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The Plasmodium protein network diverges from those of other eukaryotes


Plasmodium falciparum is the pathogen responsible for over 90% of human deaths from malaria1. Therefore, it has been the focus of a considerable research initiative, involving the complete DNA sequencing of the genome2, large-scale expression analyses3,4, and protein characterization of its life-cycle stages5. The Plasmodium genome sequence is relatively distant from those of most other eukaryotes, with more than 60% of the 5,334 encoded proteins lacking any notable sequence similarity to other organisms2. To systematically elucidate functional relationships among these proteins, a large two-hybrid study has recently mapped a network of 2,846 interactions involving 1,312 proteins within Plasmodium6. This network adds to a growing collection of available interaction maps for a number of different organisms, and raises questions about whether the divergence of Plasmodium at the sequence level is reflected in the configuration of its protein network. Here we examine the degree of conservation between the Plasmodium protein network and those of model organisms. Although we find 29 highly connected protein complexes specific to the network of the pathogen, we find very little conservation with complexes observed in other organisms (three in yeast, none in the others). Overall, the patterns of protein interaction in Plasmodium, like its genome sequence, set it apart from other species.

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Figure 1: Conserved and distinct complexes within P. falciparum.
Figure 2: Network similarity across the five organisms.
Figure 3: Number of interactions per protein and the signal-to-noise ratio of protein complexes.
Figure 4: Functional roles within the Plasmodium protein network.

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We are indebted to M. Vignali, D. LaCount and S. Fields at the University of Washington, and B. Hughes and S. Sahasrabudhe at Prolexys, for providing us with advance access to the Plasmodium interaction data and for suggestions on our manuscript. We also thank E. Winzeler and J. Vinetz for advice on Plasmodium protein function, R. Sharan for help with the PathBLAST algorithm, and V. Bafna for assistance with the false-positive analysis. Finally, we acknowledge the following funding support: the National Science Foundation (S.S.); the National Institute of General Medical Sciences (T.I.); a David and Lucille Packard Fellowship award (T.I.); the Howard Hughes Medical Institute (T.S.); and Unilever (T.S.). Author Contributions S.S. and T.S. contributed equally to this work. All authors discussed the results and wrote the paper.

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Correspondence to Silpa Suthram.

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This file contains the Supplementary Methods, Supplementary Figures 1–3 and Supplementary Tables 1–7. (DOC 1636 kb)

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Suthram, S., Sittler, T. & Ideker, T. The Plasmodium protein network diverges from those of other eukaryotes. Nature 438, 108–112 (2005).

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