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Cost-effective strategies for completing the interactome

Nature Methods volume 6, pages 55–61 (2009)Cite this article

Abstract

Comprehensive protein-interaction mapping projects are underway for many model species and humans. A key step in these projects is estimating the time, cost and personnel required for obtaining an accurate and complete map. Here we modeled the cost of interaction-map completion for various experimental designs. We showed that current efforts may require up to 20 independent tests covering each protein pair to approach completion. We explored designs for reducing this cost substantially, including prioritization of protein pairs, probability thresholding and interaction prediction. The best experimental designs lowered cost by fourfold overall and >100-fold in early stages of mapping. We demonstrate the best strategy in an ongoing project in Drosophila melanogaster, in which we mapped 450 high-confidence interactions using 47 microtiter plates, versus thousands of plates expected using current designs. This study provides a framework for assessing the feasibility of interaction mapping projects and for future efforts to increase their efficiency.

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Figure 1: Simulating an interaction mapping project.
Figure 2: Analysis of the coverage and saturation of the fly interactome as a function of the number of independent screens.
Figure 3: Fly and human interactome coverage costs for different experimental strategies.
Figure 4: Design and implementation of the prediction strategy for mapping the interactome.

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Acknowledgements

We thank S. Bandyopadhyay for critical reading of the manuscript, I. Bronner, K. Gulyas, B. Mangiola and H. Zhang for expert technical assistance with the two-hybrid assays, and R. Karp and R. Sharan for discussions of earlier versions of this work. This work was supported by US National Institutes of Health grants RR018627, GM070743 and HG001536.

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Authors and Affiliations

  1. Department of Bioengineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, 92093, California, USA

    Ariel S Schwartz & Trey Ideker

  2. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, 48201, Michigan, USA

    Jingkai Yu, Kyle R Gardenour & Russell L Finley Jr

Authors
  1. Ariel S Schwartz
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  2. Jingkai Yu
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  3. Kyle R Gardenour
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Contributions

A.S.S. and T.I. formulated the probabilistic model and performed the simulations. J.Y., K.R.G. and R.L.F. generated all new reported Y2H data. A.S.S., R.L.F. and T.I. wrote the paper.

Corresponding author

Correspondence to Trey Ideker.

Supplementary information

Supplementary Text and Figures1

Supplementary Figure 1, Supplementary Tables 1–2, Supplementary Methods (PDF 525 kb)

Supplementary Data

Results from protein-protein interaction predictions in Drosophila. (XLS 575 kb)

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Schwartz, A., Yu, J., Gardenour, K. et al. Cost-effective strategies for completing the interactome. Nat Methods 6, 55–61 (2009). https://doi.org/10.1038/nmeth.1283

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