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Nat Methods DOI:10.1038/nmeth.2016

Wisdom of crowds for robust gene network inference.

Publication TypeJournal Article
Year of Publication2012
AuthorsMarbach, D, Costello, JC, Küffner, R, Vega, NM, Prill, RJ, Camacho, DM, Allison, KR, Kellis, M, Collins, JJ, Stolovitzky, G
Corporate AuthorsDREAM5 Consortium
JournalNat Methods
Date Published2012 Jul 15
KeywordsAlgorithms, Computational Biology, Escherichia coli, Gene Expression Regulation, Bacterial, Gene Regulatory Networks, Oligonucleotide Array Sequence Analysis, Saccharomyces cerevisiae, Software, Staphylococcus aureus, Transcription, Genetic

Reconstructing gene regulatory networks from high-throughput data is a long-standing challenge. Through the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we performed a comprehensive blind assessment of over 30 network inference methods on Escherichia coli, Staphylococcus aureus, Saccharomyces cerevisiae and in silico microarray data. We characterize the performance, data requirements and inherent biases of different inference approaches, and we provide guidelines for algorithm application and development. We observed that no single inference method performs optimally across all data sets. In contrast, integration of predictions from multiple inference methods shows robust and high performance across diverse data sets. We thereby constructed high-confidence networks for E. coli and S. aureus, each comprising ~1,700 transcriptional interactions at a precision of ~50%. We experimentally tested 53 previously unobserved regulatory interactions in E. coli, of which 23 (43%) were supported. Our results establish community-based methods as a powerful and robust tool for the inference of transcriptional gene regulatory networks.


Alternate JournalNat. Methods
PubMed ID22796662
PubMed Central IDPMC3512113
Grant ListDP1 OD003644 / OD / NIH HHS / United States
R01 HG004037 / HG / NHGRI NIH HHS / United States
U54 CA132383 / CA / NCI NIH HHS / United States
U54CA121852 / CA / NCI NIH HHS / United States
DPI OD003644 / OD / NIH HHS / United States
U54 CA121852 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
U54CA132383 / CA / NCI NIH HHS / United States