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Empirically controlled mapping of the Caenorhabditis elegans protein-protein interactome network

Abstract

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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Figure 1: Construction and characterization of WI-2007.
Figure 2: WI8: an extended, high-quality, protein-protein interaction network.
Figure 3: Biological relevance.
Figure 4: Examples of multiple-evidence subnetworks.

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Acknowledgements

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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Contributions

J.-F.R., N.S. and A.-R.C. coordinated experiments and data analysis. J.-F.R., T.H.-K., J.M.S., F.G., S.C., P.B., N.L., N.A.-G., E.D., D.S., A.D., C.S., M.V., H.Y., M.B., S.M., M.D., M. Tewari and J.S.A. performed the high-throughput ORF cloning and Y2H screens. I.L., A.-S.d.S., P.B. and J.T. conducted the MAPPIT experiments. N.S., A.-R.C., M. Tasan, T.H., N.K., K.V., C.F., N.B., M.A.Y., C.L., A.S., H.-L.K. and K.C.G. performed the computational analyses. M. Tasan, N.S., C.F., A.-R.C., H.-L.K. and K.C.G. adapted or built the website and visualization tools. N.S., A.-R.C., J.-F.R., M.E.C., J.V., F.P.R. and M.V. wrote the manuscript. M.V. conceived the project. D.E.H., J.T., F.P.R. and M.V. co-directed the project.

Corresponding authors

Correspondence to David E Hill or Jan Tavernier or Frederick P Roth or Marc Vidal.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5, Supplementary Tables 1–5, Supplementary Discussion, Supplementary Methods (PDF 987 kb)

Supplementary Data 1

WI8 MIMIX (TXT 2857 kb)

Supplementary Data 2

Integrated functional network (TXT 7021 kb)

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Simonis, N., Rual, JF., Carvunis, AR. et al. Empirically controlled mapping of the Caenorhabditis elegans protein-protein interactome network. Nat Methods 6, 47–54 (2009). https://doi.org/10.1038/nmeth.1279

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