Global networks of functional coupling in eukaryotes from comprehensive data integration
Abstract
No single experimental method can discover all connections in the interactome. A computational approach can help by integrating data from multiple, often unrelated, proteomics and genomics pipelines. Reconstructing global networks of functional coupling (FC) faces the challenges of scale and heterogeneity - how to efficiently integrate huge amounts of diverse data from multiple organisms, yet ensuring high accuracy? We developed FunCoup, an optimized Bayesian framework, to resolve these issues. Because interactomes comprise functional coupling of many types, FunCoup annotates network edges with confidence scores in support of different kinds of interactions: physical interaction, protein complex member, metabolic or signaling link. This capability boosted overall accuracy. On the whole, the constructed framework was comprehensively tested to optimize the overall confidence and ensure seamless, automated incorporation of new data sets of heterogeneous types. Using over 50 datasets in seven organisms, and extensively transferring information between orthologs, FunCoup predicted global networks in eight eukaryotes. For the Ciona intestinalis network only orthologous information was used, and it recovered a significant number of experimental facts. FunCoup predictions were validated on independent cancer mutation data. We show how FunCoup can be used for discovering candidate members of the Parkinson and Alzheimer pathways. Cross-species pathway conservation analysis provided further support to these observations. The networks, which are the largest interactome reconstructions to date, are freely available for download and query at http://FunCoup.sbc.su.se. The site allows detailed graphical and tabular analysis of subnetworks around query genes, as well as comparative analysis of orthologous networks in multiple species.
Footnotes
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- Received October 1, 2008.
- Accepted February 19, 2009.
- Copyright © 2009, Cold Spring Harbor Laboratory Press
