A functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system

BMC Genomics

Volumn 15, Issue 1, 2014, Pages

  Schlecht, Ulrich ^a   Suresh, Sundari ^a   Xu, Weihong ^a   Aparicio, Ana M ^a   Chu, Angela ^a   Proctor, Michael J ^a   Davis, Ronald W ^a   Scharfe, Curt ^a   St Onge, Robert P ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Copper; Disulfiram; Elesclomol; Functional Genomics; Iron; Menkes; Vacuole; Wilson's; Yeast

Indexed keywords

COPPER; COPPER SULFATE; DISULFIRAM; ELESCLOMOL;

ACIDITY; ARTICLE; CARBON SOURCE; CELL VACUOLE; COLONY FORMING UNIT; COPPER DEFICIENCY; COPPER METABOLISM; CULTURE MEDIUM; ENERGY METABOLISM; FUNCTIONAL GENOMICS; FUNGAL STRAIN; FUNGAL VIABILITY; FUNGUS GROWTH; GENE DELETION; GENE MUTATION; HOMOZYGOSITY; HUMAN; IRON TRANSPORT; MENKES SYNDROME; NONHUMAN; NUCLEOTIDE SEQUENCE; OXIDATIVE PHOSPHORYLATION; PHENOTYPE; WILSON DISEASE;

CELL RESPIRATION; CLUSTER ANALYSIS; COPPER; CULTURE MEDIA; DISULFIRAM; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, FUNGAL; GENE REGULATORY NETWORKS; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; HOMEOSTASIS; HUMANS; HYDRAZINES; HYDROGEN-ION CONCENTRATION; PHENOTYPE; VACUOLES; YEASTS;

EID: 84899489656     PISSN: None     EISSN: 14712164     Source Type: Journal    
DOI: 10.1186/1471-2164-15-263     Document Type: Article

References (80)

1. Kim BE, Nevitt T, Thiele DJ. Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol 2008, 4(3):176-185. 10.1038/nchembio.72, 18277979.
2. Horn D, Barrientos A. Mitochondrial copper metabolism and delivery to cytochrome c oxidase. IUBMB Life 2008, 60(7):421-429. 10.1002/iub.50, 2864105, 18459161.
3. Valentine JS, Doucette PA, Zittin Potter S. Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis. Annu Rev Biochem 2005, 74:563-593. 10.1146/annurev.biochem.72.121801.161647, 15952898.
4. Furukawa Y, Torres AS, O'Halloran TV. Oxygen-induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS. Embo J 2004, 23(14):2872-2881. 10.1038/sj.emboj.7600276, 1150991, 15215895.
5. Hellman NE, Gitlin JD. Ceruloplasmin metabolism and function. Annu Rev Nutr 2002, 22:439-458. 10.1146/annurev.nutr.22.012502.114457, 12055353.
6. Stearman R, Yuan DS, Yamaguchi-Iwai Y, Klausner RD, Dancis A. A permease-oxidase complex involved in high-affinity iron uptake in yeast. Science 1996, 271(5255):1552-1557. 10.1126/science.271.5255.1552, 8599111.
7. De Silva DM, Askwith CC, Eide D, Kaplan J. The FET3 gene product required for high affinity iron transport in yeast is a cell surface ferroxidase. J Biol Chem 1995, 270(3):1098-1101. 10.1074/jbc.270.3.1098, 7836366.
8. Robinson NJ, Winge DR. Copper metallochaperones. Annu Rev Biochem 2010, 79:537-562. 10.1146/annurev-biochem-030409-143539, 3986808, 20205585.
9. Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson's disease. Lancet 2007, 369(9559):397-408. 10.1016/S0140-6736(07)60196-2, 17276780.
10. Menkes JH, Alter M, Steigleder GK, Weakley DR, Sung JH. A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Pediatrics 1962, 29:764-779.
11. De Bie P, Muller P, Wijmenga C, Klomp LW. Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. J Med Genet 2007, 44(11):673-688. 10.1136/jmg.2007.052746, 2752173, 17717039.
12. Horng YC, Leary SC, Cobine PA, Young FB, George GN, Shoubridge EA, Winge DR. Human Sco1 and Sco2 function as copper-binding proteins. J Biol Chem 2005, 280(40):34113-34122. 10.1074/jbc.M506801200, 16091356.
13. Leary SC, Cobine PA, Kaufman BA, Guercin GH, Mattman A, Palaty J, Lockitch G, Winge DR, Rustin P, Horvath R, Shoubridge EA. The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. Cell Metab 2007, 5(1):9-20. 10.1016/j.cmet.2006.12.001, 17189203.
14. Leary SC, Kaufman BA, Pellecchia G, Guercin GH, Mattman A, Jaksch M, Shoubridge EA. Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase. Hum Mol Genet 2004, 13(17):1839-1848. 10.1093/hmg/ddh197, 15229189.
15. Bestwick M, Jeong MY, Khalimonchuk O, Kim H, Winge DR. Analysis of Leigh syndrome mutations in the yeast SURF1 homolog reveals a new member of the cytochrome oxidase assembly factor family. Mol Cell Biol 2010, 30(18):4480-4491. 10.1128/MCB.00228-10, 2937524, 20624914.
16. Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V, Munnich A, Bonnefont JP, Rustin P, Rotig A. Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy. Am J Hum Genet 2000, 67(5):1104-1109. 1288552, 11013136.
17. Horvath R, Lochmuller H, Stucka R, Yao J, Shoubridge EA, Kim SH, Gerbitz KD, Jaksch M. Characterization of human SCO1 and COX17 genes in mitochondrial cytochrome-c-oxidase deficiency. Biochem Biophys Res Commun 2000, 276(2):530-533. 10.1006/bbrc.2000.3495, 11027508.
18. Papadopoulou LC, Sue CM, Davidson MM, Tanji K, Nishino I, Sadlock JE, Krishna S, Walker W, Selby J, Glerum DM, Coster RV, Lyon G, Scalais E, Lebel R, Kaplan P, Shanske S, De Vivo DC, Bonilla E, Hirano M, DiMauro S, Schon EA. Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. Nat Genet 1999, 23(3):333-337. 10.1038/15513, 10545952.
19. Jaksch M, Ogilvie I, Yao J, Kortenhaus G, Bresser HG, Gerbitz KD, Shoubridge EA. Mutations in SCO2 are associated with a distinct form of hypertrophic cardiomyopathy and cytochrome c oxidase deficiency. Hum Mol Genet 2000, 9(5):795-801. 10.1093/hmg/9.5.795, 10749987.
20. Desai V, Kaler SG. Role of copper in human neurological disorders. Am J Clin Nutr 2008, 88(3):855S-858S.
21. Strozyk D, Launer LJ, Adlard PA, Cherny RA, Tsatsanis A, Volitakis I, Blennow K, Petrovitch H, White LR, Bush AI. Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid. Neurobiol Aging 2009, 30(7):1069-1077. 10.1016/j.neurobiolaging.2007.10.012, 2709821, 18068270.
22. Fox JH, Kama JA, Lieberman G, Chopra R, Dorsey K, Chopra V, Volitakis I, Cherny RA, Bush AI, Hersch S. Mechanisms of copper ion mediated Huntington's disease progression. PLoS One 2007, 2(3):e334. 10.1371/journal.pone.0000334, 1828629, 17396163.
23. Rasia RM, Bertoncini CW, Marsh D, Hoyer W, Cherny D, Zweckstetter M, Griesinger C, Jovin TM, Fernandez CO. Structural characterization of copper(II) binding to alpha-synuclein: Insights into the bioinorganic chemistry of Parkinson's disease. Proc Natl Acad Sci U S A 2005, 102(12):4294-4299. 10.1073/pnas.0407881102, 555498, 15767574.
24. De Freitas J, Wintz H, Kim JH, Poynton H, Fox T, Vulpe C. Yeast, a model organism for iron and copper metabolism studies. Biometals 2003, 16(1):185-197. 10.1023/A:1020771000746, 12572678.
25. Askwith C, Kaplan J. Iron and copper transport in yeast and its relevance to human disease. Trends Biochem Sci 1998, 23(4):135-138. 10.1016/S0968-0004(98)01192-X, 9584616.
26. Diaz-Ruiz R, Uribe-Carvajal S, Devin A, Rigoulet M. Tumor cell energy metabolism and its common features with yeast metabolism. Biochim Biophys Acta 2009, 1796(2):252-265.
27. Rossignol R, Gilkerson R, Aggeler R, Yamagata K, Remington SJ, Capaldi RA. Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res 2004, 64(3):985-993. 10.1158/0008-5472.CAN-03-1101, 14871829.
28. St Onge R, Schlecht U, Scharfe C, Evangelista M. Forward chemical genetics in yeast for discovery of chemical probes targeting metabolism. Molecules 2012, 17(11):13098-13115. 3539408, 23128089.
29. Hillenmeyer ME, Fung E, Wildenhain J, Pierce SE, Hoon S, Lee W, Proctor M, St Onge RP, Tyers M, Koller D, Altman RB, Davis RW, Nislow C, Giaever G. The chemical genomic portrait of yeast: uncovering a phenotype for all genes. Science 2008, 320(5874):362-365. 10.1126/science.1150021, 2794835, 18420932.
30. Lee W, St Onge RP, Proctor M, Flaherty P, Jordan MI, Arkin AP, Davis RW, Nislow C, Giaever G. Genome-wide requirements for resistance to functionally distinct DNA-damaging agents. PLoS Genet 2005, 1(2):e24. 10.1371/journal.pgen.0010024, 1189734, 16121259.
31. Steinmetz LM, Scharfe C, Deutschbauer AM, Mokranjac D, Herman ZS, Jones T, Chu AM, Giaever G, Prokisch H, Oefner PJ, Davis RW. Systematic screen for human disease genes in yeast. Nat Genet 2002, 31(4):400-404.
32. Giaever G, Chu AM, Ni L, Connelly C, Riles L, Veronneau S, Dow S, Lucau-Danila A, Anderson K, Andre B, Arkin AP, Astromoff A, El-Bakkoury M, Bangham R, Benito R, Brachat S, Campanaro S, Curtiss M, Davis K, Deutschbauer A, Entian KD, Flaherty P, Foury F, Garfinkel DJ, Gerstein M, Gotte D, Güldener U, Hegemann JH, Hempel S, Herman Z, et al. Functional profiling of the Saccharomyces cerevisiae genome. Nature 2002, 418(6896):387-391. 10.1038/nature00935, 12140549.
33. Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K, Andre B, Bangham R, Benito R, Boeke JD, Bussey H, Chu AM, Connelly C, Davis K, Dietrich F, Dow SW, El Bakkoury M, Foury F, Friend SH, Gentalen E, Giaever G, Hegemann JH, Jones T, Laub M, Liao H, Liebundguth N, Lockhart DJ, Lucau-Danila A, Lussier M, M'Rabet N, Menard P, et al. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 1999, 285(5429):901-906. 10.1126/science.285.5429.901, 10436161.
34. Jo WJ, Loguinov A, Chang M, Wintz H, Nislow C, Arkin AP, Giaever G, Vulpe CD. Identification of genes involved in the toxic response of Saccharomyces cerevisiae against iron and copper overload by parallel analysis of deletion mutants. Toxicol Sci 2008, 101(1):140-151.
35. Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 2002, 30(1):207-210. 10.1093/nar/30.1.207, 99122, 11752295.
36. Huang J, Hu N, Goldstein AM, Emmert-Buck MR, Tang ZZ, Roth MJ, Wang QH, Dawsey SM, Han XY, Ding T, Li G, Giffen C, Taylor PR. High frequency allelic loss on chromosome 17p13.3-p11.1 in esophageal squamous cell carcinomas from a high incidence area in northern China. Carcinogenesis 2000, 21(11):2019-2026. 10.1093/carcin/21.11.2019, 11062163.
37. Schultz DC, Vanderveer L, Berman DB, Hamilton TC, Wong AJ, Godwin AK. Identification of two candidate tumor suppressor genes on chromosome 17p13.3. Cancer Res 1996, 56(9):1997-2002.
38. Maere S, Heymans K, Kuiper M. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 2005, 21(16):3448-3449. 10.1093/bioinformatics/bti551, 15972284.
39. Askwith C, Eide D, Van Ho A, Bernard PS, Li L, Davis-Kaplan S, Sipe DM, Kaplan J. The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake. Cell 1994, 76(2):403-410. 10.1016/0092-8674(94)90346-8, 8293473.
40. Arredondo M, Nunez MT. Iron and copper metabolism. Mol Aspects Med 2005, 26(4-5):313-327.
41. Dancis A, Yuan DS, Haile D, Askwith C, Eide D, Moehle C, Kaplan J, Klausner RD. Molecular characterization of a copper transport protein in S. cerevisiae: an unexpected role for copper in iron transport. Cell 1994, 76(2):393-402. 10.1016/0092-8674(94)90345-X, 8293472.
42. Dancis A, Haile D, Yuan DS, Klausner RD. The Saccharomyces cerevisiae copper transport protein (Ctr1p). Biochemical characterization, regulation by copper, and physiologic role in copper uptake. J Biol Chem 1994, 269(41):25660-25667.
43. Gaxiola RA, Yuan DS, Klausner RD, Fink GR. The yeast CLC chloride channel functions in cation homeostasis. Proc Natl Acad Sci U S A 1998, 95(7):4046-4050. 10.1073/pnas.95.7.4046, 19960, 9520490.
44. Reinders J, Zahedi RP, Pfanner N, Meisinger C, Sickmann A. Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics. J Proteome Res 2006, 5(7):1543-1554. 10.1021/pr050477f, 16823961.
45. Sickmann A, Reinders J, Wagner Y, Joppich C, Zahedi R, Meyer HE, Schonfisch B, Perschil I, Chacinska A, Guiard B, Rehling P, Pfanner N, Meisinger C. The proteome of Saccharomyces cerevisiae mitochondria. Proc Natl Acad Sci U S A 2003, 100(23):13207-13212. 10.1073/pnas.2135385100, 263752, 14576278.
46. Cobine PA, Ojeda LD, Rigby KM, Winge DR. Yeast contain a non-proteinaceous pool of copper in the mitochondrial matrix. J Biol Chem 2004, 279(14):14447-14455. 10.1074/jbc.M312693200, 14729672.
47. Horng YC, Cobine PA, Maxfield AB, Carr HS, Winge DR. Specific copper transfer from the Cox17 metallochaperone to both Sco1 and Cox11 in the assembly of yeast cytochrome C oxidase. J Biol Chem 2004, 279(34):35334-35340. 10.1074/jbc.M404747200, 15199057.
48. Glerum DM, Shtanko A, Tzagoloff A. SCO1 and SCO2 act as high copy suppressors of a mitochondrial copper recruitment defect in Saccharomyces cerevisiae. J Biol Chem 1996, 271(34):20531-20535. 10.1074/jbc.271.34.20531, 8702795.
49. Glerum DM, Shtanko A, Tzagoloff A. Characterization of COX17, a yeast gene involved in copper metabolism and assembly of cytochrome oxidase. J Biol Chem 1996, 271(24):14504-14509. 10.1074/jbc.271.24.14504, 8662933.
50. Klionsky DJ, Herman PK, Emr SD. The fungal vacuole: composition, function, and biogenesis. Microbiol Rev 1990, 54(3):266-292. 372777, 2215422.
51. Li SC, Kane PM. The yeast lysosome-like vacuole: endpoint and crossroads. Biochim Biophys Acta 2009, 1793(4):650-663. 10.1016/j.bbamcr.2008.08.003, 2906225, 18786576.
52. Portnoy ME, Schmidt PJ, Rogers RS, Culotta VC. Metal transporters that contribute copper to metallochaperones in Saccharomyces cerevisiae. Mol Genet Genomics 2001, 265(5):873-882. 10.1007/s004380100482, 11523804.
53. Rees EM, Lee J, Thiele DJ. Mobilization of intracellular copper stores by the ctr2 vacuolar copper transporter. J Biol Chem 2004, 279(52):54221-54229. 10.1074/jbc.M411669200, 15494390.
54. Yuan DS, Dancis A, Klausner RD. Restriction of copper export in Saccharomyces cerevisiae to a late Golgi or post-Golgi compartment in the secretory pathway. J Biol Chem 1997, 272(41):25787-25793. 10.1074/jbc.272.41.25787, 9325307.
55. Bellemare DR, Shaner L, Morano KA, Beaudoin J, Langlois R, Labbe S. Ctr6, a vacuolar membrane copper transporter in Schizosaccharomyces pombe. J Biol Chem 2002, 277(48):46676-46686. 10.1074/jbc.M206444200, 12244050.
56. Bertinato J, Swist E, Plouffe LJ, Brooks SP, L'Abbe MR. Ctr2 is partially localized to the plasma membrane and stimulates copper uptake in COS-7 cells. Biochem J 2008, 409(3):731-740. 10.1042/BJ20071025, 17944601.
57. Qi J, Han A, Yang Z, Li C. Metal-sensing transcription factors Mac1p and Aft1p coordinately regulate vacuolar copper transporter CTR2 in Saccharomyces cerevisiae. Biochem Biophys Res Commun 2012, 423(2):424-428. 10.1016/j.bbrc.2012.05.150, 22683637.
58. Orij R, Urbanus ML, Vizeacoumar FJ, Giaever G, Boone C, Nislow C, Brul S, Smits GJ. Genome-wide analysis of intracellular pH reveals quantitative control of cell division rate by pH(c) in Saccharomyces cerevisiae. Genome Biol 2012, 13(9):R80. 10.1186/gb-2012-13-9-r80, 3506951, 23021432.
59. Brett CL, Kallay L, Hua Z, Green R, Chyou A, Zhang Y, Graham TR, Donowitz M, Rao R. Genome-wide analysis reveals the vacuolar pH-stat of Saccharomyces cerevisiae. PLoS One 2011, 6(3):e17619. 10.1371/journal.pone.0017619, 3056714, 21423800.
60. Serrano R, Bernal D, Simon E, Arino J. Copper and iron are the limiting factors for growth of the yeast Saccharomyces cerevisiae in an alkaline environment. J Biol Chem 2004, 279(19):19698-19704. 10.1074/jbc.M313746200, 14993228.
61. Huss M, Wieczorek H. Inhibitors of V-ATPases: old and new players. J Exp Biol 2009, 212(Pt 3):341-346.
62. Kirchhausen T. Three ways to make a vesicle. Nat Rev Mol Cell Biol 2000, 1(3):187-198. 10.1038/35043117, 11252894.
63. Ishizaki H, Spitzer M, Wildenhain J, Anastasaki C, Zeng Z, Dolma S, Shaw M, Madsen E, Gitlin J, Marais R, Tyers M, Patton EE. Combined zebrafish-yeast chemical-genetic screens reveal gene-copper-nutrition interactions that modulate melanocyte pigmentation. Dis Model Mech 2010, 3(9-10):639-651. 2938393, 20713646.
64. Maglott D, Ostell J, Pruitt KD, Tatusova T. Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res 2011, 39(Database issue):D52-D57. 3013746, 21115458.
65. Kaler SG, Holmes CS, Goldstein DS, Tang J, Godwin SC, Donsante A, Liew CJ, Sato S, Patronas N. Neonatal diagnosis and treatment of Menkes disease. N Engl J Med 2008, 358(6):605-614. 10.1056/NEJMoa070613, 3477514, 18256395.
66. Sasvari Z, Kovalev N, Nagy PD. The GEF1 proton-chloride exchanger affects tombusvirus replication via regulation of copper metabolism in yeast. J Virol 2013, 87(3):1800-1810. 10.1128/JVI.02003-12, 3554144, 23192874.
67. Nagai M, Vo NH, Shin Ogawa L, Chimmanamada D, Inoue T, Chu J, Beaudette-Zlatanova BC, Lu R, Blackman RK, Barsoum J, Koya K, Wada Y. The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Free Radic Biol Med 2012, 52(10):2142-2150. 10.1016/j.freeradbiomed.2012.03.017, 22542443.
68. Cen D, Brayton D, Shahandeh B, Meyskens FL, Farmer PJ. Disulfiram facilitates intracellular Cu uptake and induces apoptosis in human melanoma cells. J Med Chem 2004, 47(27):6914-6920. 10.1021/jm049568z, 15615540.
69. Cen D, Gonzalez RI, Buckmeier JA, Kahlon RS, Tohidian NB, Meyskens FL. Disulfiram induces apoptosis in human melanoma cells: a redox-related process. Mol Cancer Ther 2002, 1(3):197-204.
70. Chen D, Cui QC, Yang H, Dou QP. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res 2006, 66(21):10425-10433. 10.1158/0008-5472.CAN-06-2126, 17079463.
71. Liu P, Brown S, Goktug T, Channathodiyil P, Kannappan V, Hugnot JP, Guichet PO, Bian X, Armesilla AL, Darling JL, Wang W. Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. Br J Cancer 2012, 107(9):1488-1497. 10.1038/bjc.2012.442, 3493777, 23033007.
72. Blackman RK, Cheung-Ong K, Gebbia M, Proia DA, He S, Kepros J, Jonneaux A, Marchetti P, Kluza J, Rao PE, Wada Y, Giaever G, Nislow C. Mitochondrial electron transport is the cellular target of the oncology drug elesclomol. PLoS One 2012, 7(1):e29798. 10.1371/journal.pone.0029798, 3256171, 22253786.
73. Suh JJ, Pettinati HM, Kampman KM, O'Brien CP. The status of disulfiram: a half of a century later. J Clin Psychopharmacol 2006, 26(3):290-302. 10.1097/01.jcp.0000222512.25649.08, 16702894.
74. Deitrich RA, Erwin VG. Mechanism of the inhibition of aldehyde dehydrogenase in vivo by disulfiram and diethyldithiocarbamate. Mol Pharmacol 1971, 7(3):301-307.
75. Johnson RM, Allen C, Melman SD, Waller A, Young SM, Sklar LA, Parra KJ. Identification of inhibitors of vacuolar proton-translocating ATPase pumps in yeast by high-throughput screening flow cytometry. Anal Biochem 2010, 398(2):203-211. 10.1016/j.ab.2009.12.020, 2853757, 20018164.
76. Schlecht U, Miranda M, Suresh S, Davis RW, St Onge RP. Multiplex assay for condition-dependent changes in protein-protein interactions. Proc Natl Acad Sci U S A 2012, 109(23):9213-9218. 10.1073/pnas.1204952109, 3384208, 22615397.
77. Hoon S, Smith AM, Wallace IM, Suresh S, Miranda M, Fung E, Proctor M, Shokat KM, Zhang C, Davis RW, Giaever G, St Onge RP, Nislow C. An integrated platform of genomic assays reveals small-molecule bioactivities. Nat Chem Biol 2008, 4(8):498-506. 10.1038/nchembio.100, 18622389.
78. Smyth GK, Yang YH, Speed T. Statistical issues in cDNA microarray data analysis. Methods Mol Biol 2003, 224:111-136.
79. Smyth GK. Limma: linear models for microarray data. Bioinformatics and Computational Biology Solutions Using R and Bioconductor 2005, 397-420. New York, NY.: Springer, Gentleman R, Carey V, Huber W, Irizarry R, Dudoit S.
80. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society SeriesB 1995, 57:289-300.