Scientific Publications

Wisdom of crowds for robust gene network inference.

Publication TypeJournal Article
AuthorsMarbach, D., Costello JC, Küffner R., Vega NM, Prill RJ, Camacho DM, Allison KR, The DREAM5 Consortium, Aderhold A., Allison KR, Bonneau R., Camacho DM, Chen Y., Collins JJ, Cordero F., Costello JC, Crane M., Dondelinger F., Drton M., Esposito R., Foygel R., de la Fuente A., Gertheiss J., Geurts P., Greenfield A., Grzegorczyk M., Haury AC, Holmes B., Hothorn T., Husmeier D., Huynh-Thu VA, Irrthum A., Kellis M., Karlebach G., Küffner R., Lèbre S., De Leo V., Madar A., Mani S., Marbach D., Mordelet F., Ostrer H., Ouyang Z., Pandya R., Petri T., Pinna A., Poultney CS, Prill RJ, Rezny S., Ruskin HJ, Saeys Y., Shamir R., Sîrbu A., Song M., Soranzo N., Statnikov A., Stolovitzky G., Vega N., Vera-Licona P., Vert JP, Visconti A., Wang H., Wehenkel L., Windhager L., Zhang Y., Zimmer R., Kellis M., Collins JJ, and Stolovitzky G.
AbstractReconstructing 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.
Year of Publication2012
JournalNature methods
Date Published (YYYY/MM/DD)2012/07/15
ISSN Number1548-7091