Protein interaction mapping: A Drosophila case study

  1. Etienne Formstecher1,
  2. Sandra Aresta1,
  3. Vincent Collura1,
  4. Alexandre Hamburger1,
  5. Alain Meil1,
  6. Alexandra Trehin2,
  7. Céline Reverdy1,
  8. Virginie Betin2,
  9. Sophie Maire2,
  10. Christine Brun9,
  11. Bernard Jacq9,
  12. Monique Arpin3,
  13. Yohanns Bellaiche3,
  14. Saverio Bellusci3,
  15. Philippe Benaroch4,
  16. Michel Bornens3,
  17. Roland Chanet10,
  18. Philippe Chavrier3,
  19. Olivier Delattre5,
  20. Valérie Doye3,
  21. Richard Fehon11,21,
  22. Gérard Faye10,
  23. Thierry Galli12,
  24. Jean-Antoine Girault12,
  25. Bruno Goud3,
  26. Jean de Gunzburg6,
  27. Ludger Johannes3,
  28. Marie-Pierre Junier13,
  29. Vincent Mirouse14,
  30. Ashim Mukherjee15,
  31. Dora Papadopoulo7,
  32. Franck Perez3,
  33. Anne Plessis16,
  34. Carine Rossé6,
  35. Simon Saule10,
  36. Dominique Stoppa-Lyonnet8,
  37. Alain Vincent17,
  38. Michael White18,
  39. Pierre Legrain1,20,
  40. Jérôme Wojcik1,19,
  41. Jacques Camonis2,6,19,22, and
  42. Laurent Daviet1,19,22
  1. 1 Hybrigenics, 75014 Paris, France
  2. 2 The Institut Curie/Hybrigenics Laboratory, Institut Curie, 75248 Paris, France
  3. 3 CNRS UMR 144, Institut Curie, 75248 Paris, France
  4. 4 Inserm U520, Institut Curie, 75248 Paris, France
  5. 5 Inserm U509, Institut Curie, 75248 Paris, France
  6. 6 Inserm U528, Institut Curie, 75248 Paris, France
  7. 7 CNRS UMR 218, Institut Curie, 75248 Paris, France
  8. 8 Section Médicale/Service de Génétique, Institut Curie, 75248 Paris, France
  9. 9 LGPD-IBDM, 13288 Marseille, France
  10. 10 CNRS UMR 146, Institut Curie, 91405 Orsay, France
  11. 11 Department of Biology, Duke University, Durham, North Carolina 27708-1000, USA
  12. 12 Inserm U536, Institut du Fer à Moulin, 75005 Paris, France
  13. 13 Inserm U114, Collège de France, 75231 Paris, France
  14. 14 Inserm UMR 384, 63 001 Clermont-Ferrand, France
  15. 15 Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA
  16. 16 CNRS UMR 7592, Institut Jacques Monod, 75251 Paris, France
  17. 17 CNRS UMR 5547 Université Paul Sabatier, 31062 Toulouse, France
  18. 18 Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas 75390-9039, USA

Abstract

The Drosophila (fruit fly) model system has been instrumental in our current understanding of human biology, development, and diseases. Here, we used a high-throughput yeast two-hybrid (Y2H)-based technology to screen 102 bait proteins from Drosophila melanogaster, most of them orthologous to human cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. More than 2300 protein-protein interactions (PPI) were identified, of which 710 are of high confidence. The computation of a reliability score for each protein-protein interaction and the systematic identification of the interacting domain combined with a prediction of structural/functional motifs allow the elaboration of known complexes and the identification of new ones. The full data set can be visualized using a graphical Web interface, the PIMRider (http://pim.hybrigenics.com), and is also accessible in the PSI standard Molecular Interaction data format. Our fly Protein Interaction Map (PIM) is surprisingly different from the one recently proposed by Giot et al. with little overlap between the two data sets. Analysis of the differences in data sets and methods suggests alternative strategies to enhance the accuracy and comprehensiveness of the post-genomic generation of broad-scale protein interaction maps.

Footnotes

  • [Supplemental material is available online at www.genome.org. The interaction data described in this study have been submitted to FlyBase, BIND (accession numbers: 146576-146804 and 146805-148829 for the Drosophila head and embryo interactions, respectively), and the IMEX (International Molecular Interaction Exchange) consortium (accession numbers: IMEX0000001 and IMEX0000002 for the Drosophila embryo and head interactions, respectively). The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: M. Rosbash and P. Maroy.]

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.2659105. Article published online ahead of print in February 2004.

  • ↵21 Present address: Department of Molecular Genetics and Cell Biology, Univ. of Chicago, Chicago, IL 60637, USA.

  • ↵20 Present address: Département de Biologie, CEA-Saclay, 91191, Gifsur-Yvette, France.

  • ↵19 These authors contributed equally to this work.

  • ↵22 Corresponding authors. E-mail jcamonis{at}curie.fr; fax 33 (0)142346650. E-mail ldaviet{at}hybrigenics.fr; fax 33 (0)158103849.

    • Accepted January 6, 2005.
    • Received April 7, 2004.
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  1. Published in Advance February 14, 2005, doi: 10.1101/gr.2659105 Genome Res. 15: 376-384 Cold Spring Harbor Laboratory Press

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