To provide accurate biological hypotheses and elucidate global properties of cellular networks, systematic identification of protein-protein interactions must meet high quality standards. We present an expanded C. elegans protein-protein interaction network, or 'interactome' map, derived from testing a matrix of ∼10,000 × ∼10,000 proteins using a highly specific, high-throughput yeast two-hybrid system. Through a new empirical quality control framework, we show that the resulting data set (Worm Interactome 2007, or WI-2007) was similar in quality to low-throughput data curated from the literature. We filtered previous interaction data sets and integrated them with WI-2007 to generate a high-confidence consolidated map (Worm Interactome version 8, or WI8). This work allowed us to estimate the size of the worm interactome at ∼116,000 interactions. Comparison with other types of functional genomic data shows the complementarity of distinct experimental approaches in predicting different functional relationships between genes or proteins.
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We thank F. Piano and members of the Cancer Center for System Biology and the Vidal laboratory for discussions, A. Petcherski from WormBase for assistance with worm genetic interactions, and Z. Hu for VisANT assistance. The worm interactome project was supported by grants from the US National Institutes of Health—R01 HG001715 (M.V. and F.P.R.), R01 HG003224 (F.P.R.), F32 HG004098 (M. Tasan), T32 CA09361 (K.V.)—a University of Ghent grant GOA12051401 (J.T.), and the Fonds Wetenschappelijk Onderzoek – Vlaanderen (FWO-V) G.0031.06 (J.T.). I.L. was supported by a postdoctoral fellowship from the FWO-V. K.C.G. and H.-L.K. were supported by US Department of the Army Award W81XWH-04-1-0307 and the State of New York's Science and Tech Resources contract C040066. M.V. is a Chercheur Qualifié Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium).
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