Comparative transcriptome analysis of Gastrodia elata (Orchidaceae) in response to fungus symbiosis to identify gastrodin biosynthesis-related genes

BMC Genomics

Volumn 17, Issue 1, 2016, Pages

  Tsai, Chi Chu ^a,b   Wu, Keh Ming ^c   Chiang, Tzen Yuh ^d   Huang, Chun Yen ^a   Chou, Chang Hung ^e   Li, Shu Ju ^a   Chiang, Yu Chung ^f,g  

^a FISHERIES RESEARCH INSTITUTE   (Taiwan)

^b NATIONAL PINGTUNG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Taiwan)

^c Welgene Biotech Co Ltd   (Taiwan)

^d NATIONAL CHENG KUNG UNIVERSITY   (Taiwan)

^e CHINA MEDICAL UNIVERSITY   (Taiwan)

^f NATIONAL SUN YAT SEN UNIVERSITY   (Taiwan)

^g KAOHSIUNG MEDICAL UNIVERSITY   (Taiwan)

Author keywords

Deep sequencing; Gastrodin; Gene regulation; Glycosyltransferase; Monooxygenase

Indexed keywords

GASTRODIN; TRANSCRIPTOME; BENZYL ALCOHOL DERIVATIVE; GLUCOSIDE; PLANT RNA;

ARMILLARIA; ARMILLARIA MELLEA; ARTICLE; BIOSYNTHESIS; COMPARATIVE STUDY; CONTROLLED STUDY; DOWN REGULATION; FUNGAL GENOME; GASTRODIA ELATA; GENE CONTROL; GENE EXPRESSION; GENE FUNCTION; GENE IDENTIFICATION; GENE MAPPING; GENOME ANALYSIS; GLYCOSYLATION; HYDROXYLATION; MOLECULAR DYNAMICS; NONHUMAN; PLANT GENOME; PLANT PATHOGEN INTERACTION; PLANT RESPONSE; SEQUENCE ANALYSIS; SYMBIOSIS; UPREGULATION; VEGETATIVE PROPAGATION; AGARICALES; GASTRODIA; GENE EXPRESSION REGULATION; GENE ONTOLOGY; GENETICS; HIGH THROUGHPUT SEQUENCING; MICROBIOLOGY; MOLECULAR GENETICS; MYCORRHIZA; PLANT TUBER;

AGARICALES; BENZYL ALCOHOLS; GASTRODIA; GENE EXPRESSION REGULATION, PLANT; GENE ONTOLOGY; GLUCOSIDES; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; MOLECULAR SEQUENCE ANNOTATION; MYCORRHIZAE; PLANT TUBERS; RNA, PLANT; SEQUENCE ANALYSIS, RNA; SYMBIOSIS; TRANSCRIPTOME;

EID: 84960088215     PISSN: None     EISSN: 14712164     Source Type: Journal    
DOI: 10.1186/s12864-016-2508-6     Document Type: Article

References (112)

1. Zhang W, Li B. The biological relationship of Gastrodia elata and Armillaria mellea. Acta Bot Sin. 1980;22:57-62.
2. Huang H, Liang Z, Wang W. Review of nutrient source studies on Gastrodia elata Bl growth up. J Northwest Sci Tech Univ Agric For. 2004;32:145-53.
3. Park E, Lee W, Ahn J. In vitro propagation of myco-heterotrophic Gastrodia elata. Hortic Environ Biotech. 2012;53:415-20.
4. Liu H, Luo Y, Liu H. Studies of mycorrhizal fungi of Chinese orchids and their role in orchid conservation in China-A review. Bot Rev. 2010;76:241-62.
5. Park E, Lee W. In vitro symbiotic germination of myco-heterotrophic Gastrodia elata by Mycena species. Plant Biotech Rep. 2013;7:185-91.
6. Xu J, Gao S. Retrospect on the research of the cultivation of Gastrodia elata Bl, a rare traditional Chinese medicine. Chinese Med J. 2000;113:686-92.
7. Xu J, Ran Y, Mou C, Wang C, Cao J, Wang M, et al. A brief report on the nutritious sources of seed germination of Gastrodia elata. Bull Chin Mat Med. 1981;6:2.
8. Xu J, Ran Y, Guo S. Studies on the life cycle of Gastrodia elata. Acta Acad Med Sin. 1989;11:237-41.
9. Zhou J, Yang Y, Liang H, Liu C. Morphology of Gastrodia elata. Peijin: Science Publish Center; 1987. p. 1-122.
10. Liu T, Li CM, Han YL, Chiang TY, Chiang YC, Sung HM. Highly diversified fungi are associated with the achlorophyllous orchid Gastrodia flavilabella. BMC Genomics. 2015;16:185.
11. Fan L, Guo S. Interaction between protocorms of Gastrodia elata (orchidaceae) and Mycena dendrobii in symbiotic germination. Mycosystema. 1999;18:219-25.
12. Fan L, Guo S, Xiao P. Interaction between protocorms of Gastrodia elata (orchidaceae) and Mycena anoectochila during symbiotic germination. Mycosystema. 2001;20:539-46.
13. Fan L, Guo S, Cao W, Xiao P, Xu J. Isolation, culture, identification and biological activity of Mycena orchidicola sp. nov. inCymbidium sinense (orchidaceae). Acta Mycol Sin. 1996;15:251-5.
14. Guo S, Fan L, Cao W, Xu J, Xiao P. Mycena anoectochila sp. nov. isolated from mycorrhizal roots of Anoectochilus roxburghii from Xishuangbanna, China. Mycologia. 1997;89:952-4.
15. Guo S, Fan L, Cao W, Chen X. Mycena dendrobii, a new mycorrhizal fungus. Mycosystema. 1999;18:141-4.
16. Xu J, Guo X. Fungus associated with nutrition of seed germination of Gastrodia elata-Mycena osmundicola Lange. Acta Mycol Sin. 1989;8:221-6.
17. Guo S, Xu J. Studies on the cell ultrastructure in the course of Gastrodia elata digesting Mycena osmundicola LANGE and Armillaria mellea FR. Acta Mycol Sin. 1990;9:218-25.
18. Kusano S. Gastrodia elata and its symbiotic association with Armillaria mellea. J Coll Agric Imp Univ Tokyo. 1911;4:1-65.
19. Zou N, Bai X, Lu J, Yang J, Xu G, Sun D. Study on symbiotic mechanism between Gastrodia elata Blume and Armillaria mellea in tissue culture system. Med Plant. 2010;1:91-2.
20. Lan J, Xu J, Li J. Studies on the infecting process of labelled Armillaria mellea to Gastrodia elata. Acta Agric Nucleatae Sinica. 1986;10:123-5.
21. Xu J. The changes of cell structure in the courses of Armillaria mellea penetrating the nutritional stems of Gastrodia elata. Acta Acad Med Sin. 2001;23:150-3.
22. Xu J, Fan L. Cytodifferentiation of the seeds (protocorms) and vegetative propagation corms colonized by mycorrhizal fungi. Acta Bot Sin. 2001;43:1003-10.
23. Tang W, Eisenbrand G. Gastrodia elata B1. Chinese drugs of plant origin. Berlin/Heidelberg: Springer-Verlag; 1992. p. 545-8.
24. Bensky D, Gamble A. Chinese herbal medicine: materia medica. Revised Edition. Seattle: Eastland Press; 1993. p. 971-4.
25. Jung T, Suh S, Lee H, Kim I, Kim H, Yoo H, et al. Protective effects of several components of Gastrodia elata on lipid peroxidation in gerbil brain homogenates. Phytother Res. 2007;21:960-4.
26. Kim D, Kim J, Han Y. Alzheimer's disease drug discovery from herbs: neuroprotectivity from β-Amyloid (1-42) insult. J Altern Complement Med. 2007;13:333-40.
27. Feng X, Chen Y, Yang J. Studies on constituents of Tian-Ma.Gastrodia elata Bl. Acta Chim Sin. 1979;37:175-81.
28. Zhou J, Yang Y, Yang J. Chemistry of Gastrodia elata Bl. I. Isolation and identification of chemical constituents of Gastrodia elata Bl. Acta Chim Sin. 1979;37:183-8.
29. Zhao Y, Cao Q, Xiang Y, Hu Z. Identification and determination of active components in Gastrodia elata Bl by capillary electrophoresis. J Chromatogr. 1999;849:277-83.
30. Zhen J. Study on actions of tuber (tian-ma) and vanillin on counteracting epilepsy. Chin J Physiol. 1961;24:187.
31. Huh K, Kim J, Kwon T. The mechanism of anticonvulsive effect of the rhizoma of Gastrodia elata in pentylenetetrazole treated rats. Yakhak Hoechi. 1998;42:330-5.
32. Hsieh C, Tang N, Chiang S, Hsieh C, Lin J. Anticonvulsive and free radical scavenging actions of two herbs, Uncaria rhynchophylla (MIQ) Jack and Gastrodia elata Bl., in kainic acid-treated rats. Life Sci. 1999;65:2071-82.
33. Ha J, Lee D, Lee J, Kim J, Yong C, Kim J, et al. 4-Hydroxybenzaldehyde from Gastrodia elata B1. is active in the antioxidation and GABAergic neuromodulation of the rat brain. J Ethnopharmacol. 2000;73:329-33.
34. Hsieh C, Chang C, Chiang S, Li T, Tang N, Pon C, et al. Anticonvulsive and free radical scavenging activities of vanillyl alcohol in ferric chlorideinduced epileptic seizures in Sprague-awley rats. Life Sci. 2000;67:1185-95.
35. Ha JH, Shin SM, Lee SK, Kim JS, Shin US, Huh K, et al. In vitro effects of hydroxybenzaldehydes from Gastrodia elata and their analogues on GABAergic neurotransmission, and a structure-activity correlation. Planta Med. 2001;67:877-80.
36. Kim H, Moon K, Oh S, Kim S, Lee S. Ether fraction of methanol extracts of Gastrodia elata, a traditional medicinal herb, protects against kainic acid-induced neuronal damage in the mouse hippocampus. Neurosci Lett. 2001;314:65-8.
37. Taguchi H, Yosioka I, Yamasaki K, Kim I. Studies on the constituents of Gastrodia elata Blume. Chem Pharm Bull. 1981;29:55-62.
38. Huang NK, Chern Y, Fang JM, Lin CI, Chen WP, Lin YL. Neuroprotective principles from Gastrodia elata. J Nat Prod. 2007;70:571-4.
39. Yang X, Zhu J, Yang R, Liu J, Li L, Zhang H. Phenolic constituents from the rhizomes of Gastrodia elata. Nat Prod Res. 2007;21:180-6.
40. Gong X, Sucher N. Stroke therapy in traditional medicine (TCM): prospects for drug discovery and development. TiPS. 1999;20:191-6.
41. Jin W, Tian D. Studies on chemisty and pharmacology of Gastrodia elata. Chin Tradit Drug Tech. 2000;2:21-3.
42. Yang S, Lan J, Xu J. Progress of study on Gastrodia elata. Chin Tradit Herb Drugs. 2000;31:6-69.
43. Zhou J, Yang Y, Yang C. Chemical study on gastrodin and related compounds, the synthese of gastrodin and related compounds. Acta Chem Sin. 1980;38:162-5.
44. Ye H, Wang J, Wang S, Tan D. Compare seed stem with commercial rhizoma Gastrodia in pharmacologic effect II. Lishizhen Med Mat Med Res. 2003;14:730-1.
45. Zhu H, Dai P, Zhang W, Chen E, Han W, Chen C, et al. Enzymic synthesis of gastrodin through microbial transformation and purification of gastrodin biosynthesis enzyme. Biol Pharm Bull. 2010;33:1680-4.
46. Peng CX, Gong JS, Zhang XF, Zhang M, Zheng SQ. Production of gastrodin through biotransformation of p-hydroxybenzyl alcohol using hairy root cultures of Datura tatula L. Afr J Biotechnol. 2008;7:211-6.
47. Zhang H, He G, Liu J, Ruan H, Chen Q, Zhang Q, et al. Production of gastrodin through biotransformation of p-2-hydroxybenzyl alcohol by cultured cells of Armillaria luteovirens Sacc. Enzyme Microb Technol. 2008;43:25-30.
48. Sun C, Li Y, Wu Q, Luo H, Sun Y, Song J, et al. De novo sequencing and analysis of the American ginseng root transcriptome using a GS FLX Titanium platform to discover putative genes involved in ginsenoside biosynthesis. BMC Genomics. 2010;11:262.
49. Kouko J, Conn E. The metabolism of aromatic compounds in higher plants: IV. Purification and propertiles of the phenylalanine deaminase of Hordeum vulgare. J Biol Chem. 1961;236:2692-8.
50. Heiden A, Kobel K, Komenda M, Koppmann R, Shao M, Wildt J. Toluene emissions from plants. Geophys Res Lett. 1999;26:1283-6.
51. Singer A, Crowley D, Thompson I. Secondary plant metabolites in phytoremediation and biotransformation. TRENDS Biotech. 2003;21:123-30.
52. Rasi S, Veijanen A, Rintala J. Trace compounds of biogas from different biogas production plants. Energy. 2007;32:1375-80.
53. Zhang H. Research on production of gastrodin through biotransformation by Armillaria luteo-virens Sacc. Master's thesis, Zhejiang University. 2010.
54. Carmona M, Zamarro M, Blazquez B, Durante-Rodriguez G, Juarez J, Valderrama J, et al. Anaerobic catabolism of aromatic compounds: a genetic and genomic view. Microbiol Mol Biol Rev. 2009;73:71-133.
55. Radniecki T, Gilroy C, Semprini L. Linking NE1545 gene expression with cell volume changes in Nitrosomonas europaea cells exposed to aromatic hydrocarbons. Chemosphere. 2011;82:514-20.
56. Jones K, Trudgill P, Hopper D. Metabolism of p-Cresol by the Fungus Aspergillus fumigatus. Microbiology. 1993;59:1125-30.
57. Coon M. Cytochrome P450: nature's most versatile biological catalyst. Annu Rev Pharmacol Toxicol. 2005;45:1-25.
58. Morant M, Bak S, Moller B, Werck-Reichhart D. Plant cytochromes P450: tools for pharmacology, plant protection and phytoremediation. Curr Opin Biotechnol. 2003;14:151-62.
59. Metzker M. Sequencing technologies-the next generation. Nat Rev Genet. 2010;11:31-46.
60. Wakaguri H, Suzuki Y, Katayama T, Kawashima S, Kibukawa E, Hiranuka K, et al. Full-Malaria/Parasites and Full-Arthropods: databases of full-length cDNAs of parasites and arthropods. Nucleic Acids Res. 2009;37:D520-5.
61. Hua W, Zhang Y, Song J, Zhao L, Wang Z. De novo transcriptome sequencing in Salvia miltiorrhiza to identify genes involved in the biosynthesis of active ingredients. Genomics. 2011;98:272-9.
62. Wang W, Wang Y, Zhang Q, Qi Y, Guo D. Global characterization of Artemisia annua glandular trichome transcriptome using 454 pyrosequencing. BMC Genomics. 2009;10:465.
63. Barrero R, Chapman B, Yang Y, Moolhuijzen P, Keeble-Gagnère G, Zhang N, et al. De novo assembly of Euphorbia fischeriana root transcriptome identifies prostratin pathway related genes. BMC Genomics. 2011;12:600.
64. Hao D, Ge G, Xiao P, Zhang Y, Yang L. The first insight into the tissue specific taxus transcriptome via Illumina second generation sequencing. PLoS ONE. 2011;6, e21220.
65. Liu S, Li W, Wu Y, Chen C, Lei J. De novo transcriptome assembly in chili pepper (Capsicum frutescens) to identify genes involved in the biosynthesis of capsaicinoids. PLoS ONE. 2013;8, e48156.
66. Vega-Arreguin J, Ibarra-Laclette E, Jimenez-Moraila B, Martinez O, Vielle-Calzada J, Herrera-Estrella L, et al. Deep sampling of the Palomero maize transcriptome by a high throughput strategy of pyrosequencing. BMC Genomics. 2009;10:299.
67. Annadurai R, Neethiraj R, Jayakumar V, Damodaran A, Rao S, Katta M, et al. De novo transcriptome assembly (NGS) of Curcuma longa L. rhizome reveals novel transcripts related to anticancer and antimalarial terpenoids. PLoS ONE. 2013;8:e56217.
68. Barakat A, DiLoreto D, Zhang Y, Smith C, Baier K, Powell W, et al. Comparison of the transcriptomes of American chestnut (Castanea dentata) and Chinese chestnut (Castanea mollissima) in response to the chestnut blight infection. BMC Plant Biol. 2009;9:51.
69. Mizrachi E, Hefer C, Ranik M, Joubert F, Myburg A. De novo assembled expressed gene catalog of a fast-growing Eucalyptus tree produced by Illumina mRNA-Seq. BMC Genomics. 2010;11:681.
70. Alagna F, D'Agostino N, Torchia L, Servili M, Rao R, Pietrella M, et al. Comparative 454 pyrosequencing of transcripts from two olive genotypes during fruit development. BMC Genomics. 2009;10:399.
71. Shi C, Yang H, Wei C, Yu O, Zhang Z, Jiang C, et al. Deep sequencing of the Camellia sinensis transcriptome revealed candidate genes for major metabolic pathways of tea-specific compounds. BMC Genomics. 2011;12:131.
72. Wang Z, Fang B, Chen J, Zhang X, Luo Z, Huang L, et al. De novo assembly and characterization of root transcriptome using Illumina paired-end sequencing and development of cSSR markers in sweet potato (Ipomoea batatas). BMC Genomics. 2010;11:726.
73. Weber A, Weber K, Carr K, Wilkerson C, Ohlrogge J. Sampling the Arabidopsis transcriptome with massively parallel pyrosequencing. Plant Physiol. 2007;144:32-42.
74. Su C, Chao Y, Chang Y, Chen W, Chen C, Lee A, et al. De novo assembly of expressed transcripts and global analysis of the Phalaenopsis aphrodite transcriptome. Plant Cell Physiol. 2011;52:1501-14.
75. Feng C, Chen M, Xu C, Bai L, Yin X, Li X, et al. Transcriptomic analysis ofChinese bayberry (Myrica rubra) fruit development and ripening using RNA-Seq. BMC Genomics. 2012;13:19.
76. Kudapa H, Bharti A, Cannon S, Farmer A, Mulaosmanovic B, Kramer R, et al. A comprehensive transcriptome assembly of Pigeonpea (Cajanus cajan L.) using sanger and second-generation sequencing platforms. Mol Plant. 2012;5:1020-8.
77. Ranjan A, Ichihashi Y, Farhi M, Zumstein K, Townsley B, David-Schwartz R, et al. De novo assembly and characterization of the transcriptome of the parasitic weed Cuscuta pentagona identifies genes associated with plant parasitism. Plant Physiol. 2014;166:1186-99.
78. Salgado L, Koop D, Pinheiro D, Rivallan R, Guen V, Nicolás M, et al. De novo transcriptome analysis of Hevea brasiliensis tissues by RNA-seq and screening for molecular markers. BMC Genomics. 2014;15:236.
79. Wang Y, Pan Y, Liu Z, Zhu X, Zhai L, Xu L, et al. De novo transcriptome sequencing of radish (Raphanus sativus L.) and analysis of major genes involved in glucosinolate metabolism. BMC Genomics. 2013;14:836.
80. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010;28:511-5.
81. Wang HX, Yang T, Zeng Y, Hu Z. Identification of the gastrodianin gene ga4B in an achlorophyllous plant Gastrodia elata Orchidaceae and its expression pattern during life cycle. Acta Bot Yunnanica. 2007;29:345-50.
82. Hu Z, Yang Z, Wang J. Isolation and partial characterization of an antifungal protein from Gastrodia elata corm. Acta Bot Yunnan. 1988;10:373-80.
83. Shiau Y, Ho W. Method for extraction of gastrodin in Anoectochilus formosanus Hayata. J Taiwan Agric Res. 2012;61:259-68.
84. Bowles D, Lim E, Poppenberger B, Vaistij F. Glycosyltransferases of lipophilic small molecules. Annu Rev Plant Biol. 2006;57:567-97.
85. Gachon C, Langlois-Meurinne M, Saindrenan P. Plant secondary metabolism glycosyltransferases: the emerging functional analysis. Trends Plant Sci. 2005;10:542-9.
86. Lairson L, Henrissat B, Davies G, Withers S. Glycosyltransferases: structures, functions, and mechanisms. Annu Rev Biochem. 2008;77:521-55.
87. Kozak M. Structural features in eukaryotic mRNAs that modulate the initiation of translation. J Biol Chem. 1991;266:19867-70.
88. Morris DR, Geballe AP. Upstream open reading frames as regulators of mRNA translation. Mol Cell Biol. 2000;20:8635-42.
89. Mendell JT, Sharifi NA, Meyers JL, Martinez-Murillo F, Dietz HC. Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat Genet. 2004;36:1073-8.
90. Wittmann J, Hol EM, Jack H-M. hUPF2 silencing identifies physiologic substrates of mammalian nonsense-mediated mRNA decay. Mol Cell Biol. 2006;26:1272-87.
91. Yepiskoposyan H, Aeschimann F, Nilsson D, Okoniewski M, Muhlemann O. Autoregulation of the nonsense-mediated mRNA decay pathway in human cells. RNA. 2011;17:2108-18.
92. Watatani Y, Ichikawa K, Nakanishi N, Fujimoto M, Takeda H, Kimura N, et al. Is regulated by the 5'-untranslated region stress-induced translation of ATF5 mRNA. J Biol Chem. 2008;283:2543-53.
93. Spriggs KA, Bushell M, Willis AE. Translational regulation of gene expression during conditions of cell stress. Mol Cell. 2010;40:228-37.
94. Barbosa C, Romao L. Translation of the human erythropoietin transcript is regulated by an upstream open reading frame in response to hypoxia. RNA. 2014;20:594-608.
95. Zhao C, Datta S, Mandal P, Xu S, Hamilton T. Stress-sensitive regulation of IFRD1 mRNA decay is mediated by an upstream open reading frame. J Biol Chem. 2010;285:8552-62.
96. Hatano M, Umemura M, Kimura N, Yamazaki T, Takeda H, Nakano H, et al. The 5'-untranslated region regulates ATF5 mRNA stability via nonsense-mediated mRNA decay in response to environmental stress. FEBS J. 2013;280:4693-707.
97. Mishra A, Dubey N. Evaluation of some essential oils for their toxicity against fungi causing deterioration of stored food commodities. Appl Environ Microbiol. 1994;60:1101-15.
98. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114-20.
99. Grabherr MG, Haas BJ, Yassour M, Levin JZ, Thompson DA, Amit I, et al. Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat Biotechnol. 2011;29:644-52.
100. Li B, Dewey CN. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics. 2011;12:323.
101. Langmead B, Trapnell C, Pop M, Salzberg S. Ultrafast and memoryefficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10:R25.
102. Robinson MD, Oshlack A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 2010;11:R25.
103. Dillies MA, Rau A, Aubert J, Hennequet-Antier C, Jeanmougin M, Servant N, et al. A comprehensive evaluation of normalization methods for Illumina high-throughput RNA sequencing data analysis. Brief Bioinform. 2013;14:671-83.
104. Edgar R, Domrachev M, Lash AE. Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002;30:207-10.
105. Buchfink B, Xie C, Huson DH. Fast and sensitive protein alignment using DIAMOND. Nat Methods. 2015;12:59-60.
106. Huang H, McGarvey PB, Suzek BE, Mazumder R, Zhang J, Chen Y, et al. A comprehensive protein-centric ID mapping service for molecular data integration. Bioinformatics. 2011;27:1190-1.
107. Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2007;28:27-30.
108. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43, e47.
109. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc B Methodol. 1995;57:289-300.
110. García-Vallejo J, Van het Hof B, Robben J, Van Wijkb J, Van Diea I, Joziasse D, et al. Approach for defining endogenous reference genes in gene expression experiments. Anal Biochem. 2004;329:293-9.
111. Pfaffl M, Tichopad A, Prgomet C, Neuvians T. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper - Excel-based tool using pair-wise correlations. Biotechnol Lett. 2004;26:509-15.
112. -(increment)CT method. Methods. 2001;25:402-8.