The Concept of Synthetic Lethality in the Context of Anticancer Therapy (original) (raw)

• Kaelin, W. G. Jr. Choosing anticancer drug targets in the postgenomic era. J. Clin. Invest. 104, 1503–1506 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Reddy, A. & Kaelin, W. G. Jr. Using cancer genetics to guide the selection of anticancer drug targets. Curr. Opin. Pharmacol. 2, 366–373 (2002).
  Article CAS PubMed Google Scholar
• Kaelin, W. G. Jr. Gleevec: prototype or outlier? Sci. STKE 2004, PE12 (2004). References 1–3 provide counter-arguments to naysayers who suggest that genetically complex cancers will never be successfully treated with drugs.
• Hartman, J. T., Garvik, B. & Hartwell, L. Principles for the buffering of genetic variation. Science 291, 1001–1004 (2001).
  Article CAS PubMed Google Scholar
• Guarente, L. Synthetic enhancement in gene interaction: a genetic tool come of age. Trends Genet. 9, 362–366 (1993).
  Article CAS PubMed Google Scholar
• Kamb, A. Mutation load, functional overlap, and synthetic lethality in the evolution and treatment of cancer. J. Theor. Biol. 223, 205–213 (2003). This paper and reference 58 are thoughtful essays on maladaptive genetic changes in cancer cells that might render them vunerable to pharmacological attack.
  Article CAS PubMed Google Scholar
• Friend, S. & Oliff, A. Emerging uses for genomic information in drug discovery. N. Engl. J. Med. 338, 125–126 (1998).
  Article CAS PubMed Google Scholar
• Dobzhansky, T. Genetics of natural populations. XIII. Recombination and variability in populations of Drosophila pseudoobscura. Genetics 31, 269–290 (1946).
  Article CAS PubMed PubMed Central Google Scholar
• Lucchesi, J. C. Synthetic lethality and semi-lethality among functionally related mutants of Drosophila melanogaster. Genetics 59, 37–44 (1968).
  Article CAS PubMed PubMed Central Google Scholar
• Sharom, J. R., Bellows, D. S. & Tyers, M. From large networks to small molecules. Curr. Opin. Chem. Biol. 8, 81–90 (2004). Excellent introduction to systems biology as applied to cancer and cancer pharmacology.
  Article CAS PubMed Google Scholar
• Kroll, E. S., Hyland, K. M., Hieter, P. & Li, J. J. Establishing genetic interactions by a synthetic dosage lethality phenotype. Genetics 143, 95–102 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Measday, V. & Hieter, P. Synthetic dosage lethality. Methods Enzymol. 350, 316–326 (2002).
  Article CAS PubMed Google Scholar
• Li, J. J. & Herskowitz, I. Isolation of ORC6, a component of the yeast origin recognition complex by a one-hybrid system. Science 262, 1870–1874 (1993).
  Article CAS PubMed Google Scholar
• Tong, A. H. et al. Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science 294, 2364–2368 (2001).
  Article CAS PubMed Google Scholar
• Tong, A. H. et al. Global mapping of the yeast genetic interaction network. Science 303, 808–813 (2004). References 14 and 15 provide a glimpse into the complexity of synthetic lethal networks in yeast.
  Article CAS PubMed Google Scholar
• Hartwell, L., Szankasi, P., Roberts, C., Murray, A. & Friend, S. Integrating genetic approaches into the discovery of anticancer drugs. Science 278, 1064–1068 (1997). This seminal paper argues that synthetic lethal interactions be exploited to arrive at safer, more efficacious cancer drugs.
  Article CAS PubMed Google Scholar
• Sellers, W. R. & Kaelin, W. G. Jr. Role of the retinoblastoma protein in the pathogenesis of human cancer. J. Clin. Oncol. 15, 3301–3312 (1997).
  Article CAS PubMed Google Scholar
• Nip, J. et al. E2F-1 cooperates with topoisomerase II inhibition and DNA damage to selectively augment p53-independent apoptosis. Mol. Cell. Biol. 17, 1049–1056 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Almasan, A. et al. Deficiency of retinoblastoma protein leads to inappropriate S-phase entry, activation of E2F-responsive genes, and apoptosis. Proc. Natl Acad. Sci. USA 92, 5436–5440 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Banerjee, D. et al. Role of E2F-1 in chemosensitivity. Cancer Res. 58, 4292–4296 (1998).
  CAS PubMed Google Scholar
• Dolma, S., Lessnick, S. L., Hahn, W. C. & Stockwell, B. R. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3, 285–296 (2003).
  Article CAS PubMed Google Scholar
• Evan, G. I. & Vousden, K. H. Proliferation, cell cycle and apoptosis in cancer. Nature 411, 342–348 (2001).
  Article CAS PubMed Google Scholar
• Zaika, A., Irwin, M., Sansome, C. & Moll, U. M. Oncogenes induce and activate endogenous p73 protein. J. Biol. Chem. 276, 11310–11316 (2001).
  Article CAS PubMed Google Scholar
• Meng, R., Phillips, P. & El-Deiry, W. p53-independent increase in E2F-1 expression enhances the cytoxic effects of etoposide and of adriamycin. Intl J. Oncol. 14, 5–14 (1999).
  CAS Google Scholar
• Irwin, M. S. et al. Chemosensitivity linked to p73 function. Cancer Cell 3, 403–410 (2003).
  Article CAS PubMed Google Scholar
• Rutherford, S. L. & Lindquist, S. HSP90 as a capacitor for morphological evolution. Nature 396, 336–342 (1998).
  Article CAS PubMed Google Scholar
• Isaacs, J. S., Xu, W. & Neckers, L. Heat shock protein 90 as a molecular target for cancer therapeutics. Cancer Cell 3, 213–217 (2003).
  Article CAS PubMed Google Scholar
• Workman, P. Altered states: selectively drugging the HSP90 cancer chaperone. Trends Mol. Med. 10, 47–51 (2004).
  Article CAS PubMed Google Scholar
• Neckers, L. & Neckers, K. Heat-shock protein 90 inhibitors as novel cancer chemotherapeutics – an update. Expert Opin. Emerg. Drugs 10, 137–149 (2005).
  Article CAS PubMed Google Scholar
• Goldberg, A. L. Protein degradation and protection against misfolded or damaged proteins. Nature 426, 895–899 (2003).
  Article CAS PubMed Google Scholar
• Rajkumar, S. V., Richardson, P. G., Hideshima, T. & Anderson, K. C. Proteasome inhibition as a novel therapeutic target in human cancer. J. Clin. Oncol. 23, 630–639 (2005).
  Article CAS PubMed Google Scholar
• Krek, W., Xu, G., & Livingston, D. M. Cyclin A-kinase regulation of E2F1 DNA binding function underlies suppression of an S phase checkpoint. Cell 83, 1149–1158 (1995).
  Article CAS PubMed Google Scholar
• Dynlacht, B. D., Flores, O., Lees, J. A. & Harlow, E. Differential regulation of E2F transactivation by cyclin/CDK complexes. Genes Dev. 8, 1772–1786 (1994).
  Article CAS PubMed Google Scholar
• Krek, W. et al. Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinase. Cell 78, 161–172 (1994).
  Article CAS PubMed Google Scholar
• Xu, M., Sheppard, K. A., Peng, C-Y., Yee, A. S. & Piwnica-Worms, H. Cyclin A/CDK2 binds directly to E2F1 and inhibits the DNA-binding activity of E2F1/DP1 by phosphorylation. Mol. Cell. Biol. 14, 8420–8431 (1994).
  CAS PubMed PubMed Central Google Scholar
• Parr, M. J. et al. Tumor-selective transgene expression in vivo mediated by an E2F-responsive adenoviral vector. Nature Med. 3, 1145–1149 (1997).
  Article CAS PubMed Google Scholar
• Chen, Y. et al. Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists. Proc. Natl Acad. Sci. USA 96, 4325–4329 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Chen, W., Lee, J., Cho, S. Y. & Fine, H. A. Proteasome-mediated destruction of the cyclin A/cyclin-dependent kinase 2 complex suppresses tumor cell growth in vitro and in vivo. Cancer Res. 64, 3949–3957 (2004).
  Article CAS PubMed Google Scholar
• Mendoza, N. et al. Selective cyclin-dependent kinase 2/cyclin A antagonists that differ from ATP site inhibitors block tumor growth. Cancer Res. 63, 1020–1024 (2003).
  CAS PubMed Google Scholar
• Tetsu, O. & McCormick, F. Proliferation of cancer cells despite CDK2 inhibition. Cancer Cell 3, 233–245 (2003).
  Article CAS PubMed Google Scholar
• Berthet, C., Aleem, E., Coppola, V., Tessarollo, L. & Kaldis, P. CDK2 knockout mice are viable. Curr. Biol. 13, 1775–1785 (2003).
  Article CAS PubMed Google Scholar
• Ortega, S. et al. Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nature Genet. 35, 25–31 (2003).
  Article CAS PubMed Google Scholar
• Schlegel, R. & Pardee, A. B. Caffeine-induced uncoupling of mitosis from the completion of DNA replication in mammalian cells. Science 232, 1264–1266 (1986).
  Article CAS PubMed Google Scholar
• Nishimoto, T., Ishida, R., Ajiro, K., Yamamoto, S. & Takahashi, T. The synthesis of protein(s) for chromosome condensation may be regulated by a post-transcriptional mechanism. J. Cell. Physiol. 109, 299–308 (1981).
  Article CAS PubMed Google Scholar
• Hall-Jackson, C. A., Cross, D. A., Morrice, N. & Smythe, C. ATR is a caffeine-sensitive, DNA-activated protein kinase with a substrate specificity distinct from DNA-PK. Oncogene 18, 6707–6713 (1999).
  Article CAS PubMed Google Scholar
• Sarkaria, J. N. et al. Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res. 59, 4375–4382 (1999).
  CAS PubMed Google Scholar
• Nghiem, P., Park, P., Kim, Y., Vaziri, C. & Schreiber, S. ATR inhibition selectively sensitizes G1 checkpoint-deficient cells to lethal premature chromatin condensation. Proc. Natl Acad. Sci. USA 98, 9092–9097 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Sordella, R., Bell, D. W., Haber, D. A. & Settleman, J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305, 1163–1167 (2004).
  Article CAS PubMed Google Scholar
• Lynch, T. J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129–2139 (2004).
  Article CAS PubMed Google Scholar
• Paez, J. G. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304, 1497–1500 (2004).
  Article CAS PubMed Google Scholar
• Pao, W. et al. EGF receptor gene mutations are common in lung cancers from 'never smokers' and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc. Natl Acad. Sci. USA 101, 13306–13311 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Weinstein, I. B. et al. Disorders in cell circuitry associated with multistage carcinogenesis: exploitable targets for cancer prevention and therapy. Clin. Cancer Res. 3, 2696–2702 (1997).
  CAS PubMed Google Scholar
• Weinstein, I. B. Disorders in cell circuitry during multistage carcinogenesis: the role of homeostasis. Carcinogenesis 21, 857–864 (2000).
  Article CAS PubMed Google Scholar
• Weinstein, I. B. Cancer. Addiction to oncogenes — the Achilles heal of cancer. Science 297, 63–64 (2002). References 52–54, introduced the term 'oncogene addiction'.
  Article CAS PubMed Google Scholar
• Adams, P. & Kaelin, W. J. Jr. The cellular effects of E2F overexpression. Curr. Top. Microbiol. Immunol. 208, 79–93 (1996).
  CAS PubMed Google Scholar
• Sherr, C. The Pezcoller lecture: cancer cell cycles revisited. Cancer Res. 60, 3689–3695 (2000).
  CAS PubMed Google Scholar
• Mills, G., Lu, Y. & Kohn, E. Linking molecular therapeutics to molecular diagnostics: inhibition of the FRAP/RAFT/TOR component of the PI3K pathway preferentially blocks PTEN mutant cells in vitro and in vivo. Proc. Natl Acad. Sci. USA 98, 10031–10033 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Kamb, A. Consequences of nonadaptive alterations in cancer. Mol. Biol. Cell 14, 2201–2205 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Neshat, M. et al. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc. Natl Acad. Sci. USA 98, 10314–10319 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Frei, E. D. Gene deletion: a new target for cancer chemotherapy. Lancet 342, 662–664 (1993).
  Article PubMed Google Scholar
• Cairns, P. et al. Frequency of homozygous deletion at p16/CDKN2 in primary human tumours. Nature Genet. 11, 210–212 (1995).
  Article CAS PubMed Google Scholar
• Li, W. et al. Status of methylthioadenosine phosphorylase and its impact on cellular response to L-alanosine and methylmercaptopurine riboside in human soft tissue sarcoma cells. Oncol. Res. 14, 373–379 (2004).
  Article CAS PubMed Google Scholar
• Wong, S. L. et al. Combining biological networks to predict genetic interactions. Proc. Natl Acad. Sci. USA 101, 15682–15687 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Simon, J. A. et al. Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae. Cancer Res. 60, 328–333 (2000).
  CAS PubMed Google Scholar
• Stockwell, B., Haggarty, S. & Schreiber, S. High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications. Chem. Biol. 6, 71–83 (1999). References 64 and 65 are two early examples of using isogenic cell lines to isolate compounds that kill cells in a genotype-specific manner.
  Article CAS PubMed Google Scholar
• Torrance, C., Agrawal, V., Vogelstein, B. & Kinzler, K. Use of isogenic human cancer cells for high-throughput screening and drug discovery. Nature Biotechnol. 19, 940–945 (2001).
  Article CAS Google Scholar
• Bender, A. & Pringle, J. R. Use of a screen for synthetic lethal and multicopy suppressee mutants to identify two new genes involved in morphogenesis in Saccharomyces cerevisiae. Mol. Cell. Biol. 11, 1295–1305 (1991).
  CAS PubMed PubMed Central Google Scholar
• Simons, A., Dafni, N., Dotan, I., Oron, Y. & Canaani, D. Establishment of a chemical synthetic lethality screen in cultured human cells. Genome Res. 11, 266–273 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Simons, A., Dafni, N., Dotan, I., Oron, Y. & Canaani, D. Genetic synthetic lethality screen at the single gene level in cultured human cells. Nucleic Acids Res. 29, E100 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Fantin, V. R. & Leder, P. F16, a mitochondriotoxic compound, triggers apoptosis or necrosis depending on the genetic background of the target carcinoma cell. Cancer Res. 64, 329–336 (2004).
  Article CAS PubMed Google Scholar
• Fantin, V. R., Berardi, M. J., Scorrano, L., Korsmeyer, S. J. & Leder, P. A novel mitochondriotoxic small molecule that selectively inhibits tumor cell growth. Cancer Cell 2, 29–42 (2002).
  Article CAS PubMed Google Scholar
• Wang, Y. et al. Synthetic lethal targeting of MYC by activation of the DR5 death receptor pathway. Cancer Cell 5, 501–512 (2004).
  Article CAS PubMed Google Scholar
• Haggarty, S. J., Clemons, P. A. & Schreiber, S. L. Chemical genomic profiling of biological networks using graph theory and combinations of small molecule perturbations. J. Am. Chem. Soc. 125, 10543–10545 (2003).
  Article CAS PubMed Google Scholar
• Borisy, A. A. et al. Systematic discovery of multicomponent therapeutics. Proc. Natl Acad. Sci. USA 100, 7977–7982 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46, 3–26 (2001).
  Article CAS PubMed Google Scholar
• Lipinski, C. A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods 44, 235–249 (2000).
  Article CAS PubMed Google Scholar
• Knockaert, M. et al. Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilised inhibitors. Chem. Biol. 7, 411–422 (2000).
  Article CAS PubMed Google Scholar
• Hultsch, T., Albers, M. W., Schreiber, S. L. & Hohman, R. J. Immunophilin ligands demonstrate common features of signal transduction leading to exocytosis or transcription. Proc. Natl Acad. Sci. USA 88, 6229–6233 (1991).
  Article CAS PubMed PubMed Central Google Scholar
• Baetz, K. et al. Yeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action. Proc. Natl Acad. Sci. USA 101, 4525–4230 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Giaever, G. et al. Genomic profiling of drug sensitivities via induced haploinsufficiency. Nature Genet. 21, 278–283 (1999).
  Article CAS PubMed Google Scholar
• Marton, M. et al. Drug target validation and identification of secondary drug target effects using DNA microarrays. Nature Med. 4, 1293–1301 (1998).
  Article CAS PubMed Google Scholar
• Lu, X. & Horvitz, H. R. lin-35 and lin-53, two genes that antagonize a C. elegans Ras pathway, encode proteins similar to RB and its binding protein RBAp48. Cell 95, 981–991 (1998).
  Article CAS PubMed Google Scholar
• Fay, D. S., Large, E., Han, M. & Darland, M. lin-35/Rb and ubc-18, an E2 ubiquitin-conjugating enzyme, function redundantly to control pharyngeal morphogenesis in C. elegans. Development 130, 3319–3330 (2003).
  Article CAS PubMed Google Scholar
• Fay, D. S., Keenan, S. & Han, M. fzr-1 and lin-35/Rb function redundantly to control cell proliferation in C. elegans as revealed by a nonbiased synthetic screen. Genes Dev. 16, 503–517 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Edgar, K. A. et al. Synthetic lethality of retinoblastoma mutant cells in the Drosophila eye by mutation of a novel peptidyl prolyl isomerase gene. Genetics 170, 161–171 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Kamath, R. S. et al. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421, 231–237 (2003).
  Article CAS PubMed Google Scholar
• Ashrafi, K. et al. Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421, 268–272 (2003).
  Article CAS PubMed Google Scholar
• Cherry, S. et al. Genome-wide RNAi screen reveals a specific sensitivity of IRES-containing RNA viruses to host translation inhibition. Genes Dev. 19, 445–452 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Rual, J. F. et al. Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res. 14, 2162–2168 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Willingham, A. T., Deveraux, Q. L., Hampton, G. M. & Aza-Blanc, P. RNAi and HTS: exploring cancer by systematic loss-of-function. Oncogene 23, 8392–8400 (2004).
  Article CAS PubMed Google Scholar
• Elbashir, S. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498 (2001).
  Article CAS PubMed Google Scholar
• Brummelkamp, T. R., Bernards, R. & Agami, R. Stable suppression of tumorigenicity by virus-mediated RNA interference. Cancer Cell 2, 243–247 (2002).
  Article CAS PubMed Google Scholar
• Brummelkamp, T. R., Bernards, R. & Agami, R. A system for stable expression of short interfering RNAs in mammalian cells. Science 296, 550–553 (2002).
  Article CAS PubMed Google Scholar
• Lee, N. S. et al. Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nature Biotechnol. 20, 500–505 (2002).
  Article CAS Google Scholar
• Paddison, P. J., Caudy, A. A., Bernstein, E., Hannon, G. J. & Conklin, D. S. Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev. 16, 948–958 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Sui, G. et al. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc. Natl Acad. Sci. USA 99, 5515–5520 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Berns, K. et al. A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428, 431–437 (2004).
  Article CAS PubMed Google Scholar
• Paddison, P. J. et al. A resource for large-scale RNA-interference-based screens in mammals. Nature 428, 427–431 (2004). References 97 and 98 suggest that it should eventually be possible to carry out synthetic lethal screens in isogenic human cell-line pairs using bar-coded shRNA libraries.
  Article CAS PubMed Google Scholar
• Shirane, D. et al. Enzymatic production of RNAi libraries from cDNAs. Nature Genet. 36, 190–196 (2004).
  Article CAS PubMed Google Scholar
• Aza-Blanc, P. et al. Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening. Mol. Cell 12, 627–637 (2003).
  Article CAS PubMed Google Scholar
• Gorre, M. et al. Clinical resistance to STI-571 cancer therapy caused by BCR_–_ABL gene mutation or amplification. Science 293, 876–880 (2001).
  Article CAS PubMed Google Scholar
• Shah, N. P. et al. L. Multiple BCR–ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2, 117–125 (2002).
  Article CAS PubMed Google Scholar
• Jonkers, J. & Berns, A. Oncogene addiction: sometimes a temporary slavery. Cancer Cell 6, 535–538 (2004).
  CAS PubMed Google Scholar
• Bailey, S. N., Sabatini, D. M. & Stockwell, B. R. Microarrays of small molecules embedded in biodegradable polymers for use in mammalian cell-based screens. Proc. Natl Acad. Sci. USA 101, 16144–16149 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Wheeler, D. B. et al. RNAi living-cell microarrays for loss-of-function screens in Drosophila melanogaster cells. Nature Methods 1, 127–132 (2004).
  Article CAS PubMed Google Scholar
• Ooi, S. L., Shoemaker, D. D. & Boeke, J. D. DNA helicase gene interaction network defined using synthetic lethality analyzed by microarray. Nature Genet. 35, 277–286 (2003). Describes the use of DNA bar codes coupled with oligonucleotide microarrays to conduct synthetic lethal assays in yeast.
  Article CAS PubMed Google Scholar
• Shoemaker, D. D., Lashkari, D. A., Morris, D., Mittmann, M. & Davis, R. W. Quantitative phenotypic analysis of yeast deletion mutants using a highly parallel molecular bar-coding strategy. Nature Genet. 14, 450–456 (1996).
  Article CAS PubMed Google Scholar
• Winzeler, E. A. et al. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901–906 (1999).
  Article CAS PubMed Google Scholar
• Eason, R. G. et al. Characterization of synthetic DNA bar codes in Saccharomyces cerevisiae gene-deletion strains. Proc. Natl Acad. Sci. USA 101, 11046–11051 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Hensel, M. et al. Simultaneous identification of bacterial virulence genes by negative selection. Science 269, 400–403 (1995).
  Article CAS PubMed Google Scholar