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A map of the interactome network of the metazoan C. elegans

Siming Li et al. Science. .

Abstract

To initiate studies on how protein-protein interaction (or "interactome") networks relate to multicellular functions, we have mapped a large fraction of the Caenorhabditis elegans interactome network. Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. Independent coaffinity purification assays experimentally validated the overall quality of this Y2H data set. Together with already described Y2H interactions and interologs predicted in silico, the current version of the Worm Interactome (WI5) map contains approximately 5500 interactions. Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses.

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Figures

Fig. 1
Fig. 1
Coaffinity purification assays. Shown are 10 examples from the Core-1, Core-2, and Non-Core data sets. The top panels show Myc-tagged prey expression after affinity purification on glutathione-Sepharose, demonstrating binding to GST-bait. The middle and bottom panels show expression of Myc-prey and GST-bait, respectively. The lanes alternate between extracts expressing GST-bait proteins (+) and GST alone (-). ORF pairs are identified in table S1 with the lane number corresponding to the order in which they appear in the table.
Fig.2
Fig.2
Analysis of the WI5 network. (A) Nodes (representing proteins) are colored according to their phylogenic class: ancient (red), multicellular (yellow), and worm (blue). Edges represent protein-protein interactions. The inset highlights a small part of the network. (B) The proportion of proteins, P(k), with different numbers of interacting partners, k, is shown for C. elegans proteins used as baits or preys and for S. cerevisiae proteins. (C) The pie charts show the proportion of interacting preys found in Y2H screens that fall into each phylogenic class. Also shown is the distribution of all preys found and all preys searched in the AD-ORFeome1.0 library. (D) Overlap with transcriptome (see text) (18), Pearson correlation coefficients (PCCs) were calculated and graphed for each pair of proteins in the interaction data sets and their corresponding randomized data sets. The red area to the right corresponds to interactions that show a significant relationship to expression profiling data (P < 0.05). (E) Interactions between proteins in Topomap mountain 29 (18). The dash-circled proteins belong to the same paralogous family (sharing more than 80% homology) and are thus collapsed into one set of interactions. (F) Proportion of interaction pairs where both genes are embryonic lethal (P < 10-7).
Fig.3
Fig.3
Graphical representation of a highly interconnected subnetwork around VAB-3 and C49A1.4. Biological functional classes were obtained from WormPD (10).
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