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Protein interaction maps for complete genomes based on gene fusion events

Nature volume 402, pages 86–90 (1999)Cite this article

Abstract

A large-scale effort to measure, detect and analyse protein–protein interactions using experimental methods is under way1,2. These include biochemistry such as co-immunoprecipitation or crosslinking, molecular biology such as the two-hybrid system or phage display, and genetics such as unlinked noncomplementing mutant detection3. Using the two-hybrid system4, an international effort to analyse the complete yeast genome is in progress5. Evidently, all these approaches are tedious, labour intensive and inaccurate6. From a computational perspective, the question is how can we predict that two proteins interact from structure or sequence alone. Here we present a method that identifies gene-fusion events in complete genomes, solely based on sequence comparison. Because there must be selective pressure for certain genes to be fused over the course of evolution, we are able to predict functional associations of proteins. We show that 215 genes or proteins in the complete genomes of Escherichia coli, Haemophilus influenzae and Methanococcus jannaschii are involved in 64 unique fusion events. The approach is general, and can be applied even to genes of unknown function.

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Figure 1: Flowchart of the algorithm.
Figure 2: Representation of protein interaction maps for the most likely interactions predicted for E. coli, H. influenzae and M. jannaschii.
Figure 3: The dependence of the number of true and false positive hits with respect to the Z-score threshold used.

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Acknowledgements

We thank M. Carroll and S. Searle for technical advice. This work was supported by the European Molecular Biology Laboratory and the TMR Programme of the European Commission DGXII (Science, Research and Development). Patent application filed on behalf of the European Molecular Biology Laboratory.

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Author notes

  1. Christos A. Ouzounis: Correspondence and requests for materials should be addressed to C.A.O

Authors and Affiliations

  1. Computational Genomics Group, Research Programme, The European Bioinformatics Institute, EMBL Cambridge Outstation, Cambridge, CB10 1SD, UK

    Anton J. Enright, Ioannis Iliopoulos, Nikos C. Kyrpides & Christos A. Ouzounis

  2. Integrated Genomics Inc., 2201 West Campbell Park Drive, Chicago, 60612, Illinois, USA

    Nikos C. Kyrpides

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  1. Anton J. Enright
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  2. Ioannis Iliopoulos
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  4. Christos A. Ouzounis
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Correspondence to Christos A. Ouzounis.

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Enright, A., Iliopoulos, I., Kyrpides, N. et al. Protein interaction maps for complete genomes based on gene fusion events. Nature 402, 86–90 (1999). https://doi.org/10.1038/47056

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