The genetic landscape of a cell

Michael Costanzo; Anastasia Baryshnikova; Jeremy Bellay; Yungil Kim; Eric D. Spear; Carolyn S. Sevier; Huiming Ding; Judice L.Y. Koh; Kiana Toufighi; Sara Mostafavi; Jeany Prinz; Robert P. St. Onge; Benjamin Vandersluis; Taras Makhnevych; Franco J. Vizeacoumar; Solmaz Alizadeh; Sondra Bahr; Renee L. Brost; Yiqun Chen; Murat Cokol; Raamesh Deshpande; Zhijian Li; Zhen Yuan Lin; Wendy Liang; Michaela Marback; Jadine Paw; Bryan Joseph San Luis; Ermira Shuteriqi; Amy Hin Yan Tong; Nydia Van Dyk; Iain M. Wallace; Joseph A. Whitney; Matthew T. Weirauch; Guoqing Zhong; Hongwei Zhu; Walid A. Houry; Michael Brudno; Sasan Ragibizadeh; Balázs Papp; Csaba Pál; Frederick P. Roth; Guri Giaever; Corey Nislow; Olga G. Troyanskaya; Howard Bussey; Gary D. Bader; Anne Claude Gingras; Quaid D. Morris; Philip M. Kim; Chris A. Kaiser; Chad L. Myers; Brenda J. Andrews; Charles Boone

doi:10.1126/science.1180823

The genetic landscape of a cell

Michael Costanzo, Anastasia Baryshnikova, Jeremy Bellay, Yungil Kim, Eric D. Spear, Carolyn S. Sevier, Huiming Ding, Judice L.Y. Koh, Kiana Toufighi, Sara Mostafavi, Jeany Prinz, Robert P. St. Onge, Benjamin Vandersluis, Taras Makhnevych, Franco J. Vizeacoumar, Solmaz Alizadeh, Sondra Bahr, Renee L. Brost, Yiqun Chen, Murat CokolRaamesh Deshpande, Zhijian Li, Zhen Yuan Lin, Wendy Liang, Michaela Marback, Jadine Paw, Bryan Joseph San Luis, Ermira Shuteriqi, Amy Hin Yan Tong, Nydia Van Dyk, Iain M. Wallace, Joseph A. Whitney, Matthew T. Weirauch, Guoqing Zhong, Hongwei Zhu, Walid A. Houry, Michael Brudno, Sasan Ragibizadeh, Balázs Papp, Csaba Pál, Frederick P. Roth, Guri Giaever, Corey Nislow, Olga G. Troyanskaya, Howard Bussey, Gary D. Bader, Anne Claude Gingras, Quaid D. Morris, Philip M. Kim, Chris A. Kaiser, Chad L. Myers, Brenda J. Andrews, Charles Boone

Research output: Contribution to journal › Article › peer-review

1513 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	425-431
Number of pages	7
Journal	Science
Volume	327
Issue number	5964
DOIs	https://doi.org/10.1126/science.1180823
State	Published - Jan 22 2010
Externally published	Yes

ASJC Scopus subject areas

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10.1126/science.1180823

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Costanzo, M., Baryshnikova, A., Bellay, J., Kim, Y., Spear, E. D., Sevier, C. S., Ding, H., Koh, J. L. Y., Toufighi, K., Mostafavi, S., Prinz, J., St. Onge, R. P., Vandersluis, B., Makhnevych, T., Vizeacoumar, F. J., Alizadeh, S., Bahr, S., Brost, R. L., Chen, Y., ... Boone, C. (2010). The genetic landscape of a cell. Science, 327(5964), 425-431. https://doi.org/10.1126/science.1180823

Costanzo, M, Baryshnikova, A, Bellay, J, Kim, Y, Spear, ED, Sevier, CS, Ding, H, Koh, JLY, Toufighi, K, Mostafavi, S, Prinz, J, St. Onge, RP, Vandersluis, B, Makhnevych, T, Vizeacoumar, FJ, Alizadeh, S, Bahr, S, Brost, RL, Chen, Y, Cokol, M, Deshpande, R, Li, Z, Lin, ZY, Liang, W, Marback, M, Paw, J, Luis, BJS, Shuteriqi, E, Tong, AHY, Van Dyk, N, Wallace, IM, Whitney, JA, Weirauch, MT, Zhong, G, Zhu, H, Houry, WA, Brudno, M, Ragibizadeh, S, Papp, B, Pál, C, Roth, FP, Giaever, G, Nislow, C, Troyanskaya, OG, Bussey, H, Bader, GD, Gingras, AC, Morris, QD, Kim, PM, Kaiser, CA, Myers, CL, Andrews, BJ & Boone, C 2010, 'The genetic landscape of a cell', Science, vol. 327, no. 5964, pp. 425-431. https://doi.org/10.1126/science.1180823

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title = "The genetic landscape of a cell",

abstract = "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.",

author = "Michael Costanzo and Anastasia Baryshnikova and Jeremy Bellay and Yungil Kim and Spear, {Eric D.} and Sevier, {Carolyn S.} and Huiming Ding and Koh, {Judice L.Y.} and Kiana Toufighi and Sara Mostafavi and Jeany Prinz and {St. Onge}, {Robert P.} and Benjamin Vandersluis and Taras Makhnevych and Vizeacoumar, {Franco J.} and Solmaz Alizadeh and Sondra Bahr and Brost, {Renee L.} and Yiqun Chen and Murat Cokol and Raamesh Deshpande and Zhijian Li and Lin, {Zhen Yuan} and Wendy Liang and Michaela Marback and Jadine Paw and Luis, {Bryan Joseph San} and Ermira Shuteriqi and Tong, {Amy Hin Yan} and {Van Dyk}, Nydia and Wallace, {Iain M.} and Whitney, {Joseph A.} and Weirauch, {Matthew T.} and Guoqing Zhong and Hongwei Zhu and Houry, {Walid A.} and Michael Brudno and Sasan Ragibizadeh and Bal{\'a}zs Papp and Csaba P{\'a}l and Roth, {Frederick P.} and Guri Giaever and Corey Nislow and Troyanskaya, {Olga G.} and Howard Bussey and Bader, {Gary D.} and Gingras, {Anne Claude} and Morris, {Quaid D.} and Kim, {Philip M.} and Kaiser, {Chris A.} and Myers, {Chad L.} and Andrews, {Brenda J.} and Charles Boone",

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doi = "10.1126/science.1180823",

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T1 - The genetic landscape of a cell

AU - Costanzo, Michael

AU - Baryshnikova, Anastasia

AU - Bellay, Jeremy

AU - Kim, Yungil

AU - Spear, Eric D.

AU - Sevier, Carolyn S.

AU - Ding, Huiming

AU - Koh, Judice L.Y.

AU - Toufighi, Kiana

AU - Mostafavi, Sara

AU - Prinz, Jeany

AU - St. Onge, Robert P.

AU - Vandersluis, Benjamin

AU - Makhnevych, Taras

AU - Vizeacoumar, Franco J.

AU - Alizadeh, Solmaz

AU - Bahr, Sondra

AU - Brost, Renee L.

AU - Chen, Yiqun

AU - Cokol, Murat

AU - Deshpande, Raamesh

AU - Li, Zhijian

AU - Lin, Zhen Yuan

AU - Liang, Wendy

AU - Marback, Michaela

AU - Paw, Jadine

AU - Luis, Bryan Joseph San

AU - Shuteriqi, Ermira

AU - Tong, Amy Hin Yan

AU - Van Dyk, Nydia

AU - Wallace, Iain M.

AU - Whitney, Joseph A.

AU - Weirauch, Matthew T.

AU - Zhong, Guoqing

AU - Zhu, Hongwei

AU - Houry, Walid A.

AU - Brudno, Michael

AU - Ragibizadeh, Sasan

AU - Papp, Balázs

AU - Pál, Csaba

AU - Roth, Frederick P.

AU - Giaever, Guri

AU - Nislow, Corey

AU - Troyanskaya, Olga G.

AU - Bussey, Howard

AU - Bader, Gary D.

AU - Gingras, Anne Claude

AU - Morris, Quaid D.

AU - Kim, Philip M.

AU - Kaiser, Chris A.

AU - Myers, Chad L.

AU - Andrews, Brenda J.

AU - Boone, Charles

PY - 2010/1/22

Y1 - 2010/1/22

N2 - 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.

AB - 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.

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DO - 10.1126/science.1180823

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SN - 0036-8075

VL - 327

SP - 425

EP - 431

JO - Science

JF - Science

IS - 5964

ER -

The genetic landscape of a cell

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