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The Genetic Landscape of a Cell

Science, 22 January 2010
Vol. 327, Issue 5964, p. 425-431
DOI: 10.1126/science.1180823

The Genetic Landscape of a Cell

  1. Michael Costanzo1,2,*,
  2. Anastasia Baryshnikova1,2,*,
  3. Jeremy Bellay3,
  4. Yungil Kim3,
  5. Eric D. Spear4,
  6. Carolyn S. Sevier4,
  7. Huiming Ding1,2,
  8. Judice L.Y. Koh1,2,
  9. Kiana Toufighi1,2,
  10. Sara Mostafavi1,5,
  11. Jeany Prinz1,2,
  12. Robert P. St. Onge6,
  13. Benjamin VanderSluis3,
  14. Taras Makhnevych7,
  15. Franco J. Vizeacoumar1,2,
  16. Solmaz Alizadeh1,2,
  17. Sondra Bahr1,2,
  18. Renee L. Brost1,2,
  19. Yiqun Chen1,2,
  20. Murat Cokol8,
  21. Raamesh Deshpande3,
  22. Zhijian Li1,2,
  23. Zhen-Yuan Lin9,
  24. Wendy Liang1,2,
  25. Michaela Marback1,2,
  26. Jadine Paw1,2,
  27. Bryan-Joseph San Luis1,2,
  28. Ermira Shuteriqi1,2,
  29. Amy Hin Yan Tong1,2,
  30. Nydia van Dyk1,2,
  31. Iain M. Wallace1,2,10,
  32. Joseph A. Whitney1,5,
  33. Matthew T. Weirauch11,
  34. Guoqing Zhong1,2,
  35. Hongwei Zhu1,2,
  36. Walid A. Houry7,
  37. Michael Brudno1,5,
  38. Sasan Ragibizadeh12,
  39. Balázs Papp13,
  40. Csaba Pál13,
  41. Frederick P. Roth8,
  42. Guri Giaever2,10,
  43. Corey Nislow1,2,
  44. Olga G. Troyanskaya14,
  45. Howard Bussey15,
  46. Gary D. Bader1,2,
  47. Anne-Claude Gingras9,
  48. Quaid D. Morris1,2,5,
  49. Philip M. Kim1,2,
  50. Chris A. Kaiser4,
  51. Chad L. Myers3,,
  52. Brenda J. Andrews1,2,,
  53. Charles Boone1,2,
  1. 1Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  2. 2Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  3. 3Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
  4. 4Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  5. 5Department of Computer Science, University of Toronto, Toronto, Ontario M5S 2E4, Canada.
  6. 6Department of Biochemistry, Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA.
  7. 7Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
  8. 8Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  9. 9Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
  10. 10Department of Pharmacy, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  11. 11Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA.
  12. 12S&P Robotics, Inc., 1181 Finch Avenue West, North York, Ontario M3J 2V8, Canada.
  13. 13Institute of Biochemistry, Biological Research Center, H-6701 Szeged, Hungary.
  14. 14Department of Computer Science, Lewis-Sigler Institute for Integrative Genomics, Carl Icahn Laboratory, Princeton University, Princeton, NJ 08544, USA.
  15. 15Biology Department, McGill University, Montreal, Quebec H3A 1B1, Canada.
  1. To whom correspondence should be addressed. E-mail: cmyers{at} (C.L.M.); brenda.andrews{at} (B.J.A.); charlie.boone{at} (C.B.)


A genome-scale genetic interaction map was constructed by examining 5.4 million gene-gene pairs for synthetic genetic interactions, generating quantitative genetic interaction profiles for ~75% of all genes in the budding yeast, Saccharomyces cerevisiae. A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function. The global network identifies functional cross-connections between all bioprocesses, mapping a cellular wiring diagram of pleiotropy. Genetic interaction degree correlated with a number of different gene attributes, which may be informative about genetic network hubs in other organisms. We also demonstrate that extensive and unbiased mapping of the genetic landscape provides a key for interpretation of chemical-genetic interactions and drug target identification.

  • * These authors contributed equally to this work.

  • Received for publication 20 August 2009.
  • Accepted for publication 12 November 2009.


M. Costanzo, A. Baryshnikova, J. Bellay, Y. Kim, E. D. Spear, C. S. Sevier, H. Ding, J. L. Koh, K. Toufighi, S. Mostafavi, J. Prinz, R. P. St. Onge, B. VanderSluis, T. Makhnevych, F. J. Vizeacoumar, S. Alizadeh, S. Bahr, R. L. Brost, Y. Chen, M. Cokol, R. Deshpande, Z. Li, Z.-Y. Lin, W. Liang, M. Marback, J. Paw, B.-J. San Luis, E. Shuteriqi, A. H. Tong, N. van Dyk, I. M. Wallace, J. A. Whitney, M. T. Weirauch, G. Zhong, H. Zhu, W. A. Houry, M. Brudno, S. Ragibizadeh, B. Papp, C. Pál, F. P. Roth, G. Giaever, C. Nislow, O. G. Troyanskaya, H. Bussey, G. D. Bader, A.-C. Gingras, Q. D. Morris, P. M. Kim, C. A. Kaiser, C. L. Myers, B. J. Andrews, and C. Boone, The Genetic Landscape of a Cell. Science 327, 425-431 (2010).

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