

Original languageEnglish (US)
Pages (from-to)662-671
Number of pages10
JournalNature Protocols
Volume1
Issue number2
DOIs
StatePublished - Jul 2006
Externally publishedYes

Fingerprint

Cell Engineering
Reverse engineering
Genes
Genome
Microarrays
Metabolomics
Information Storage and Retrieval
MicroRNAs
Transcriptome
Proteomics
Network protocols
Binding Sites
Complex networks
Gene expression
Personal computers
DNA
Throughput

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Margolin, A., Wang, K., Lim, W. K., Kustagi, M., Nemenman, I., & Califano, A. (2006). Reverse engineering cellular networks. Nature Protocols, 1(2), 662-671. https://doi.org/10.1038/nprot.2006.106

Reverse engineering cellular networks. / Margolin, Adam; Wang, Kai; Lim, Wei Keat; Kustagi, Manjunath; Nemenman, Ilya; Califano, Andrea.

In: Nature Protocols, Vol. 1, No. 2, 07.2006, p. 662-671.

Research output: Contribution to journalArticle

Margolin, A, Wang, K, Lim, WK, Kustagi, M, Nemenman, I & Califano, A 2006, 'Reverse engineering cellular networks', Nature Protocols, vol. 1, no. 2, pp. 662-671. https://doi.org/10.1038/nprot.2006.106
Margolin A, Wang K, Lim WK, Kustagi M, Nemenman I, Califano A. Reverse engineering cellular networks. Nature Protocols. 2006 Jul;1(2):662-671. https://doi.org/10.1038/nprot.2006.106
Margolin, Adam ; Wang, Kai ; Lim, Wei Keat ; Kustagi, Manjunath ; Nemenman, Ilya ; Califano, Andrea. / Reverse engineering cellular networks. In: Nature Protocols. 2006 ; Vol. 1, No. 2. pp. 662-671.
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