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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Synthetic genetic interaction screens in yeast show thousands of combinations of individually viable mutations can be jointly lethal, with similar examples in Drosophila and C. elegans.
“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]
Genes belonging to similar biological processes tend to share common genetic interactions.
“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]
Genetic interaction networks highlight mechanistic connections between genes and their corresponding pathways.
“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]
Synthetic genetic array (SGA) analysis automates the combinatorial construction of defined mutants and enables quantitative analysis of genetic interactions.
“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]
Negative and positive genetic interactions were quantified and false negative/positive rates and data reproducibility were determined at defined confidence thresholds from analysis of biological replicates and comparison of interactions for a subset of gene pairs represented on both mutant arrays.
“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]
Genes encoding proteins that function together within the same pathway or complex display similar genetic interaction profiles.
“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]
Genetic interaction profiles provide a quantitative measurement of functional similarity.
“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]
Similarity networks generated from correlated genetic interaction profiles organize genes into clusters that highlight biological processes.
“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]
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.
“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]
Positive genetic interactions between nonessential genes also overlapped with protein-protein interactions, albeit to a lesser extent (0.5%, 3.7-fold enrichment).
“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]
Essential genes are major hubs and form the basic scaffold of the global genetic interaction network.
“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]
Duplicated genes with overlapping function often are buffered more extensively, such that more complex triple mutant analysis will be required to reveal their genetic interaction profiles.
“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]
Protein complexes exhibited highly organized patterns of genetic interactions.
“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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Cites
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from <i>BRCA</i> Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634 · see citing works
Global landscape of protein complexes in the yeast Saccharomyces cerevisiae
Krogan, N. J., Cagney, G., Yu, H., Zhong, G., Guo, X., Ignatchenko, A., Li, J., Pu, S., Datta, N., Tikuisis, A., et al. (2006) · Nature · doi:10.1038/nature04670 · Cited by 2,915 · see citing works
Self-citationProteome survey reveals modularity of the yeast cell machinery
Gavin, A., Aloy, P., Grandi, P., Krause, R., Böesche, M., Marzioch, M., Rau, C., Jensen, L. J., Bastuck, S., Dümpelfeld, B., et al. (2006) · Nature · doi:10.1038/nature04532 · Cited by 2,544 · see citing works
Waddington, C. H. (2014) · doi:10.4324/9781315765471 · Cited by 2,153 · see citing works
Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants
Tong, A. H. Y., Evangelista, M., Parsons, A. B., Xu, H., Bader, G. D., Pagé, N., Robinson, M., Raghibizadeh, S., Hogue, C. W. V., Bussey, H., et al. (2001) · Science · doi:10.1126/science.1065810 · Cited by 2,138 · see citing works
Self-citationGlobal Mapping of the Yeast Genetic Interaction Network
Tong, A. H. Y., Lesage, G., Bader, G. D., Ding, H., Xu, H., Xin, X., Young, J., Berriz, G. F., Brost, R. L., Chang, M., et al. (2004) · Science · doi:10.1126/science.1091317 · Cited by 2,070 · see citing works
Self-citationHigh-Quality Binary Protein Interaction Map of the Yeast Interactome Network
Yu, H., Braun, P., Yıldırım, M. A., Lemmens, I., Venkatesan, K., Sahalie, J., Hirozane-Kishikawa, T., Gebreab, F., Li, N., Simonis, N., et al. (2008) · Science · doi:10.1126/science.1158684 · Cited by 1,392 · see citing works
Self-citationThe Chemical Genomic Portrait of Yeast: Uncovering a Phenotype for All Genes
Hillenmeyer, M. E., Fung, E., Wildenhain, J., Pierce, S. E., Hoon, S. S., Lee, W., Proctor, M. J., St.Onge, R. P., Tyers, M., Koller, D., et al. (2008) · Science · doi:10.1126/science.1150021 · Cited by 978 · see citing works
Self-citationAn in Vivo Map of the Yeast Protein Interactome
Tarassov, K., Messier, V., Landry, C. R., Radinovic, S., Molina, M. M. S., Shames, I., Malitskaya, Y., Vogel, J., Bussey, H., & Michnick, S. W. (2008) · Science · doi:10.1126/science.1153878 · Cited by 773 · see citing works
Self-citationComprehensive Characterization of Genes Required for Protein Folding in the Endoplasmic Reticulum
Jonikas, M. C., Collins, S. R., Denic, V., Oh, E., Toyama, E. Q., Schmid, V., Weibezahn, J., Schwappach, B., Walter, P., Weissman, J. S., et al. (2009) · Science · doi:10.1126/science.1167983 · Cited by 713 · see citing works
Irvine, R. F., Letcher, A., Heslop, J. P., & Berridge, M. J. (1986) · Nature · doi:10.1038/320631a0 · Cited by 705 · see citing works
PERSPECTIVE: EVOLUTION AND DETECTION OF GENETIC ROBUSTNESS
de Visser, J. A. G. M., Hermisson, J., Wagner, G. P., Ancel, L. W., Bagheri, H. C., Blanchard, J. L., Chao, L., Cheverud, J. M., Elena, S. F., Fontana, W., et al. (2003) · Evolution · doi:10.1111/j.0014-3820.2003.tb00377.x · Cited by 695 · see citing works
Parsons, A. B., Brost, R. L., Ding, H., Li, Z., Zhang, C., Sheikh, B., Brown, G. W., Kane, P. M., Hughes, T. R., & Boone, C. M. (2003) · Nature Biotechnology · doi:10.1038/nbt919 · Cited by 651 · see citing works
Self-citationHighly Expressed Genes in Yeast Evolve Slowly
Pál, C., Papp, B., & Hurst, L. D. (2001) · Genetics · doi:10.1093/genetics/158.2.927 · Cited by 635 · see citing works
Self-citationTumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells
Nebbioso, A., Clarke, N., Voltz, E., Germain, E., Ambrosino, C., Bontempo, P., Álvarez, R., Schiavone, E. M., Ferrara, F., Bresciani, F., et al. (2004) · Nature Medicine · doi:10.1038/nm1161 · Cited by 613 · see citing works
Modular epistasis in yeast metabolism
Segrè, D., DeLuna, A., Church, G. M., & Kishony, R. (2005) · Nature Genetics · doi:10.1038/ng1489 · Cited by 575 · see citing works
Dunham, M. J., Badrane, H., Ferea, T., Adams, J., Brown, P. O., Rosenzweig, F., & Botstein, D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242624799 · Cited by 564 · see citing works
Lehner, B., Crombie, C., Tischler, J., Fortunato, A., & Fraser, A. G. (2006) · Nature Genetics · doi:10.1038/ng1844 · Cited by 502 · see citing works
Relating Three-Dimensional Structures to Protein Networks Provides Evolutionary Insights
Kim, P. M., Lu, L. J., Xia, Y., & Gerstein, M. (2006) · Science · doi:10.1126/science.1136174 · Cited by 473 · see citing works
Self-citationMani, R., St.Onge, R. P., Hartman, J. L., Giaever, G. N., & Roth, F. P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712255105 · Cited by 471 · see citing works
Self-citationPERSPECTIVE:EVOLUTION AND DETECTION OF GENETIC ROBUSTNESS
de Visser, J. A. G. M., Hermisson, J., Wagner, G. P., et al. (2003) · Evolution · doi:10.1554/02-750r · Cited by 364 · see citing works
Huber, A., Bodenmiller, B., Uotila, A., Ståhl, M., Wanka, S., Gerrits, B., Aebersold, R. H., & Loewith, R. (2009) · Genes & Development · doi:10.1101/gad.532109 · Cited by 334 · see citing works
Systematic pathway analysis using high-resolution fitness profiling of combinatorial gene deletions
St.Onge, R. P., Mani, R., Oh, J., Proctor, M. J., Fung, E., Davis, R. W., Nislow, C., Roth, F. P., & Giaever, G. N. (2007) · Nature Genetics · doi:10.1038/ng1948 · Cited by 306 · see citing works
Self-citationSystematic Mapping of Genetic Interaction Networks
Dixon, S. J., Costanzo, M., Baryshnikova, A., Andrews, B., & Boone, C. M. (2008) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.073003.114751 · Cited by 290 · see citing works
Self-citationUbiquitin-related modifier Urm1 acts as a sulphur carrier in thiolation of eukaryotic transfer RNA
Leidel, S. A., Pedrioli, P. G. A., Bucher, T., Brost, R. L., Costanzo, M., Schmidt, A., Aebersold, R. H., Boone, C. M., Hofmann, K., & Peter, M. (2009) · Nature · doi:10.1038/nature07643 · Cited by 282 · see citing works
Self-citationNetwork Hubs Buffer Environmental Variation in Saccharomyces cerevisiae
Levy, S. F., & Siegal, M. L. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060264 · Cited by 279 · see citing works
Esberg, A., Huang, B., Johansson, M., & Byström, A. S. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.07.031 · Cited by 269 · see citing works
Meiklejohn, C. D., & Hartl, D. L. (2002) · Trends in Ecology & Evolution · doi:10.1016/s0169-5347(02)02596-x · Cited by 251 · see citing works
Sevier, C. S., Qu, H., Heldman, N., Gross, E., Fass, D., & Kaiser, C. A. (2007) · Cell · doi:10.1016/j.cell.2007.02.039 · Cited by 242 · see citing works
Self-citationThe role of disorder in interaction networks: a structural analysis
Kim, P. M., Sboner, A., Xia, Y., & Gerstein, M. (2008) · Molecular Systems Biology · doi:10.1038/msb.2008.16 · Cited by 231 · see citing works
Self-citationLehár, J., Stockwell, B. R., Giaever, G., & Nislow, C. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.120 · Cited by 172 · see citing works
Self-citationA simple dependence between protein evolution rate and the number of protein-protein interactions
Fraser, H. B., Wall, D. P., & Hirsh, A. E. (2003) · BMC Evolutionary Biology · doi:10.1186/1471-2148-3-11 · Cited by 171 · see citing works
Rahl, P. B., Chen, C. Z., & Collins, R. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.018 · Cited by 169 · see citing works
LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway
Chen, E. J., & Kaiser, C. A. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200210141 · Cited by 139 · see citing works
Self-citationJohansen, L. D., Naumanen, T., Karnoe, A., Westerlund, N., Gromova, I., Junttila, M. R., Nielsen, C. W., Bøttzauw, T., Tolkovsky, A. M., Westermarck, J. K., et al. (2008) · Journal of Cell Science · doi:10.1242/jcs.013722 · Cited by 104 · see citing works
Hartwell, L. (2004) · Science · doi:10.1126/science.1094731 · Cited by 79 · see citing works
Tough Lessons From Golden Rice
Enserink, M. (2008) · Science · doi:10.1126/science.320.5875.468 · Cited by 69 · see citing works
Metzger, M. B., & Michaelis, S. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-02-0140 · Cited by 63 · see citing works
Naumanen, T., Johansen, L. D., Coffey, E. T., & Kallunki, T. (2008) · Cell Adhesion & Migration · doi:10.4161/cam.2.4.6630 · Cited by 23 · see citing works
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Wang, T., Wei, J. J., Sabatini, D. M., & Lander, E. S. (2014) · Science · doi:10.1126/science.1246981 · Cited by 2,856 · see citing works
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Gilbert, L. A., Horlbeck, M. A., Adamson, B., Villalta, J. E., Chen, Y., Whitehead, E. H., Guimaraes, C., Panning, B., Ploegh, H. L., Bassik, M. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.029 · Cited by 2,728 · see citing works
Self-citationAntibacterial drug discovery in the resistance era
Brown, E. D., & Wright, G. D. (2016) · Nature · doi:10.1038/nature17042 · Cited by 2,265 · see citing works
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Vidal, M., Cusick, M. E., & Barabási, A.-L. (2011) · Cell · doi:10.1016/j.cell.2011.02.016 · Cited by 1,771 · see citing works
High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities.
Hart, T., Chandrashekhar, M., Aregger, M., Steinhart, Z., Brown, K. R., MacLeod, G., Mis, M., Zimmermann, M., Fradet-Turcotte, A., Sun, S., et al. (2015) · Cell · doi:10.1016/j.cell.2015.11.015 · Cited by 1,571 · see citing works
Self-citationRare and common variants: twenty arguments
Gibson, G. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3118 · Cited by 1,278 · see citing works
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Costanzo, M., VanderSluis, B., Koch, E. N., Baryshnikova, A., Pons, C., Tan, G., Wang, W., Usaj, M., Hanchard, J., Lee, S. D., et al. (2016) · Science · doi:10.1126/science.aaf1420 · Cited by 1,240 · see citing works
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Al-Lazikani, B., Banerji, U., & Workman, P. (2012) · Nature Biotechnology · doi:10.1038/nbt.2284 · Cited by 1,070 · see citing works
Horlbeck, M. A., Gilbert, L. A., Villalta, J. E., Adamson, B., Pak, R. A., Chen, Y., Fields, A. P., Park, C. Y., Corn, J. E., Kampmann, M., et al. (2016) · eLife · doi:10.7554/elife.19760 · Cited by 894 · see citing works
Self-citationStructure and dynamics of molecular networks: A novel paradigm of drug discovery
Csermely, P., Korcsmáros, T., Kiss, H., London, G., & Nussinov, R. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.016 · Cited by 889 · see citing works
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Chatr‐aryamontri, A., Breitkreutz, B., Oughtred, R., Boucher, L., Heinicke, S., Chen, D., Stark, C., Breitkreutz, A., Kolas, N. K., O’Donnell, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1204 · Cited by 884 · see citing works
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Taipale, M., Krykbaeva, I., Koeva, M., Kayatekin, C., Westover, K. D., Karras, G. I., & Lindquist, S. (2012) · Cell · doi:10.1016/j.cell.2012.06.047 · Cited by 879 · see citing works
Record, M., Carayon, K., Poirot, M., & Silvente‐Poirot, S. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.10.004 · Cited by 853 · see citing works
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Stark, C., Breitkreutz, B., Chatr‐aryamontri, A., Boucher, L., Oughtred, R., Livstone, M. S., Nixon, J., Auken, K. M. V., Wang, X., Shi, X., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1116 · Cited by 853 · see citing works
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Ideker, T., & Krogan, N. J. (2012) · Molecular Systems Biology · doi:10.1038/msb.2011.99 · Cited by 784 · see citing works
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Demir, E., Cary, M. P., Paley, S., Fukuda, K., Lemer, C., Vastrik, I., Wu, G., D'Eustachio, P., Schaefer, C., Luciano, J., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1666 · Cited by 745 · see citing works
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Self-citationThe Notch signalling system: recent insights into the complexity of a conserved pathway
Guruharsha, K. G., Kankel, M. W., & Artavanis‐Tsakonas, S. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3272 · Cited by 700 · see citing works
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Lee, I., Singh-Blom, U. M., Wang, P. I., Shim, J. E., & Marcotte, E. M. (2011) · Genome Research · doi:10.1101/gr.118992.110 · Cited by 673 · see citing works
Systems genetics approaches to understand complex traits
Civelek, M., & Lusis, A. J. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3575 · Cited by 621 · see citing works
clusterMaker: a multi-algorithm clustering plugin for Cytoscape
Morris, J. H., Apeltsin, L., Newman, A. M., Baumbach, J., Wittkop, T., Su, G., Bader, G. D., & Ferrin, T. E. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-436 · Cited by 609 · see citing works
Self-citationAntifungal Drug Development: Challenges, Unmet Clinical Needs, and New Approaches
Roemer, T., & Krysan, D. J. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019703 · Cited by 593 · see citing works
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Botstein, D., & Fink, G. R. (2011) · Genetics · doi:10.1534/genetics.111.130765 · Cited by 592 · see citing works
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Mitra, K., Carvunis, A.-R., Ramesh, S. K., & Ideker, T. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3552 · Cited by 535 · see citing works
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Tkach, J. M., Yimit, A., Lee, A. Y., Riffle, M. E., Costanzo, M., Jaschob, D., Hendry, J. A., Ou, J., Moffat, J., Boone, C. M., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2549 · Cited by 476 · see citing works
Self-citationHoppins, S. C., Collins, S. R., Cassidy-Stone, A., Hummel, E., DeVay, R. M., Lackner, L. L., Westermann, B., Schuldiner, M., Weissman, J. S., & Nunnari, J. M. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201107053 · Cited by 473 · see citing works
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Novère, N. G. L. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3885 · Cited by 422 · see citing works
MuxViz: a tool for multilayer analysis and visualization of networks
Domenico, M. D., Porter, M. A., & Arenas, A. (2014) · Journal of Complex Networks · doi:10.1093/comnet/cnu038 · Cited by 419 · see citing works
Evolutionary Determinants of Cancer
Greaves, M. F. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0439 · Cited by 411 · see citing works
Genotype to Phenotype: A Complex Problem
Dowell, R. D., Ryan, O. W., Jansen, A., Cheung, D., Agarwala, S. D., Danford, T., Bernstein, D. A., Rolfe, A., Heisler, L. E., Chin, B., et al. (2010) · Science · doi:10.1126/science.1189015 · Cited by 408 · see citing works
Self-citationSystematic exploration of essential yeast gene function with temperature-sensitive mutants
Li, Z., Vizeacoumar, F. J., Bahr, S., Li, J., Warringer, J., Vizeacoumar, F. S., Min, R., VanderSluis, B., Bellay, J., DeVit, M. J., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1832 · Cited by 404 · see citing works
Self-citationExploring genetic interaction manifolds constructed from rich single-cell phenotypes
Norman, T. M., Horlbeck, M. A., Replogle, J. M., Ge, A. Y., Xu, A., Jost, M., Gilbert, L. A., & Weissman, J. S. (2019) · Science · doi:10.1126/science.aax4438 · Cited by 392 · see citing works
Targeting and plasticity of mitochondrial proteins revealed by proximity-specific ribosome profiling
Williams, C. C., Jan, C. H., & Weissman, J. S. (2014) · Science · doi:10.1126/science.1257522 · Cited by 391 · see citing works
Quantitative analysis of fitness and genetic interactions in yeast on a genome scale
Baryshnikova, A., Costanzo, M., Kim, Y., Ding, H., Koh, J., Toufighi, K., Youn, J.-Y., Ou, J., San Luis, B.-J., Bandyopadhyay, S., et al. (2010) · Nature Methods · doi:10.1038/nmeth.1534 · Cited by 364 · see citing works
Self-citationKell, D. B. (2010) · Archives of Toxicology · doi:10.1007/s00204-010-0577-x · Cited by 361 · see citing works
RNA Degradation in Saccharomyces cerevisae
Parker, R. (2012) · Genetics · doi:10.1534/genetics.111.137265 · Cited by 359 · see citing works
MacNeil, L. T., & Walhout, A. J. M. (2011) · Genome Research · doi:10.1101/gr.097378.109 · Cited by 356 · see citing works
Epistasis as the primary factor in molecular evolution
Breen, M. S., Kemena, C., Vlasov, P. K., Notredame, C., & Kondrashov, F. A. (2012) · Nature · doi:10.1038/nature11510 · Cited by 354 · see citing works
Mechanisms and Consequences of Macromolecular Phase Separation
Bergeron-Sandoval, L.-P., Safaee, N., & Michnick, S. W. (2016) · Cell · doi:10.1016/j.cell.2016.05.026 · Cited by 350 · see citing works
Li, X., Zhang, R., Patena, W., Gang, S. S., Blum, S. R., Ivanova, N., Yue, R., Robertson, J. M., Lefebvre, P. A., Fitz‐Gibbon, S. T., et al. (2016) · The Plant Cell · doi:10.1105/tpc.15.00465 · Cited by 347 · see citing works
Passenger deletions generate therapeutic vulnerabilities in cancer
Muller, F. L., Colla, S., Aquilanti, E., Manzo, V. E., Genovese, G., Lee, J., Eisenson, D., Narurkar, R., Deng, P., Nezi, L., et al. (2012) · Nature · doi:10.1038/nature11331 · Cited by 339 · see citing works
Trait Variation in Yeast Is Defined by Population History
Warringer, J., Zörgö, E., Cubillos, F. A., Zia, A., Gjuvsland, A. B., Simpson, J. T., Forsmark, A., Durbin, R. M., Omholt, S. W., Louis, E. J., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002111 · Cited by 338 · see citing works
Network biology concepts in complex disease comorbidities
Hu, J. X., Thomas, C. E., & Brunak, S. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.87 · Cited by 328 · see citing works
Molecular mechanisms of epistasis within and between genes
Lehner, B. (2011) · Trends in Genetics · doi:10.1016/j.tig.2011.05.007 · Cited by 325 · see citing works
Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway
Barlowe, C. K., & Miller, E. A. (2013) · Genetics · doi:10.1534/genetics.112.142810 · Cited by 321 · see citing works
Mapping the Genetic Landscape of Human Cells
Horlbeck, M. A., Xu, A., Wang, M., Bennett, N. K., Park, C. Y., Bogdanoff, D., Adamson, B., Chow, E. D., Kampmann, M., Peterson, T. R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.010 · Cited by 319 · see citing works
Chuang, H., Hofree, M., & Ideker, T. (2010) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100109-104122 · Cited by 316 · see citing works
The evolution of compositionally and functionally distinct actin filaments
Gunning, P. W., Ghoshdastider, U., Whitaker, S., Popp, D., & Robinson, R. C. (2015) · Journal of Cell Science · doi:10.1242/jcs.165563 · Cited by 315 · see citing works
Using networks to measure similarity between genes: association index selection
Bass, J. I. F., Diallo, A., Nelson, J., Soto, J. M., Myers, C. L., & Walhout, A. J. M. (2013) · Nature Methods · doi:10.1038/nmeth.2728 · Cited by 315 · see citing works
Self-citationRubin, A. J., Parker, K. R., Satpathy, A. T., Qi, Y., Wu, B., Ong, A. J., Mumbach, M. R., Ji, A. L., Kim, D. S., Cho, S. W., et al. (2019) · Cell · doi:10.1016/j.cell.2018.11.022 · Cited by 314 · see citing works
Synthetic lethality: General principles, utility and detection using genetic screens in human cells
Nijman, S. M. B. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.11.024 · Cited by 313 · see citing works
History of protein–protein interactions: From egg‐white to complex networks
Falter‐Braun, P., & Gingras, A. (2012) · PROTEOMICS · doi:10.1002/pmic.201100563 · Cited by 308 · see citing works
Self-citationSystematic exploration of synergistic drug pairs
Cokol, M., Chua, H. N., Tasan, M., Mutlu, B., Weinstein, Z., Suzuki, Y., Nergiz, M. E., Costanzo, M., Baryshnikova, A., Giaever, G. N., et al. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.71 · Cited by 308 · see citing works
Self-citationLahiri, S., Chao, J. T., Tavassoli, S., Wong, A. K. O., Choudhary, V., Young, B. P., Loewen, C. J. R., & Prinz, W. A. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001969 · Cited by 306 · see citing works
The expanding scope of DNA sequencing
Shendure, J., & Aiden, E. L. (2012) · Nature Biotechnology · doi:10.1038/nbt.2421 · Cited by 300 · see citing works
Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndromePreprint
Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T., González‐Fernández, Á., Simpson, P. J., D’Santos, C. S., Arends, M. J., et al. (2011) · Genes & Development · doi:10.1101/gad.623011 · Cited by 292 · see citing works
Self-citationMembrane Protein Insertion at the Endoplasmic Reticulum
Shao, S., & Hegde, R. S. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154125 · Cited by 287 · see citing works
Something old, something new: revisiting natural products in antibiotic drug discovery
Wright, G. D. (2014) · Canadian Journal of Microbiology · doi:10.1139/cjm-2014-0063 · Cited by 286 · see citing works
A new era in functional genomics screens
Przybyla, L., & Gilbert, L. A. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00409-w · Cited by 281 · see citing works
Predicting Cancer-Specific Vulnerability via Data-Driven Detection of Synthetic Lethality
Jerby‐Arnon, L., Pfetzer, N., Waldman, Y. Y., McGarry, L., James, D. T., Shanks, E. J., Seashore-Ludlow, B. A., Weinstock, A., Geiger, T., Clemons, P. A., et al. (2014) · Cell · doi:10.1016/j.cell.2014.07.027 · Cited by 279 · see citing works
Microbial laboratory evolution in the era of genome‐scale science
Conrad, T. M., Lewis, N. E., & Palsson, B. Ø. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.42 · Cited by 279 · see citing works
Kemmeren, P., Sameith, K., van de Pasch, L. A. L., Benschop, J. J., Lenstra, T. L., Margaritis, T., O’Duibhir, E., Apweiler, E., van Wageningen, S., Ko, C. W., et al. (2014) · Cell · doi:10.1016/j.cell.2014.02.054 · Cited by 277 · see citing works
Should evolutionary geneticists worry about higher-order epistasis?
Weinreich, D. M., Lan, Y., Wylie, C. S., & Heckendorn, R. B. (2013) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.10.007 · Cited by 277 · see citing works
Machine Learning in Genomic Medicine: A Review of Computational Problems and Data Sets
Leung, M. K. K., Delong, A., Alipanahi, B., & Frey, B. J. (2015) · Proceedings of the IEEE · doi:10.1109/jproc.2015.2494198 · Cited by 276 · see citing works
Methods for biological data integration: perspectives and challenges
Gligorijević, V., & Pržulj, N. (2015) · Journal of The Royal Society Interface · doi:10.1098/rsif.2015.0571 · Cited by 274 · see citing works
Yeast Proteome Dynamics from Single Cell Imaging and Automated Analysis
Chong, Y. T., Koh, J. L. Y., Friesen, H., Kaluarachchi Duffy, S., Cox, M. J., Moses, A., Moffat, J., Boone, C., & Andrews, B. J. (2015) · Cell · doi:10.1016/j.cell.2015.04.051 · Cited by 274 · see citing works
Self-citationThe Regulation of Filamentous Growth in Yeast
Cullen, P. J., & Sprague, G. F. (2012) · Genetics · doi:10.1534/genetics.111.127456 · Cited by 273 · see citing works
A ribosome-associating factor chaperones tail-anchored membrane proteins
Mariappan, M., Li, X., Stefanovic, S., Sharma, A., Mateja, A., Keenan, R. J., & Hegde, R. S. (2010) · Nature · doi:10.1038/nature09296 · Cited by 272 · see citing works
Emerging and evolving concepts in gene essentiality
Rancati, G. I., Moffat, J., Typas, A., & Pavelka, N. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.74 · Cited by 272 · see citing works
Antifungal Drugs: The Current Armamentarium and Development of New Agents
Robbins, N., Wright, G. D., & Cowen, L. E. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.funk-0002-2016 · Cited by 271 · see citing works
Chapter 4: Protein Interactions and Disease
Gonzalez, M. W., & Kann, M. G. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002819 · Cited by 271 · see citing works
Systematic analysis of complex genetic interactions
Kuzmin, E., VanderSluis, B., Wang, W., Tan, G., Deshpande, R., Chen, Y., Ušaj, M., Balint, A., Ušaj, M. M., van Leeuwen, J. S., et al. (2018) · Science · doi:10.1126/science.aao1729 · Cited by 271 · see citing works
Self-citationGladieux, P., Ropars, J., Badouin, H., Branca, A., Aguileta, G., de Vienne, D. M., de la Vega, R. C. R., Branco, S., & Giraud, T. (2013) · Molecular Ecology · doi:10.1111/mec.12631 · Cited by 270 · see citing works
Oliveira, D. L., Nakayasu, E. S., Joffe, L. S., Guimaraes, A. J., Sobreira, T. J. P., Nosanchuk, J. D., Cordero, R. J. B., Frasés, S., Casadevall, A., de Almeida, I. C., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011113 · Cited by 268 · see citing works
Protein-protein interaction networks (PPI) and complex diseases.
Safari‐Alighiarloo, N., Taghizadeh, M., Rezaei–Tavirani, M., Goliaei, B., & Peyvandi, A. A. (2014) · Gastroenterology and hepatology from bed to bench. · Cited by 265 · see citing works
Network link prediction by global silencing of indirect correlations
Barzel, B., & Barabási, A.-Ĺ. (2013) · Nature Biotechnology · doi:10.1038/nbt.2601 · Cited by 262 · see citing works
Impulse Control: Temporal Dynamics in Gene Transcription
Yosef, N., & Regev, A. (2011) · Cell · doi:10.1016/j.cell.2011.02.015 · Cited by 259 · see citing works
Tail-anchored membrane protein insertion into the endoplasmic reticulum
Hegde, R. S., & Keenan, R. J. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3226 · Cited by 258 · see citing works
Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution
Bollenbach, T. (2015) · Current Opinion in Microbiology · doi:10.1016/j.mib.2015.05.008 · Cited by 258 · see citing works
Interaction landscape of membrane-protein complexes in Saccharomyces cerevisiae
Babu, M., Vlasblom, J., Pu, S., Guo, X., Graham, C., Bean, B. D. M., Burston, H. E., Vizeacoumar, F. J., Snider, J. D., Phanse, S., et al. (2012) · Nature · doi:10.1038/nature11354 · Cited by 251 · see citing works
Self-citationThe LC3 interactome at a glance
Wild, P. S., McEwan, D. G., & Đikić, I. (2013) · Journal of Cell Science · doi:10.1242/jcs.140426 · Cited by 250 · see citing works
Henriksen, P., Wagner, S. A., Weinert, B. T., Sharma, S., Bačinskaja, G., Rehman, M., Juffer, A. H., Walther, T. C., Lisby, M., & Choudhary, C. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.017251 · Cited by 246 · see citing works
Miller, K. E., Kim, Y., Huh, W., & Park, H.-O. (2015) · Journal of Molecular Biology · doi:10.1016/j.jmb.2015.03.005 · Cited by 246 · see citing works
Self-citationFrom regions to connections and networks: new bridges between brain and behavior
Mišić, B., & Sporns, O. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.05.003 · Cited by 243 · see citing works
Global Genetic Networks and the Genotype-to-Phenotype Relationship
Costanzo, M., Kuzmin, E., van Leeuwen, J., Mair, B., Moffat, J., Boone, C., & Andrews, B. (2019) · Cell · doi:10.1016/j.cell.2019.01.033 · Cited by 241 · see citing works
Self-citationCompact integration of multi-network topology for functional analysis of genes
Cho, H., Berger, B., & Peng, J. (2016) · Cell Systems · doi:10.1016/j.cels.2016.10.017 · Cited by 241 · see citing works
- 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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