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Effect of sampling on topology predictions of protein-protein interaction networks

Nature Biotechnology volume 23, pages 839–844 (2005)Cite this article

Abstract

Currently available protein-protein interaction (PPI) network or 'interactome' maps, obtained with the yeast two-hybrid (Y2H) assay or by co-affinity purification followed by mass spectrometry (co-AP/MS), only cover a fraction of the complete PPI networks. These partial networks display scale-free topologies–most proteins participate in only a few interactions whereas a few proteins have many interaction partners. Here we analyze whether the scale-free topologies of the partial networks obtained from Y2H assays can be used to accurately infer the topology of complete interactomes. We generated four theoretical interaction networks of different topologies (random, exponential, power law, truncated normal). Partial sampling of these networks resulted in sub-networks with topological characteristics that were virtually indistinguishable from those of currently available Y2H-derived partial interactome maps. We conclude that given the current limited coverage levels, the observed scale-free topology of existing interactome maps cannot be confidently extrapolated to complete interactomes.

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Figure 1: Sampling of an Erdös-Rényi random network.
Figure 2: Sampled networks derived from starting networks of various topologies.
Figure 3: Degree distribution of sampled networks.

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Acknowledgements

We thank Mike Boxem, Fritz Roth and Debra Goldberg for extremely useful discussions and careful reading of the manuscript. This work was supported by grants from NIGMS, NHGRI, and NCI to M.V.

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Author notes

  1. Jing-Dong J Han

    Present address: Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Datun Road, Beijing, 100101, China

  2. Jing-Dong J Han and Denis Dupuy: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Cancer Systems Biology and Department of Cancer Biology, and Department of Genetics, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, 02115, Massachusetts, USA

    Jing-Dong J Han, Denis Dupuy, Nicolas Bertin, Michael E Cusick & Marc Vidal

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  1. Jing-Dong J Han
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Correspondence to Marc Vidal.

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Supplementary information

Supplementary Fig. 1

Degree distribution of the complete theoretical networks. (PDF 851 kb)

Supplementary Fig. 2

Sampled networks derived from starting networks of various topologies. (PDF 4952 kb)

Supplementary Fig. 3

Degree distribution of sampled networks. (PDF 4683 kb)

Supplementary Table 1

Comparison between the PPI maps and sampled networks of similar size. (XLS 21 kb)

Supplementary Note (PDF 98 kb)

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Han, JD., Dupuy, D., Bertin, N. et al. Effect of sampling on topology predictions of protein-protein interaction networks. Nat Biotechnol 23, 839–844 (2005). https://doi.org/10.1038/nbt1116

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