The metabolic response of P. putida KT2442 producing high levels of polyhydroxyalkanoate under single- and multiple-nutrient-limited growth: Highlights from a multi-level omics approach

Microbial Cell Factories

Volumn 11, Issue , 2012, Pages

  Poblete Castro, Ignacio ^a,e   Escapa, Isabel F ^b   Jäger, Christian ^c   Puchalka, Jacek ^a   Chi Lam, Carolyn M ^a   Schomburg, Dietmar ^c   Prieto, María A ^b   Martins dos Santos, Vítor A P ^a,d  

^a HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^b CENTRO DE INVESTIGACIONES BIOLÓGICAS   (Spain)

^c TECHNICAL UNIVERSITY OF BRAUNSCHWEIG   (Germany)

^d WAGENINGEN UNIVERSITY   (Netherlands)

^e UNIVERSIDAD TECNOLÓGICA METROPOLITANA   (Chile)

Author keywords

Nutrient limitation; P. putida KT2442; Polyhydroxyalkanoates; Systems biology

Indexed keywords

CARBON; FATTY ACID; HEAT SHOCK PROTEIN; NITROGEN; POLYHYDROXYALKANOIC ACID; TRANSCRIPTOME;

ARTICLE; BACTERIAL GROWTH; BACTERIAL METABOLISM; BACTERIUM CULTURE; CARBON SOURCE; ENERGY METABOLISM; FATTY ACID METABOLISM; GENE EXPRESSION; METABOLOMICS; NONHUMAN; NUTRIENT AVAILABILITY; NUTRIENT LIMITATION; PROTEIN TRANSPORT; PSEUDOMONAS PUTIDA; SYSTEMS BIOLOGY; BIOMASS; BIOSYNTHESIS; GENE EXPRESSION REGULATION; GROWTH, DEVELOPMENT AND AGING; METABOLISM; PROTEOMICS;

BACTERIA (MICROORGANISMS); PSEUDOMONAS PUTIDA;

BIOMASS; CARBON; ENERGY METABOLISM; FATTY ACIDS; GENE EXPRESSION REGULATION, BACTERIAL; METABOLOMICS; NITROGEN; POLYHYDROXYALKANOATES; PROTEOMICS; PSEUDOMONAS PUTIDA; TRANSCRIPTOME;

EID: 84858394287     PISSN: None     EISSN: 14752859     Source Type: Journal    
DOI: 10.1186/1475-2859-11-34     Document Type: Article

References (82)

1. Wilson WA, Roach PJ, Montero M, Baroja-Fernandez E, Munoz FJ, Eydallin G, Viale AM, Pozueta-Romero J. Regulation of glycogen metabolism in yeast and bacteria. FEMS Microbiol Rev 2010, 34(6):952-985. 2927715, 20412306.
2. Nelson KE, Weinel C, Paulsen IT, Dodson RJ, Hilbert H, Martins dos SVAP, Fouts DE, Gill SR, Pop M, Holmes M, et al. Complete genome sequence and comparative analysis of the metabolically versatile Pseudomonas putida KT2440. Environ Microbiol 2002, 4(12):799-808. 10.1046/j.1462-2920.2002.00366.x, 12534463.
3. Timmis KN. Pseudomonas putida: A cosmopolitan opportunist par excellence. Environ Microbiol 2002, 4(12):779-781. 10.1046/j.1462-2920.2002.00365.x, 12534460.
4. Poblete-Castro I, Becker J, Dohnt K, dos Santos V, Wittmann C. Industrial biotechnology of Pseudomonas putida and related species. Appl Microbiol Biotechnol 2012, 93(6):2279-2290. 10.1007/s00253-012-3928-0, 22350258.
5. Kim DY, Hyung WK, Moon GC, Young HR. Biosynthesis, modification, and biodegradation of bacterial medium-chain-length polyhydroxyalkanoates. J Microbiol 2007, 45(2):87-97.
6. Prieto MA, De Eugenio LI, Galan B, Luengo JM, Witholt B. Synthesis and degradation of polyhydroxyalkanoates. Pseudomonas --- A Model in Systems Biology 2007, 5:409-410. Springer, Ramos J-L, Filloux A.
7. Rehm BHA. Bacterial polymers: Biosynthesis, modifications and applications. Nat Rev Microbiol 2010, 8(8):578-592. 10.1038/nrmicro2354, 20581859.
8. Sun Z, Ramsay J, Guay M, Ramsay B. Fed-batch production of unsaturated medium-chain-length polyhydroxyalkanoates with controlled composition by Pseudomonas putida KT2440. Appl Microbiol Biotechnol 2009, 82(4):657-662. 10.1007/s00253-008-1785-7, 19050862.
9. Hartmann R, Hany R, Geiger T, Egli T, Witholt B, Zinn M. Tailored Biosynthesis of Olefinic Medium-Chain-Length Poly[(R)-3-hydroxyalkanoates] in Pseudomonas putida GPo1 with Improved Thermal Properties. Macromol 2004, 37(18):6780-6785.
10. de Eugenio LI, Escapa IF, Morales V, Dinjaski N, Galán B, García JL, Prieto MA. The turnover of medium-chain-length polyhydroxyalkanoates in Pseudomonas putida KT2442 and the fundamental role of PhaZ depolymerase for the metabolic balance. Environ Microbiol 2010, 12(1):207-221. 10.1111/j.1462-2920.2009.02061.x, 19788655.
11. Escapa IF, García JL, Bühler B, Blank LM, Prieto MA. The polyhydroxyalkanoate metabolism controls carbon and energy spillage in Pseudomonas putida. Environmental Microbiology 2012, DOI: 10.1111/j.1462-2920.2011.02684.x.
12. Hoskisson PA, Hobbs G. Continuous culture - Making a comeback?. Microbiology 2005, 151(10):3153-3159. 10.1099/mic.0.27924-0, 16207900.
13. Egli T, Quayle JR. Influence of the carbon: Nitrogen ratio of the growth medium on the cellular composition and the ability of the methylotrophic yeast Hansenula polymorpha to utilize mixed carbon sources. J Gen Microbiol 1986, 132(7):1779-1788.
14. Durner R, Witholt B, Egli T. Accumulation of poly[(R)-3-hydroxyalkanoates] in Pseudomonas oleovorans during growth with octanoate in continuous culture at different dilution rates. Appl Environ Microbiol 2000, 66(8):3408-3414. 10.1128/AEM.66.8.3408-3414.2000, 92163, 10919799.
15. Durner R, Zinn M, Witholt B, Egli T. Accumulation of poly[(R)]-3-hydroxyalkanoates] in Pseudomonas oleovorans during growth in batch and chemostat culture with different carbon sources. Biotechnol Bioeng 2001, 72(3):278-288. 10.1002/1097-0290(20010205)72:3<278::AID-BIT4>3.0.CO;2-G, 11135197.
16. Egli T. On multiple-nutrient-limited growth of microorganisms, with special reference to dual limitation by carbon and nitrogen substrates. Antonie Van Leeuwenhoek 1991, 60(3):225-234. 10.1007/BF00430367, 1687236.
17. Zinn M, Witholt B, Egli T. Dual nutrient limited growth: Models, experimental observations, and applications. J Biotechnol 2004, 113(1-3):263-279. 10.1016/j.jbiotec.2004.03.030, 15380660.
18. Escapa IF, Morales V, Martino VP, Pollet E, Averous L, Garcia JL, Prieto MA. Disruption of B-oxidation pathway in Pseudomonas putida KT2442 to produce new functionalized PHAs with thioester groups. Appl Microbiol Biotechnol 2011, 89(5):1583-1598. 10.1007/s00253-011-3099-4, 21267558.
19. Liu Q, Luo G, Zhou XR, Chen GQ. Biosynthesis of poly(3-hydroxydecanoate) and 3-hydroxydodecanoate dominating polyhydroxyalkanoates by β-oxidation pathway inhibited Pseudomonas putida. Metab Eng 2011, 13(1):11-17. 10.1016/j.ymben.2010.10.004, 20971206.
20. de Eugenio LI, Galan B, Escapa IF, Maestro B, Sanz JM, Garcia JL, Prieto MA. The PhaD regulator controls the simultaneous expression of the pha genes involved in polyhydroxyalkanoate metabolism and turnover in Pseudomonas putida KT2442. Environ Microbiolo 2010, 12(6):1591-1603.
21. Ouyang SP, Luo RC, Chen SS, Liu Q, Chung A, Wu Q, Chen GQ. Production of polyhydroxyalkanoates with high 3-hydroxydodecanoate monomer content by fadB anf fadA knockout mutant of Pseudomonas putida KT2442. Biomacromolecules 2007, 8(8):2504-2511. 10.1021/bm0702307, 17661516.
22. Sohn SB, Kim TY, Park JM, Lee SY. In silico genome-scale metabolic analysis of Pseudomonas putida KT2440 for polyhydroxyalkanoate synthesis, degradation of aromatics and anaerobic survival. Biotechnol J 2010, 5(7):739-750. 10.1002/biot.201000124, 20540110.
23. Puchalka J, Oberhardt MA, Godinho M, Bielecka A, Regenhardt D, Timmis KN, Papin JA, Martins dos Santos VA. Genome-scale reconstruction and analysis of the Pseudomonas putida KT2440 metabolic network facilitates applications in biotechnology. PLoS Comput Biol 2008, 4(10):e1000210. 10.1371/journal.pcbi.1000210, 2563689, 18974823.
24. Nogales J, Palsson BO, Thiele I. A genome-scale metabolic reconstruction of Pseudomonas putida KT2440: iJN746 as a cell factory. BMC Syst Biol 2008, 2:79. 10.1186/1752-0509-2-79, 2569920, 18793442.
25. Huijberts GNM, Eggink G. Production of poly(3-hydroxyalkanoates) by Pseudomonas putida KT2442 in continuous cultures. Appl Microbiol Biotechnol 1996, 46(3):233-239.
26. van Duuren JBJH. Optimization of Pseudomonas putida KT2440 as host for the production of cis, cis-muconate from benzoate 2011, Wageningen: Wageningen.
27. Follonier S, Panke S, Zinn M. A reduction in growth rate of Pseudomonas putida KT2442 counteracts productivity advances in medium-chain-length polyhydroxyalkanoate production from gluconate. Microbial Cell Factories 2011, 10(1):25. 10.1186/1475-2859-10-25, 3107774, 21513516.
28. Huijberts GNM, Eggink G, De Waard P, Huisman GW, Witholt B. Pseudomonas putida KT2442 cultivated on glucose accumulates poly(3- hydroxyalkanoates) consisting of saturated and unsaturated monomers. Appl Environ Microbiol 1992, 58(2):536-544. 195281, 1610179.
29. Kolkman A, Daran-Lapujade P, Fullaondo A, Olsthoorn MMA, Pronk JT, Slijper M, Heck AJR. Proteome analysis of yeast response to various nutrient limitations. Molecular Systems Biology 2006, 2:2006-0026. 1681510, 16788596.
30. Lu P, Vogel C, Wang R, Yao X, Marcotte EM. Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation. Nat Biotech 2007, 25(1):117-124.
31. Verhoef S, Ballerstedt H, Volkers RJM, De Winde JH, Ruijssenaars HJ. Comparative transcriptomics and proteomics of p-hydroxybenzoate producing Pseudomonas putida S12: Novel responses and implications for strain improvement. Appl Microbiolo Biotechnol 2010, 87(2):679-690.
32. Resch A, Leicht S, Saric M, Pásztor L, Jakob A, Götz F, Nordheim A. Comparative proteome analysis of Staphylococcus aureus biofilm and planktonic cells and correlation with transcriptome profiling. Proteomics 2006, 6(6):1867-1877. 10.1002/pmic.200500531, 16470655.
33. Lee MV, Topper SE, Hubler SL, Hose J, Wenger CD, Coon JJ, Gasch AP. A dynamic model of proteome changes reveals new roles for transcript alteration in yeast. Mol Syst Biol 2011, 7:514. 3159980, 21772262.
34. Saito K, Matsuda F. Metabolomics for functional genomics, systems biology, and biotechnology. Annual Review of Plant Biology 2010, 61:463-489. 10.1146/annurev.arplant.043008.092035, 19152489.
35. Martins Dos Santos VAP, Heim S, Moore ERB, Strätz M, Timmis KN. Insights into the genomic basis of niche specificity of Pseudomonas putida KT2440. Environ Microbiol 2004, 6(12):1264-1286. 10.1111/j.1462-2920.2004.00734.x, 15560824.
36. Mobley HLT, Island MD, Hausinger RP. Molecular biology of microbial ureases. Microbiol Rev 1995, 59(3):451-480. 239369, 7565414.
37. Burne RA, Chen YYM. Bacterial ureases in infectious diseases. Microbes and Infection 2000, 2(5):533-542. 10.1016/S1286-4579(00)00312-9, 10865198.
38. Bellido F, Martin NL, Siehnel RJ, Hancock REW. Reevaluation, using intact cells, of the exclusion limit and role of porin OprF in Pseudomonas aeruginosa outer membrane permeability. J Bacteriol 1992, 174(16):5196-5203. 206352, 1322882.
39. Hancock REW, Decad GM, Nikaido H. Identification of the protein producing transmembrane diffusion pores in the outer membranes of Pseudomonas aeruginosa PA01. Biochim Biophys Acta 1979, 554(2):323-331. 10.1016/0005-2736(79)90373-0, 114220.
40. Peng X, Xu C, Ren H, Lin X, Wu L, Wang S. Proteomic analysis of the sarcosine-insoluble outer membrane fraction of Pseudomonas aeruginosa responding to ampicilin, kanamycin, and tetracycline resistance. J Proteome Res 2005, 4(6):2257-2265. 10.1021/pr050159g, 16335974.
41. Trias J, Nikaido H. Protein D2 channel of the Pseudomonas aeruginosa outer membrane has a binding site for basic amino acids and peptides. J Biol Chem 1990, 265(26):15680-15684.
42. Ochs MM, Lu CD, Hancock REW, Abdelal AT. Amino acid-mediated induction of the basic amino acid-specific outer membrane porin OprD from Pseudomonas aeruginosa. J Bacteriol 1999, 181(17):5426-5432. 94052, 10464217.
43. Bell A, Bains M, Hancock REW. Pseudomonas aeruginosa outer membrane protein OprH: Expression from the cloned gene and function in EDTA and gentamicin resistance. J Bacteriol 1991, 173(21):6657-6664. 209012, 1938872.
44. Volkers RJM, De Jong AL, Hulst AG, Van Baar BLM, De Bont JAM, Wery J. Chemostat-based proteomic analysis of toluene-affected Pseudomonas putida S12. Environ Microbiol 2006, 8(9):1674-1679. 10.1111/j.1462-2920.2006.01056.x, 16913927.
45. Steinbüchel A, Lutke-Eversloh T. Metabolic engineering and pathway construction for biotechnological production of relevant polyhydroxyalkanoates in microorganisms. Biochem Eng J 2003, 16(2):81-96.
46. Liu W, Chen GQ. Production and characterization of medium-chain-length polyhydroxyalkanoate with high 3-hydroxytetradecanoate monomer content by fadB and fadA knockout mutant of Pseudomonas putida KT2442. Appl Microbiol Biotechnol 2007, 76(5):1153-1159. 10.1007/s00253-007-1092-8, 17668200.
47. Olivera ER, Carnicero D, Jodra R, Miambres B, Garcia B, Abraham GA, Gallardo A, Roman JS, Garcia JL, Naharro G, et al. Genetically engineered Pseudomonas: A factory of new bioplastics with broad applications. Environ Microbiol 2001, 3(10):612-618. 10.1046/j.1462-2920.2001.00224.x, 11722541.
48. Huisman GW, Wonink E, De Koning G, Preusting H, Witholt B. Synthesis of poly(3-hydroxyalkanoates) by mutant and recombinant Pseudomonas strains. Appl Microbiol Biotechnol 1992, 38(1):1-5.
49. Sun Z, Ramsay JA, Guay M, Ramsay BA. Carbon-limited fed-batch production of medium-chain-length polyhydroxyalkanoates from nonanoic acid by Pseudomonas putida KT2440. Appl Microbiol Biotechnol 2007, 74(1):69-77. 10.1007/s00253-006-0655-4, 17063330.
50. Galan B, Dinjaski N, Maestro B, De Eugenio LI, Escapa IF, Sanz JM, Garcia JL, Prieto MA. Nucleoid-associated PhaF phasin drives intracellular location and segregation of polyhydroxyalkanoate granules in Pseudomonas putida KT2442. Mol Microbiol 2011, 79(2):402-418. 10.1111/j.1365-2958.2010.07450.x, 21219460.
51. Rehm BHA, Krüger N, Steinbüchel A. A new metabolic link between fatty acid de novo synthesis and polyhydroxyalkanoic acid synthesis. The phaG gene from Pseudomonas putida KT2440 encodes a 3-hydroxyacyl-acyl carrier protein-coenzyme a transferase. J Biol Chem 1998, 273(37):24044-24051. 10.1074/jbc.273.37.24044, 9727022.
52. Huijberts GN, de Rijk TC, de Waard P, Eggink G. 13C nuclear magnetic resonance studies of Pseudomonas putida fatty acid metabolic routes involved in poly(3-hydroxyalkanoate) synthesis. J Bacteriol 1994, 176(6):1661-1666. 205252, 8132461.
53. Ren Q, de Roo G, Witholt B, Zinn M, Thony-Meyer L. Influence of growth stage on activities of polyhydroxyalkanoate (PHA) polymerase and PHA depolymerase in Pseudomonas putida U. BMC Microbiol 2010, 10(1):254. 10.1186/1471-2180-10-254, 2959000, 20937103.
54. Ren Q, de Roo G, Ruth K, Witholt B, Zinn M, Thony-Meyer L. Simultaneous Accumulation and Degradation of Polyhydroxyalkanoates: Futile Cycle or Clever Regulation?. Biomacromolecules 2009, 10(4):916-922. 10.1021/bm801431c, 19267463.
55. Garcia B, Olivera ER, Miambres B, Fernandez-Valverde M, Cacedo LM, Prieto MA, Garcia JL, Martinez M, Luengo JM. Novel Biodegradable Aromatic Plastics from a Bacterial Source. J Biol Chem 1999, 274(41):29228-29241. 10.1074/jbc.274.41.29228, 10506180.
56. Ruiz JA, Lopez NI, Fernandez RO, Medez BS. Polyhydroxyalkanoate degradation is associated with nucleotide accumulation and enhances stress resistance and survival of Pseudomonas oleovorans in natural water microcosms. Appl Environ Microbiol 2001, 67(1):225-230. 10.1128/AEM.67.1.225-230.2001, 92552, 11133449.
57. Hervas AB, Canosa I, Santero E. Transcriptome analysis of Pseudomonas putida in response to nitrogen availability. J Bacteriol 2008, 190(1):416-420. 10.1128/JB.01230-07, 2223721, 17965157.
58. Klinke S, Dauner M, Scott G, Kessler B, Witholt B. Inactivation of isocitrate lyase leads to increased production of medium-chain-length poly(3-hydroxyalkanoates) in Pseudomonas putida. Appl Environ Microbiol 2000, 66(3):909-913. 10.1128/AEM.66.3.909-913.2000, 91921, 10698750.
59. Hua Q, Yang C, Oshima T, Mori H, Shimizu K. Analysis of Gene Expression in Escherichia coli in Response to Changes of Growth-Limiting Nutrient in Chemostat Cultures. Appl Environ Microbiol 2004, 70(4):2354-2366. 10.1128/AEM.70.4.2354-2366.2004, 383082, 15066832.
60. Morgunov IG, Solodovnikova NY, Sharyshev AA, Kamzolova SV, Finogenova TV. Regulation of NAD + -Dependent isocitrate dehydrogenase in the citrate producing yeast Yarrowia lipolytica. Biochem Mosc 2004, 69(12):1391-1398.
61. Rojo F. Carbon catabolite repression in Pseudomonas: Optimizing metabolic versatility and interactions with the environment. FEMS Microbiol Rev 2010, 34(5):658-684.
62. Kawakami T, Kuroki M, Ishii M, Igarashi Y, Arai H. Differential expression of multiple terminal oxidases for aerobic respiration in Pseudomonas aeruginosa. Environ Microbiol 2010, 12(6):1399-1412.
63. Morales G, Ugidos A, Rojo F. Inactivation of the Pseudomonas putida cytochrome o ubiquinol oxidase leads to a significant change in the transcriptome and to increased expression of the CIO and cbb3-1 terminal oxidases. Environ Microbiol 2006, 8(10):1764-1774. 10.1111/j.1462-2920.2006.01061.x, 16958757.
64. Dinamarca MA, Aranda-Olmedo I, Puyet A, Rojo F. Expression of the Pseudomonas putida OCT plasmid alkane degradation pathway is modulated by two different global control signals: Evidence from continuous cultures. J Bacteriol 2003, 185(16):4772-4778. 10.1128/JB.185.16.4772-4778.2003, 166476, 12896996.
65. Russell JB, Cook GM. Energetics of bacterial growth: Balance of anabolic and catabolic reactions. Microbiol Rev 1995, 59(1):48-62. 239354, 7708012.
66. Hervas AB, Canosa I, Little R, Dixon R, Santero E. NtrC-dependent regulatory network for nitrogen assimilation in Pseudomonas putida. J Bacteriol 2009, 191(19):6123-6135. 10.1128/JB.00744-09, 2747892, 19648236.
67. Sonawane A, Kloppner U, Hovel S, Volker U, Rohm KH. Identification of Pseudomonas proteins coordinately induced by acidic amino acids and their amides: A two-dimensional electrophoresis study. Microbiology 2003, 149(10):2909-2918. 10.1099/mic.0.26454-0, 14523123.
68. Sonawane A, Klöppner U, Derst C, Röhm KH. Utilization of acidic amino acids and their amides by pseudomonads: Role of periplasmic glutaminase-asparaginase. Arch Microbiol 2003, 179(3):151-159.
69. Zhao YH, Li HM, Qin LF, Wang HH, Chen GQ. Disruption of the polyhydroxyalkanoate synthase gene in Aeromonas hydrophila reduces its survival ability under stress conditions. FEMS Microbiol Lett 2007, 276(1):34-41. 10.1111/j.1574-6968.2007.00904.x, 17888005.
70. Han MJ, Sang Sun Y, Sang Yup L. Proteome analysis of metabolically engineered Escherichia coli producing poly(3-hydroxybutyrate). J Bacteriol 2001, 183(1):301-308. 10.1128/JB.183.1.301-308.2001, 94879, 11114930.
71. Kang Z, Wang Q, Zhang H, Qi Q. Construction of a stress-induced system in Escherichia coli for efficient polyhydroxyalkanoates production. Appl Microbiol Biotechnol 2008, 79(2):203-208. 10.1007/s00253-008-1428-z, 18347791.
72. Tessmer N, König S, Malkus U, Reichelt R, Pötter M, Steinbüchel A. Heat-shock protein HspA mimics the function of phasins sensu stricto in recombinant strains of Escherichia coli accumulating polythioesters or polyhydroxyalkanoates. Microbiology 2007, 153(2):366-374. 10.1099/mic.0.29260-0, 17259608.
73. Caldas TD, El Yaagoubi A, Richarme G. Chaperone properties of bacterial elongation factor EF-Tu. J Biol Chem 1998, 273(19):11478-11482. 10.1074/jbc.273.19.11478, 9565560.
74. Rodnina MV, Savelsbergh A, Katunin VI, Wintermeyer W. Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome. Nature 1997, 385(6611):37-41. 10.1038/385037a0, 8985244.
75. Bagdasarian M, Lurz R, Ruckert B. Specific-purpose plasmid cloning vectors. II. Broad host range, high copy number, RSF 1010-derived vectors, and a host-vector system for gene cloning in Pseudomonas. Gene 1981, 16(1-3):237-247. 10.1016/0378-1119(81)90080-9, 6282695.
76. Lageveen RG, Huisman GW, Preusting H, Ketelaar P, Eggink G, Witholt B. Formation of Polyesters by Pseudomonas oleovorans: Effect of Substrates on Formation and Composition of Poly-(R)-3-Hydroxyalkanoates and Poly-(R)-3-Hydroxyalkenoates. Appl Environ Microbiol 1988, 54(12):2924-2932. 204405, 16347790.
77. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome biology 2004, 5(10):R80. 10.1186/gb-2004-5-10-r80, 545600, 15461798.
78. Kauffmann A, Gentleman R, Huber W. arrayQualityMetrics - A bioconductor package for quality assessment of microarray data. Bioinformatics 2009, 25(3):415-416. 10.1093/bioinformatics/btn647, 2639074, 19106121.
79. Ritchie ME, Silver J, Oshlack A, Holmes M, Diyagama D, Holloway A, Smyth GK. A comparison of background correction methods for two-colour microarrays. Bioinformatics 2007, 23(20):2700-2707. 10.1093/bioinformatics/btm412, 17720982.
80. Huber W, Von Heydebreck A, Sultmann H, Poustka A, Vingron M. Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 2002, 18(SUPPL 1):S96-S104. 10.1093/bioinformatics/18.suppl_1.S96, 12169536.
81. Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology 2004, 3(1):3.
82. Hiller K, Hangebrauk J, Jager C, Spura J, Schreiber K, Schomburg D. Metabolite detector: Comprehensive analysis tool for targeted and nontargeted GC/MS based metabolome analysis. Anal Chem 2009, 81(9):3429-3439. 10.1021/ac802689c, 19358599.