Towards a compendium of essential genes-From model organisms to synthetic lethality in cancer cells

Critical Reviews in Biochemistry and Molecular Biology

Volumn 51, Issue 2, 2016, Pages 74-85

  Zhan, Tianzuo ^a,b   Boutros, Michael ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

Cancer research; CRISPR Cas9; essential genes; genetic interaction; RNAi; screening; synthetic lethality

Indexed keywords

BIOINFORMATICS; CAENORHABDITIS ELEGANS; CANCER CELL; CANCER RESEARCH; CELL DEATH; CRISPR CAS SYSTEM; ESSENTIAL GENE; GENE IDENTIFICATION; GENE INTERACTION; GENETIC SCREENING; GENOME; NONHUMAN; PRIORITY JOURNAL; REVIEW; SACCHAROMYCES CEREVISIAE; TRANSCRIPTION INITIATION; ANIMAL; BIOLOGICAL MODEL; BIOLOGY; GENETICS; HUMAN; NEOPLASM; PATHOLOGY;

ANIMALS; COMPUTATIONAL BIOLOGY; GENES, ESSENTIAL; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS;

EID: 84948763828     PISSN: 10409238     EISSN: 15497798     Source Type: Journal    
DOI: 10.3109/10409238.2015.1117053     Document Type: Review

References (153)

1. Adams MD. (2000). The genome sequence of Drosophila melanogaster. Science 287: 2185-95
2. Amsterdam A, Nissen RM, Sun Z, et al. (2004). Identification of 315 genes essential for early zebrafish development. Proc Natl Acad Sci USA 101: 12792-7
3. Antal CE, Hudson AM, Kang E, et al. (2015). Cancer-associated protein kinase C mutations reveal kinases role as tumor suppressor. Cell 160: 489-502
4. Astsaturov I, Ratushny V, Sukhanova A, et al. (2010). Synthetic lethal screen of an EGFR-centered network to improve targeted therapies. Sci Signal 3: ra67
5. Audeh MW, Carmichael J, Penson RT, et al. (2010). Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet (London, England) 376: 245-51
6. Babij C, Zhang Y, Kurzeja RJ, et al. (2011). STK33 kinase activity is nonessential in KRAS-dependent cancer cells. Cancer Res 71: 5818-26
7. Balling R. (2001). ENU mutagenesis: analyzing gene function in mice. Annu Rev Genomics Hum Genet 2: 463-92
8. Barbie DA, Tamayo P, Boehm JS, et al. (2009). Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462: 108-12
9. Baudin A, Ozier-Kalogeropoulos O, Denouel A, et al. (1993). A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae. Nucleic Acids Res 21: 3329-30
10. Bellen HJ, Levis RW, Liao G, et al. (2004). The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167: 761-81
11. Blake JA, Bult CJ, Eppig JT, et al. (2014). The Mouse Genome Database: integration of and access to knowledge about the laboratory mouse. Nucleic Acids Res 42: D810-17
12. Bommi-Reddy A, Almeciga I, Sawyer J, et al. (2008). Kinase requirements in human cells: III. Altered kinase requirements in VHL-/-cancer cells detected in. A pilot synthetic lethal screen. Proc Natl Acad Sci USA 105: 16484-9
13. Boone C, Bussey H, Andrews BJ. (2007). Exploring genetic interactions and networks with yeast. Nat Rev Genet 8: 437-49
14. Bourbon HM, Gonzy-Treboul G, Peronnet F, et al. (2002). A P-insertion screen identifying novel X-linked essential genes in Drosophila. Mech Dev 110: 71-83
15. Boutros M, Ahringer J. (2008). The art and design of genetic screens: RNA interference. Nat Rev Genet 9: 554-66
16. Boutros M, Kiger AA, Armknecht S, et al. (2004). Genome-wide RNAi analysis of growth and viability in Drosophila cells. Science 303: 832-5
17. Bradley A, Anastassiadis K, Ayadi A, et al. (2012). The mammalian gene function resource: the International Knockout Mouse Consortium. Mamm Genome 23: 580-6
18. Breslow DK, Cameron DM, Collins SR, et al. (2008). A comprehensive strategy enabling high-resolution functional analysis of the yeast genome. Nat. Methods 5: 711-18
19. Bryant HE, Schultz N, Thomas HD, et al. (2005). Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434: 913-17
20. Chan DA, Giaccia AJ. (2011). Harnessing synthetic lethal interactions in anticancer drug discovery. Nat Rev Drug Discov 10: 351-64
21. Chen WH, Minguez P, Lercher MJ, Bork P. (2012). OGEE: an online gene essentiality database. Nucleic Acids Res 40: D901-6
22. Cheung HW, Cowley GS, Weir BA, et al. (2011). Systematic investigation of genetic vulnerabilities across cancer cell lines reveals lineage-specific dependencies in ovarian cancer. Proc Natl Acad Sci USA 108: 12372-7
23. Clark DV, Rogalski TM, Donati LM, Baillie DL. (1988). The unc-22(IV) region of Caenorhabditis elegans: genetic analysis of lethal mutations. Genetics 119: 345-53
24. Clatworthy AE, Pierson E, Hung DT. (2007). Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol 3: 541-8
25. Cong L, Ran FA, Cox D, et al. (2013). Multiplex genome engineering using CRISPR/Cas systems. Science 339: 819-23
26. Cowley GS, Weir BA, Vazquez F, et al. (2014). Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies. Sci Data 1: 140035
27. Curran SP, Ruvkun G. (2007). Lifespan regulation by evolutionarily conserved genes essential for viability. PLoS Genet 3: e56
28. Davierwala AP, Haynes J, Li Z, et al. (2005). The synthetic genetic interaction spectrum of essential genes. Nat Genet 37: 1147-52
29. de Berardinis V, Vallenet D, Castelli V, et al. (2008). A complete collection of single-gene deletion mutants of Acinetobacter baylyi ADP1. Mol Syst Biol 4: 174
30. Deak P, Omar MM, Saunders R, et al. (1997). P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: correlation of physical and cytogenetic maps in chromosomal region 86E-87F. Genetics 147: 1697-722
31. Deutschbauer AM, Jaramillo DF, Proctor M, et al. (2005). Mechanisms of haploinsufficiency revealed by genome-wide profiling in yeast. Genetics 169: 1915-25
32. Dickerson JE, Zhu A, Robertson DL, Hentges KE. (2011). Defining the role of essential genes in human disease. PLoS One 6: e27368
33. Dietlein F, Thelen L, Jokic M, et al. (2014). A functional cancer genomics screen identifies a druggable synthetic lethal interaction between MSH3 and PRKDC. Cancer Discov 4: 592-605
34. Dietzl G, Chen D, Schnorrer F, et al. (2007). A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448: 151-6
35. Dolma S, Lessnick SL, Hahn WC, Stockwell BR. (2003). Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3: 285-96
36. Dos Santos G, Schroeder AJ, Goodman JL, et al. (2015). FlyBase: introduction of the Drosophila melanogaster Release 6 reference genome assembly and large-scale migration of genome annotations. Nucleic Acids Res 43: D690-7
37. Driever W, Solnica-Krezel L, Schier AF, et al. (1996). A genetic screen for mutations affecting embryogenesis in zebrafish. Development 123: 37-46
38. Farmer H, McCabe N, Lord CJ, et al. (2005). Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434: 917-21
39. Fischer B, Sandmann T, Horn T, et al. (2015). A map of directional genetic interactions in a metazoan cell. Elife 4. doi: 10.7554/eLife.05464
40. Fong PC, Boss DS, Yap TA, et al. (2009). Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361: 123-34
41. Fraser AG, Kamath RS, Zipperlen P, et al. (2000). Functional genomic analysis of C. Elegans chromosome I by systematic RNA interference. Nature 408: 325-30
42. Friedland AE, Tzur YB, Esvelt KM, et al. (2013). Heritable genome editing in C. Elegans via a CRISPR-Cas9 system. Nat Methods 10: 741-3
43. Gaiano N, Amsterdam A, Kawakami K, et al. (1996). Insertional mutagenesis and rapid cloning of essential genes in zebrafish. Nature 383: 829-32
44. Galiana-Arnoux D, Dostert C, Schneemann A, et al. (2006). Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila. Nat Immunol 7: 590-7
45. Garber K. (2002). Synthetic lethality: killing cancer with cancer. J Natl Cancer Inst 94: 1666-8
46. Gazit R, Gruda R, Elboim M, et al. (2006). Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1. Nat Immunol 7: 517-23
47. Georgi B, Voight BF, Bućan M. (2013). From mouse to human: evolutionary genomics analysis of human orthologs of essential genes. PLoS Genet 9: e1003484
48. Gerdes SY, Scholle MD, Campbell JW, et al. (2003). Experimental determination and system level analysis of essential genes in Escherichia coli MG1655. J. Bacteriol 185: 5673-84
49. Giaever G, Chu AM, Ni L, et al. (2002). Functional profiling of the Saccharomyces cerevisiae genome. Nature 418: 387-91
50. Gilbert LA, Horlbeck MA, Adamson B, et al. (2014). Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159: 647-61
51. Gillies RJ, Verduzco D, Gatenby RA. (2012). Evolutionary dynamics of carcinogenesis and why targeted therapy does not work. Nat Rev Cancer 12: 487-93
52. Glass JI, Assad-Garcia N, Alperovich N, et al. (2006). Essential genes of a minimal bacterium. Proc Natl Acad Sci USA 103: 425-30
53. Gluecksohn-Waelsch S. (1963). Lethal genes and analysis of differentiation. Science 142: 1269-76
54. Golling G, Amsterdam A, Sun Z, et al. (2002). Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development. Nat Genet 31: 135-40
55. Gönczy P, Echeverri C, Oegema K, et al. (2000). Functional genomic analysis of cell division in C. Elegans using RNAi of genes on chromosome III. Nature 408: 331-6
56. Gratz SJ, Cummings AM, Nguyen JN, et al. (2013). Genome engineering of Drosophila with the CRISPR RNA-guided Cas9 nuclease. Genetics 194: 1029-35
57. Gustafson AM, Snitkin ES, Parker SCJ, et al. (2006). Towards the identification of essential genes using targeted genome sequencing and comparative analysis. BMC Genomics 7: 265
58. Haffter P, Granato M, Brand M, et al. (1996). The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 123: 1-36
59. Harborth J, Elbashir SM, Bechert K, et al. (2001). Identification of essential genes in cultured mammalian cells using small interfering RNAs. J Cell Sci 114: 4557-65
60. Harris TW, Baran J, Bieri T, et al. (2014). WormBase 2014: new views of curated biology. Nucleic Acids Res 42: D789-93
61. Hart T, Brown KR, Sircoulomb F, et al. (2014). Measuring error rates in genomic perturbation screens: gold standards for human functional genomics. Mol Syst Biol 10: 733
62. Hart T, Chandrashekhar M, Aregger M, et al. (2015). Systematic discovery and classification of human cell line essential genes, bioRxiv. Cold Spring Harbor Labs J. doi: 10.1101/015412
63. Herrmann T, van der Hoeven F, Grone HJ, et al. (2003). Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy. J Cell Biol 161: 1105-15
64. Hillenmeyer ME, Fung E, Wildenhain J, et al. (2008). The chemical genomic portrait of yeast: uncovering a phenotype for all genes. Science 320: 362-5
65. Hillier LW, Marth GT, Quinlan AR, et al. (2008). Whole-genome sequencing and variant discovery in C. Elegans. Nat Methods 5: 183-8
66. Ho TT, Zhou N, Huang J, et al. (2015). Targeting non-coding RNAs with the CRISPR/Cas9 system in human cell lines. Nucleic Acids Res 43: e17
67. Horn T, Sandmann T, Fischer B, et al. (2011). Mapping of signaling networks through synthetic genetic interaction analysis by RNAi. Nat Methods 8: 341-6
68. Howe K, Clark MD, Torroja CF, et al. (2013). The zebrafish reference genome sequence and its relationship to the human genome. Nature 496: 498-503
69. Hrabé de Angelis MH, Flaswinkel H, Fuchs H, et al. (2000). Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet 25: 444-7
70. Hwang WY, Fu Y, Reyon D, et al. (2013). Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol 31: 227-9
71. Jeong H, Mason SP, Barabási AL, Oltvai ZN. (2001). Lethality and centrality in protein networks. Nature 411: 41-2
72. Johnsen RC, Baillie DL. (1991). Genetic analysis of a major segment [LGV(left)] of the genome of Caenorhabditis elegans. Genetics 129: 735-52
73. Juhas M, Eberl L, Glass JI. (2011). Essence of life: essential genes of minimal genomes. Trends Cell Biol 21: 562-8
74. Justice MJ. (1999). Mouse ENU mutagenesis. Hum Mol Genet 8: 1955-63
75. Kaelin WG. (2005). The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer 5: 689-98
76. Kamath RS, Fraser AG, Dong Y, et al. (2003). Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421: 231-7
77. Kantarjian H, Sawyers C, Hochhaus A, et al. (2002). Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346: 645-52
78. Kearns NA, Pham H, Tabak B, et al. (2015). Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nat Methods 12: 401-3
79. Khalil AS, Collins JJ. (2010). Synthetic biology: applications come of age. Nat Rev Genet 11: 367-79
80. Kim DU, Hayles J, Kim D, et al. (2010). Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe. Nat Biotechnol 28: 617-23
81. Kittler R, Putz G, Pelletier L, et al. (2004). An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division. Nature 432: 1036-40
82. Kobayashi K, Ehrlich SD, Albertini A, et al. (2003). Essential Bacillus subtilis genes. Proc Natl Acad Sci USA 100: 4678-83
83. Koh JLY, Brown KR, Sayad A, et al. (2012). COLT-Cancer: functional genetic screening resource for essential genes in human cancer cell lines. Nucleic Acids Res 40: D957-63
84. Koike-Yusa H, Li Y, Tan EP, et al. (2014). Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat Biotechnol 32: 267-73
85. Konermann S, Brigham MD, Trevino AE, et al. (2014). Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517: 583-8
86. Krastev DB, Slabicki M, Paszkowski-Rogacz M, et al. (2011). A systematic RNAi synthetic interaction screen reveals a link between p53 and snoRNP assembly. Nat Cell Biol 13: 809-18
87. Krylov DM, Wolf YI, Rogozin IB, Koonin EV. (2003). Gene loss, protein sequence divergence, gene dispensability, expression level, and interactivity are correlated in eukaryotic evolution. Genome Res 13: 2229-35
88. Lallemand-Breitenbach V, Guillemin MC, Janin A, et al. (1999). Retinoic acid and arsenic synergize to eradicate leukemic cells in a mouse model of acute promyelocytic leukemia. J Exp Med 189: 1043-52
89. Lenz LS, Marx J, Chamulitrat W, et al. (2011). Adipocyte-specific inactivation of Acyl-CoA synthetase fatty acid transport protein 4 (Fatp4) in mice causes adipose hypertrophy and alterations in metabolism of complex lipids under high fat diet. J Biol Chem 286: 35578-87
90. Liang H, Li WH. (2007). Gene essentiality, gene duplicability and protein connectivity in human and mouse. Trends Genet 23: 375-8
91. Liao BY, Zhang J. (2007). Mouse duplicate genes are as essential as singletons. Trends Genet 23: 378-81
92. Liu-Sullivan N, Zhang J, Bakleh A, et al. (2011). Pooled shRNA screen for sensitizers to inhibition of the mitotic regulator polo-like kinase (PLK1). Oncotarget 2: 1254-64
93. Lo-Coco F, Avvisati G, Vignetti M, et al. (2013). Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 369: 111-21
94. Luo B, Cheung HW, Subramanian A, et al. (2008). Highly parallel identification of essential genes in cancer cells. Proc Natl Acad Sci USA 105: 20380-5
95. Luo H, Lin Y, Gao F, et al. (2013). DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements. Nucleic Acids Res 42: D574-80
96. Luo T, Masson K, Jaffe JD, et al. (2012). STK33 kinase inhibitor BRD-8899 has no effect on KRAS-dependent cancer cell viability. Proc Natl Acad Sci USA 109: 2860-5
97. Ma Y, Creanga A, Lum L, Beachy PA. (2006). Prevalence of off-target effects in Drosophila RNA interference screens. Nature 443: 359-63
98. Maeda I, Kohara Y, Yamamoto M, Sugimoto A. (2001). Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Curr Biol 11: 171-6
99. Mali P, Yang L, Esvelt KM, et al. (2013). RNA-guided human genome engineering via Cas9. Science 339: 823-6
100. Marcotte R, Brown KR, Suarez F, et al. (2012). Essential gene profiles in breast, pancreatic, and ovarian cancer cells. Cancer Discov 2: 172-89
101. Matsui M, Oshima M, Oshima H, et al. (1996). Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene. Dev Biol 178: 179-85
102. Mnaimneh S, Davierwala AP, Haynes J, et al. (2004). Exploration of essential gene functions via titratable promoter alleles. Cell 118: 31-44
103. Moffat J, Grueneberg DA, Yang X, et al. (2006). A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124: 1283-98
104. Mohni KN, Kavanaugh GM, Cortez D. (2014). ATR pathway inhibition is synthetically lethal in cancer cells with ERCC1 deficiency. Cancer Res 74: 2835-45
105. Ngo VN, Davis RE, Lamy L, et al. (2006). A loss-of-function RNA interference screen for molecular targets in cancer. Nature 441: 106-10
106. Nijhawan D, Zack TI, Ren Y, et al. (2012). Cancer vulnerabilities unveiled by genomic loss. Cell 150: 842-54
107. Nolan PM, Peters J, Strivens M, et al. (2000a). A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse. Nat Genet 25: 440-3
108. Nolan PM, Peters J, Vizor L, et al. (2000b). Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource. Mamm Genome 11: 500-6
109. Oh SW, Kingsley T, Shin H, et al. (2003). A P-element insertion screen identified mutations in 455 novel essential genes in Drosophila. Genetics 163: 195-201
110. Otto SP, Lenormand T. (2002). Resolving the paradox of sex and recombination. Nat Rev Genet 3: 252-61
111. Park D, Park J, Park SG, et al. (2008). Analysis of human disease genes in the context of gene essentiality. Genomics 92: 414-18
112. Patton EE, Zon LI. (2001). The art and design of genetic screens: zebrafish. Nat Rev Genet 2: 956-66
113. Peter A, Schöttler P, Werner M, et al. (2002). Mapping and identification of essential gene functions on the X chromosome of Drosophila. EMBO Rep 3: 34-8
114. Ramani AK, Chuluunbaatar T, Verster AJ, et al. (2012). The majority of animal genes are required for wild-type fitness. Cell 148: 792-802
115. Rinchik EM, Carpenter DA. (1993). N-ethyl-N-nitrosourea-induced prenatally lethal mutations define at least two complementation groups within the embryonic ectoderm development (EED) locus in mouse Chromosome 7. Mamm Genome 4: 349-53
116. Rosenbluh J, Nijhawan D, Cox AG, et al. (2012). β-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis. Cell 151: 1457-73
117. Russell WL, Kelly EM, Hunsicker PR, et al. (1979). Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. Proc Natl Acad Sci USA 76: 5818-19
118. Schlabach MR, Luo J, Solimini NL, et al. (2008). Cancer proliferation gene discovery through functional genomics. Science 319: 620-4
119. Scholl C, Fröhling S, Dunn IF, et al. (2009). Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell 137: 821-34
120. Scott CL, Swisher EM, Kaufmann SH. (2015). Poly (ADP-Ribose) polymerase inhibitors: recent advances and future development. J Clin Oncol 33: 1397-406
121. Shaffer AL, Emre NCT, Lamy L, et al. (2008). IRF4 addiction in multiple myeloma. Nature 454: 226-31
122. Shalem O, Sanjana NE, Hartenian E, et al. (2014). Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343: 84-7
123. Shalem O, Sanjana NE, Zhang F. (2015). High-throughput functional genomics using CRISPR-Cas9. Nat Rev Genet 16: 299-311
124. Shao W, Fanelli M, Ferrara FF, et al. (1998). Arsenic trioxide as an inducer of apoptosis and loss of PML/RAR alpha protein in acute promyelocytic leukemia cells. J Natl Cancer Inst 90: 124-33
125. Shim J, Moulson CL, Newberry EP, et al. (2009). Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice. J Lipid Res 50: 491-500
126. Shirasawa S, Furuse M, Yokoyama N, Sasazuki T. (1993). Altered growth of human colon cancer cell lines disrupted at activated Ki-ras. Science 260: 85-8
127. Silva JM, Marran K, Parker JS, et al. (2008). Profiling essential genes in human mammary cells by multiplex RNAi screening. Science 319: 617-20
128. Simons A, Dafni N, Dotan I, et al. (2001). Establishment of a chemical synthetic lethality screen in cultured human cells. Genome Res 11: 266-73
129. Skarnes WC, Rosen B, West AP, et al. (2011). A conditional knockout resource for the genome-wide study of mouse gene function. Nature 474: 337-42
130. Sönnichsen B, Koski LB, Walsh A, et al. (2005). Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434: 462-9
131. Straussman R, Morikawa T, Shee K, et al. (2012). Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 487: 500-4
132. Tang T, Li L, Tang J, et al. (2010). A mouse knockout library for secreted and transmembrane proteins. Nat Biotechnol 28: 749-55
133. Thomas KR, Capecchi MR. (1987). Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51: 503-12
134. Tong AH, Evangelista M, Parsons AB, et al. (2001). Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science 294: 2364-8
135. Tong AHY, Lesage G, Bader GD, et al. (2004). Global mapping of the yeast genetic interaction network. Science 303: 808-13
136. Turner NC, Lord CJ, Iorns E, et al. (2008). A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor. EMBO J 27: 1368-77
137. Tutt A, Robson M, Garber JE, et al. (2010). Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet (London, England) 376: 235-44
138. van der Meer R, Song HY, Park SH, et al. (2014). RNAi screen identifies a synthetic lethal interaction between PIM1 overexpression and PLK1 inhibition. Clin Cancer Res 20: 3211-21
139. Varfolomeev EE, Schuchmann M, Luria V, et al. (1998). Targeted disruption of the mouse caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity 9: 267-76
140. Venter JC, Adams MD, Myers EW, et al. (2001). The sequence of the human genome. Science 291: 1304-51
141. Vizeacoumar FJ, Arnold R, Vizeacoumar FS, et al. (2013). A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities. Mol Syst Biol 9: 696
142. Wang T, Wei JJ, Sabatini DM, Lander ES. (2014). Genetic screens in human cells using the CRISPR-Cas9 system. Science 343: 80-4
143. Weinstein IB, Joe A. (2008). Oncogene addiction. Cancer Res 68: 3077-80; discussion 3080
144. Weïwer M, Spoonamore J, Wei J, et al. (2012). A potent and selective quinoxalinone-based STK33 inhibitor does not show synthetic lethality in KRAS-dependent cells. ACS Med Chem Lett 3: 1034-8
145. White JK, Gerdin AK, Karp NA, et al. (2013). Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes. Cell 154: 452-64
146. Whitehurst AW, Bodemann BO, Cardenas J, et al. (2007). Synthetic lethal screen identification of chemosensitizer loci in cancer cells. Nature 446: 815-19
147. Wilding JL, Bodmer WF. (2014). Cancer cell lines for drug discovery and development. Cancer Res 74: 2377-84
148. Winzeler EA, Shoemaker DD, Astromoff A, et al. (1999). Functional characterization of the S. Cerevisiae genome by gene deletion and parallel analysis. Science 285: 901-6
149. Wood V, Gwilliam R, Rajandream MA, et al. (2002). The genome sequence of Schizosaccharomyces pombe. Nature 415: 871-80
150. Yin Y, Yan P, Lu J, et al. (2015). Opposing roles for the lncRNA haunt and its genomic locus in regulating HOXA gene activation during embryonic stem cell differentiation. Cell Stem Cell 16: 504-16
151. Yu H, Greenbaum D, Xin Lu H, et al. (2004). Genomic analysis of essentiality within protein networks. Trends Genet 20: 227-31
152. Zhou Y, Zhu S, Cai C, et al. (2014). High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells. Nature 509: 487-91
153. Zuber J, Shi J, Wang E, et al. (2011). RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478: 524-8