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A Map of the Interactome Network of the Metazoan C. elegans Science, Vol 303, 540-543, 23 January 2004 • how protein-protein interaction (or "interactome") networks relate to multicellular functions • The yeast Saccharomyces cerevisiae : develop a eukaryotic unicellular interactome map. • Caenorhabditis elegans : studying how protein networks relate to multicellularity. • Investigate its interactome network with HT-Y2H. • Y2H system • bioinformatics criteria • coaffinity purification (co-AP) glutathione S-transferase (GST) pull-down assay • more than 4000 interactions were identified from high-throughput, yeast twohybrid (HT=Y2H) screens • the Worm Interactome (WI5) map contains 5500 interactions Coaffinity purification assays Decision tree used to assign a confidence level to Y2H interactions. Analysis of the WI5 network Overlap with transcriptome The dash-circled proteins belong to the same paralogous family (sharing more than 80% homology) In S. cerevisiae, two proteins that have many interaction partners in common are more likely to be related biologically • These data demonstrate that their three data sets contain a large proportion of highly reliable interactions and corroborate their expected relative qualities. • Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses.