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The Genetic Landscape of a Cell
Open accessAbstract
Making Connections: Genetic interaction profiles highlight cross-connections between bioprocesses, providing a global view of cellular pleiotropy, and enable the prediction of genetic network hubs. Costanzo et al. (p. 425 ) performed a pairwise fitness screen covering approximately one-third of all potential genetic interactions in yeast, examining 5.4 million gene-gene pairs and generating quantitative profiles for ∼75% of the genome. Of the pairwise interactions tested, about 3% of the genes investigated interact under the conditions tested. On the basis of these data, a reference map for the yeast genetic network was created.
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In the citing paper
“Synthetic genetic interaction screens in yeast123,124 have demonstrated that thousands of combinations of individually viable mutations can jointly be lethal, and similar examples have been documented in Drosophila melanogaster and Caenorhabditis elegans125,126.”
From Rare and common variants: twenty arguments (2012) · cites this paper as [124]
In the citing paper
“Genes belonging to similar biological processes tend to share common genetic interactions, and genes encoding proteins that function together within the same pathway or complex display similar genetic interaction profiles (fig. S4)(1).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“Genetic interaction networks highlight mechanistic connections between genes and their corresponding pathways (1).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“Synthetic genetic array (SGA) analysis automates the combinatorial construction of defined mutants and enables the quantitative analysis of genetic interactions (1, 5).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“Negative and positive genetic interactions were quantified and false negative/positive rates and data reproducibility were determined at defined confidence thresholds (1) from analysis of biological replicates and comparison of interactions for a subset of gene pairs represented on both mutant arrays (fig. S2)(8).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“Genes belonging to similar biological processes tend to share common genetic interactions, and genes encoding proteins that function together within the same pathway or complex display similar genetic interaction profiles (fig. S4)(1).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“Thus, genetic interaction profiles provide a quantitative measurement of functional similarity, and similarity networks generated from the large-scale mapping correlated genetic interaction profiles organizes genes into clusters that highlight biological processes (1).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“Thus, genetic interaction profiles provide a quantitative measurement of functional similarity, and similarity networks generated from the large-scale mapping correlated genetic interaction profiles organizes genes into clusters that highlight biological processes (1).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“As observed previously (1), fitness defects associated with both deletion alleles of nonessential genes and TS alleles of essential genes were highly correlated with the degree of genetic interaction (figs. S11–S12; Table S1; Data File S10).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“Consistent with previous observations (1), positive genetic interactions between nonessential genes also overlapped with protein-protein interactions, albeit to a lesser extent (0.5%, 3.7-fold enrichment; Figs. 5C, S15).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“First, consistent with the results of our previous smaller scale surveys (1, 24), essential genes are major hubs and form the basic scaffold of the global genetic interaction network.”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“One interesting case involves duplicated genes with overlapping function, which often are buffered more extensively, such that more complex triple mutant analysis will be required to reveal their genetic interaction profiles (1, 40).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
In the citing paper
“Consistent with previous findings (1, 5, 28, 29), we found that protein complexes exhibited highly organized patterns of genetic interactions.”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [1]
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Metadata
- Authors
- 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., Cokol, M., Deshpande, R., Li, Z., Lin, Z.-Y., Liang, W., Marback, M., Paw, J., San Luis, B.-J., Shuteriqi, E., Tong, A. H. Y., van Dyk, N., Wallace, I. M., Whitney, J. A., Weirauch, M. T., Zhong, G., Zhu, H., Houry, W. A., Brudno, M., Ragibizadeh, S., Papp, B., Pál, C., Roth, F. P., Giaever, G., Nislow, C., Troyanskaya, O. G., Bussey, H., Bader, G. D., Gingras, A.-C., Morris, Q. D., Kim, P. M., Kaiser, C. A., Myers, C. L., Andrews, B. J., & Boone, C.
- Affiliations
- University of Toronto (CA)
- University of Minnesota (US)
- Massachusetts Institute of Technology (US)
- Department of Biochemistry, Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA.
- Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
- Harvard University (US)
- Mount Sinai Hospital (CA)
- University of California, Santa Cruz (US)
- S&P Robotics, Inc., 1181 Finch Avenue West, North York, Ontario M3J 2V8, Canada.
- Institute of Biochemistry (HU)
- Princeton University (US)
- McGill University (CA)
- Corresponding author
- Costanzo, Michael
- Baryshnikova, Anastasia
- Myers, Chad L.
- Andrews, Brenda J.
- Boone, Charles
- ORCID
- Costanzo, Michael
- Baryshnikova, Anastasia
- Spear, Eric D.
- Sevier, Carolyn S.
- Mostafavi, Sara
- VanderSluis, Benjamin
- Vizeacoumar, Franco J.
- Chen, Yiqun
- Cokol, Murat
- Li, Zhijian
- Liang, Wendy
- Tong, Amy Hin Yan
- Wallace, Iain M.
- Weirauch, Matthew T.
- Zhu, Hongwei
- Houry, Walid A.
- Brudno, Michael
- Papp, Balázs
- Pál, Csaba
- Roth, Frederick P.
- Giaever, Guri
- Nislow, Corey
- Troyanskaya, Olga G.
- Bader, Gary D.
- Gingras, Anne-Claude
- Morris, Quaid D.
- Kim, Philip M.
- Myers, Chad L.
- Andrews, Brenda J.
- Boone, Charles
- Venue
- Science
- Published
- 2010-01-22
- Volume
- 327
- Issue
- 5964
- Pages
- 425-431
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5600254
- OpenAlex
- W2133102806
- Cited by
- 2,162
- References
- 38
- Citations by year
- 2026: 36 · 2025: 48 · 2024: 57 · 2023: 70 · 2022: 75 · 2021: 83 · 2020: 93 · 2019: 98 · 2018: 115 · 2017: 159 · 2016: 161 · 2015: 183 · 2014: 203 · 2013: 212 · 2012: 212
- FWCI
- 101.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (084314)
- Canadian Institutes of Health Research (GSP-415-67)
- National Human Genome Research Institute (R01HG003224)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- synthetic genetic interactions, gene-gene interaction, genetic interaction networks, Saccharomyces cerevisiae, gene function annotation, pleiotropy, chemical-genetic interactions, drug target identification
- MeSH terms
- Genes, Fungal, Mutation, Saccharomyces cerevisiae, Gene Expression Regulation, Fungal, Genome, Fungal, Computational Biology, Gene Duplication, Protein Interaction Mapping, Saccharomyces cerevisiae Proteins, Gene Regulatory Networks, Metabolic Networks and Pathways, Genetic Fitness
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