Histone modification dynamics at H3K27 are associated with altered transcription of in planta induced genes in Magnaporthe oryzae

Autoři: Wei Zhang aff001;  Jun Huang aff001;  David E. Cook aff001
Působiště autorů: Kansas State University, Department of Plant Pathology, Manhattan, Kansas, United States of America aff001
Vyšlo v časopise: Histone modification dynamics at H3K27 are associated with altered transcription of in planta induced genes in Magnaporthe oryzae. PLoS Genet 17(2): e1009376. doi:10.1371/journal.pgen.1009376
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009376


Transcriptional dynamic in response to environmental and developmental cues are fundamental to biology, yet many mechanistic aspects are poorly understood. One such example is fungal plant pathogens, which use secreted proteins and small molecules, termed effectors, to suppress host immunity and promote colonization. Effectors are highly expressed in planta but remain transcriptionally repressed ex planta, but our mechanistic understanding of these transcriptional dynamics remains limited. We tested the hypothesis that repressive histone modification at H3-Lys27 underlies transcriptional silencing ex planta, and that exchange for an active chemical modification contributes to transcription of in planta induced genes. Using genetics, chromatin immunoprecipitation and sequencing and RNA-sequencing, we determined that H3K27me3 provides significant local transcriptional repression. We detail how regions that lose H3K27me3 gain H3K27ac, and these changes are associated with increased transcription. Importantly, we observed that many in planta induced genes were marked by H3K27me3 during axenic growth, and detail how altered H3K27 modification influences transcription. ChIP-qPCR during in planta growth suggests that H3K27 modifications are generally stable, but can undergo dynamics at specific genomic locations. Our results support the hypothesis that dynamic histone modifications at H3K27 contributes to fungal genome regulation and specifically contributes to regulation of genes important during host infection.

Klíčová slova:

DNA transcription – Fungal genomics – Gene expression – Gene regulation – Genetic loci – Genomic signal processing – Histone modification – Rice


1. Friedman N, Rando OJ. Epigenomics and the structure of the living genome. Genome Res. 2015;25:1482–90. doi: 10.1101/gr.190165.115 26430158

2. Freitag M. Histone Methylation by SET Domain Proteins in Fungi. Annu Rev Microbiol. 2017;71:413–39. doi: 10.1146/annurev-micro-102215-095757 28715960

3. Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 2007;8:286–98. doi: 10.1038/nrg2005 17339880

4. Pfluger J, Wagner D. Histone modifications and dynamic regulation of genome accessibility in plants. Curr Opin Plant Biol. 2007;10:645–52. doi: 10.1016/j.pbi.2007.07.013 17884714

5. Zentner GE, Henikoff S. Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol. 2013;20:259–66. doi: 10.1038/nsmb.2470 23463310

6. Zhang T, Cooper S, Brockdorff N. The interplay of histone modifications—writers that read. EMBO Rep. 2015;16:1467–81. doi: 10.15252/embr.201540945 26474904

7. Klemm SL, Shipony Z, Greenleaf WJ. Chromatin accessibility and the regulatory epigenome. Nat Rev Genet. 2019;20:207–20. doi: 10.1038/s41576-018-0089-8 30675018

8. Rando OJ, Ahmad K. Rules and regulation in the primary structure of chromatin. Curr Opin Cell Biol. 2007;19:250–6. doi: 10.1016/j.ceb.2007.04.006 17466507

9. Hilton IB, D’Ippolito AM, Vockley CM, Thakore PI, Crawford GE, Reddy TE, et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotechnol. 2015;33:510–7. doi: 10.1038/nbt.3199 25849900

10. Connolly LR, Smith KM, Freitag M. The Fusarium graminearum histone H3 K27 methyltransferase KMT6 regulates development and expression of secondary metabolite gene clusters. PLoS Genet. 2013;9:e1003916. doi: 10.1371/journal.pgen.1003916 24204317

11. Seidl MF, Cook DE, Thomma BPHJ. Chromatin Biology Impacts Adaptive Evolution of Filamentous Plant Pathogens. PLoS Pathog. 2016;12:e1005920. doi: 10.1371/journal.ppat.1005920 27812218

12. Suganuma T, Workman JL. Crosstalk among Histone Modifications. Cell. 2008;135:604–7. doi: 10.1016/j.cell.2008.10.036 19013272

13. Tie F, Banerjee R, Stratton CA, Prasad-Sinha J, Stepanik V, Zlobin A, et al. CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development. 2009;136:3131–41. doi: 10.1242/dev.037127 19700617

14. Pasini D, Malatesta M, Jung HR, Walfridsson J, Willer A, Olsson L, et al. Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Res. 2010;38:4958–69. doi: 10.1093/nar/gkq244 20385584

15. Lewis EB. A gene complex controlling segmentation in Drosophila. Nature. 1978;276:565–70. doi: 10.1038/276565a0 103000

16. Schuettengruber B, Bourbon H-M, Di Croce L, Cavalli G. Genome Regulation by Polycomb and Trithorax: 70 Years and Counting. Cell. 2017;171:34–57. doi: 10.1016/j.cell.2017.08.002 28938122

17. Ridenour JB, Möller M, Freitag M. Polycomb Repression without Bristles: Facultative Heterochromatin and Genome Stability in Fungi. Genes (Basel). 2020;11. doi: 10.3390/genes11060638 32527036

18. Jamieson K, Rountree MR, Lewis ZA, Stajich JE, Selker EU. Regional control of histone H3 lysine 27 methylation in Neurospora. Proc Natl Acad Sci U S A. 2013;110:6027–32. doi: 10.1073/pnas.1303750110 23530226

19. Niehaus E-M, Studt L, von Bargen KW, Kummer W, Humpf H-U, Reuter G, et al. Sound of silence: the beauvericin cluster in Fusarium fujikuroi is controlled by cluster-specific and global regulators mediated by H3K27 modification. Environ Microbiol. 2016;18:4282–302. doi: 10.1111/1462-2920.13576 27750383

20. Studt L, Rösler SM, Burkhardt I, Arndt B, Freitag M, Humpf H-U, et al. Knock-down of the methyltransferase Kmt6 relieves H3K27me3 and results in induction of cryptic and otherwise silent secondary metabolite gene clusters in Fusarium fujikuroi. Environ Microbiol. 2016;18:4037–54. doi: 10.1111/1462-2920.13427 27348741

21. Chujo T, Scott B. Histone H3K9 and H3K27 methylation regulates fungal alkaloid biosynthesis in a fungal endophyte-plant symbiosis. Mol Microbiol. 2014;92:413–34. doi: 10.1111/mmi.12567 24571357

22. Lau-Corona D, Bae WK, Hennighausen L, Waxman DJ. Sex-biased genetic programs in liver metabolism and liver fibrosis are controlled by EZH1 and EZH2. PLoS Genet. 2020;16:e1008796. doi: 10.1371/journal.pgen.1008796 32428001

23. Armed PE. Dangerous. Science. 2010;327:804–5. doi: 10.1126/science.327.5967.804 20150482

24. Peng Z, Oliveira-Garcia E, Lin G, Hu Y, Dalby M, Migeon P, et al. Effector gene reshuffling involves dispensable mini-chromosomes in the wheat blast fungus. PLoS Genet. 2019;15:e1008272. doi: 10.1371/journal.pgen.1008272 31513573

25. Inoue Y, Vy TTP, Yoshida K, Asano H, Mitsuoka C, Asuke S, et al. Evolution of the wheat blast fungus through functional losses in a host specificity determinant. Science. 2017;357:80–3. doi: 10.1126/science.aam9654 28684523

26. Zhang H, Zheng X, Zhang Z. The Magnaporthe grisea species complex and plant pathogenesis. Mol Plant Pathol. 2016;17:796–804. doi: 10.1111/mpp.12342 26575082

27. Zhong Z, Norvienyeku J, Chen M, Bao J, Lin L, Chen L, et al. Directional Selection from Host Plants Is a Major Force Driving Host Specificity in Magnaporthe Species. Sci Rep. 2016;6:25591. doi: 10.1038/srep25591 27151494

28. Li G, Zhou X. Xu J-R. Genetic control of infection-related development in Magnaporthe oryzae. Curr Opin Microbiol. 2012;15:678–84. doi: 10.1016/j.mib.2012.09.004 23085322

29. Xu JR. Hamer JE. MAP kinase and cAMP signaling regulate infection structure formation and pathogenic growth in the rice blast fungus Magnaporthe grisea. Genes Dev. 1996;10:2696–706. doi: 10.1101/gad.10.21.2696 8946911

30. Ryder LS, Dagdas YF, Kershaw MJ, Venkataraman C, Madzvamuse A, Yan X, et al. A sensor kinase controls turgor-driven plant infection by the rice blast fungus. Nature. 2019;574:423–7. doi: 10.1038/s41586-019-1637-x 31597961

31. Khang CH, Berruyer R, Giraldo MC, Kankanala P, Park S-Y, Czymmek K, et al. Translocation of Magnaporthe oryzae effectors into rice cells and their subsequent cell-to-cell movement. Plant Cell. 2010;22:1388–403. doi: 10.1105/tpc.109.069666 20435900

32. Oliveira-Garcia E, Valent B. How eukaryotic filamentous pathogens evade plant recognition. Curr Opin Microbiol. 2015;26:92–101. doi: 10.1016/j.mib.2015.06.012 26162502

33. Yi M, Valent B. Communication between filamentous pathogens and plants at the biotrophic interface. Annu Rev Phytopathol. 2013;51:587–611. doi: 10.1146/annurev-phyto-081211-172916 23750888

34. Wu J, Kou Y, Bao J, Li Y, Tang M, Zhu X, et al. Comparative genomics identifies the Magnaporthe oryzae avirulence effector AvrPi9 that triggers Pi9-mediated blast resistance in rice. New Phytol. 2015;206:1463–75. doi: 10.1111/nph.13310 25659573

35. Li W, Wang B, Wu J, Lu G, Hu Y, Zhang X, et al. The Magnaporthe oryzae avirulence gene AvrPiz-t encodes a predicted secreted protein that triggers the immunity in rice mediated by the blast resistance gene Piz-t. Mol Plant-Microbe Interact. 2009;22:411–20. doi: 10.1094/MPMI-22-4-0411 19271956

36. Mosquera G, Giraldo MC, Khang CH, Coughlan S, Valent B. Interaction transcriptome analysis identifies Magnaporthe oryzae BAS1-4 as Biotrophy-associated secreted proteins in rice blast disease. Plant Cell. 2009;21:1273–90. doi: 10.1105/tpc.107.055228 19357089

37. Tanaka S, Schweizer G, Rössel N, Fukada F, Thines M, Kahmann R. Neofunctionalization of the secreted Tin2 effector in the fungal pathogen Ustilago maydis. Nat Microbiol. 2019;4:251–7. doi: 10.1038/s41564-018-0304-6 30510169

38. de Jonge R, van Esse HP, Maruthachalam K, Bolton MD, Santhanam P, Saber MK, et al. Tomato immune receptor Ve1 recognizes effector of multiple fungal pathogens uncovered by genome and RNA sequencing. Proc Natl Acad Sci U S A. 2012;109:5110–5. doi: 10.1073/pnas.1119623109 22416119

39. Pham KTM, Inoue Y, Vu BV, Nguyen HH, Nakayashiki T, Ikeda K-I, et al. MoSET1 (Histone H3K4 Methyltransferase in Magnaporthe oryzae) Regulates Global Gene Expression during Infection-Related Morphogenesis. PLoS Genet. 2015;11:e1005385. doi: 10.1371/journal.pgen.1005385 26230995

40. Bonnet J, Lindeboom RGH, Pokrovsky D, Stricker G, Çelik MH, Rupp RAW, et al. Quantification of Proteins and Histone Marks in Drosophila Embryos Reveals Stoichiometric Relationships Impacting Chromatin Regulation. Dev Cell. 2019;51: 632–644.e6. doi: 10.1016/j.devcel.2019.09.011 31630981

41. Zhang X, Clarenz O, Cokus S, Bernatavichute YV, Pellegrini M, Goodrich J, et al. Whole-genome analysis of histone H3 lysine 27 trimethylation in Arabidopsis. PLoS Biol. 2007;5:e129. doi: 10.1371/journal.pbio.0050129 17439305

42. Schwämmle V, Aspalter C-M, Sidoli S, Jensen ON. Large scale analysis of co-existing post-translational modifications in histone tails reveals global fine structure of cross-talk. Mol Cell Proteomics. 2014;13:1855–65. doi: 10.1074/mcp.O113.036335 24741113

43. Yuan W, Xu M, Huang C, Liu N, Chen S, Zhu B. H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J Biol Chem. 2011;286:7983–9. doi: 10.1074/jbc.M110.194027 21239496

44. Yang H, Howard M, Dean C. Antagonistic roles for H3K36me3 and H3K27me3 in the cold-induced epigenetic switch at Arabidopsis FLC. Curr Biol. 2014;24:1793–7. doi: 10.1016/j.cub.2014.06.047 25065750

45. Zhang S, Liang M, Naqvi NI, Lin C, Qian W, Zhang L-H, et al. Phototrophy and starvation-based induction of autophagy upon removal of Gcn5-catalyzed acetylation of Atg7 in Magnaporthe oryzae. Autophagy. 2017;13:1318–30. doi: 10.1080/15548627.2017.1327103 28594263

46. Liang M, Zhang S, Dong L, Kou Y, Lin C, Dai W, et al. Label-Free Quantitative Proteomics of Lysine Acetylome Identifies Substrates of Gcn5 in Magnaporthe oryzae Autophagy and Epigenetic Regulation. mSystems. 2018;3. doi: 10.1128/mSystems.00270-18 30505942

47. Rösler SM, Kramer K, Finkemeier I, Humpf H-U, Tudzynski B. The SAGA complex in the rice pathogen Fusarium fujikuroi: structure and functional characterization. Mol Microbiol. 2016;102:951–74. doi: 10.1111/mmi.13528 27642009

48. Shimizu M, Nakano Y, Hirabuchi A, Yoshino K, Kobayashi M, Yamamoto K, et al. RNA-Seq of in planta-expressed Magnaporthe oryzae genes identifies MoSVP as a highly expressed gene required for pathogenicity at the initial stage of infection. Mol Plant Pathol. 2019;20:1682–95. doi: 10.1111/mpp.12869 31560822

49. Dong Y, Li Y, Zhao M, Jing M, Liu X, Liu M, et al. Global genome and transcriptome analyses of Magnaporthe oryzae epidemic isolate 98–06 uncover novel effectors and pathogenicity-related genes, revealing gene gain and lose dynamics in genome evolution. PLoS Pathog. 2015;11:e1004801. doi: 10.1371/journal.ppat.1004801 25837042

50. Mentlak TA, Kombrink A, Shinya T, Ryder LS, Otomo I, Saitoh H, et al. Effector-mediated suppression of chitin-triggered immunity by magnaporthe oryzae is necessary for rice blast disease. Plant Cell. 2012;24:322–35. doi: 10.1105/tpc.111.092957 22267486

51. Fernandez J, Orth K. Rise of a Cereal Killer: The Biology of Magnaporthe oryzae Biotrophic Growth. Trends Microbiol. 2018;26:582–97. doi: 10.1016/j.tim.2017.12.007 29395728

52. Sperschneider J, Dodds PN, Gardiner DM, Singh KB, Taylor JM. Improved prediction of fungal effector proteins from secretomes with EffectorP 2.0 Mol Plant Pathol. 2018;19:2094–110. doi: 10.1111/mpp.12682 29569316

53. Böhnert HU, Fudal I, Dioh W, Tharreau D, Notteghem J-L, Lebrun M-H. A putative polyketide synthase/peptide synthetase from Magnaporthe grisea signals pathogen attack to resistant rice. Plant Cell. 2004;16:2499–513. doi: 10.1105/tpc.104.022715 15319478

54. Ray S, Singh PK, Gupta DK, Mahato AK, Sarkar C, Rathour R, et al. Analysis of Magnaporthe oryzae Genome Reveals a Fungal Effector, Which Is Able to Induce Resistance Response in Transgenic Rice Line Containing Resistance Gene. Pi54 Front Plant Sci. 2016;7:1140. doi: 10.3389/fpls.2016.01140 27551285

55. Irieda H, Inoue Y, Mori M, Yamada K, Oshikawa Y, Saitoh H, et al. Conserved fungal effector suppresses PAMP-triggered immunity by targeting plant immune kinases. Proc Natl Acad Sci U S A. 2019;116:496–505. doi: 10.1073/pnas.1807297116 30584105

56. Saitoh H, Fujisawa S, Mitsuoka C, Ito A, Hirabuchi A, Ikeda K, et al. Large-scale gene disruption in Magnaporthe oryzae identifies MC69, a secreted protein required for infection by monocot and dicot fungal pathogens. PLoS Pathog. 2012;8:e1002711. doi: 10.1371/journal.ppat.1002711 22589729

57. Zhong Z, Chen M, Lin L, Han Y, Bao J, Tang W, et al. Population genomic analysis of the rice blast fungus reveals specific events associated with expansion of three main clades. ISME J. 2018;12:1867–78. doi: 10.1038/s41396-018-0100-6 29568114

58. Guo X, Zhong D, Xie W, He Y, Zheng Y, Lin Y, et al. Functional Identification of Novel Cell Death-inducing Effector Proteins from Magnaporthe oryzae. Rice (N Y). 2019 12: 59. doi: 10.1186/s12284-019-0312-z 31388773

59. Chen S, Songkumarn P, Venu RC, Gowda M, Bellizzi M, Hu J, et al. Identification and characterization of in planta-expressed secreted effector proteins from Magnaporthe oryzae that induce cell death in rice. Mol Plant-Microbe Interact. 2013;26:191–202. doi: 10.1094/MPMI-05-12-0117-R 23035914

60. Wang Y, Wu J, Kim SG, Tsuda K, Gupta R, Park S-Y, et al. Magnaporthe oryzae-Secreted Protein MSP1 Induces Cell Death and Elicits Defense Responses in Rice. Mol Plant-Microbe Interact. 2016;29:299–312. doi: 10.1094/MPMI-12-15-0266-R 26780420

61. Collemare J, Seidl MF. Chromatin-dependent regulation of secondary metabolite biosynthesis in fungi: is the picture complete? FEMS Microbiol Rev. 2019;43:591–607. doi: 10.1093/femsre/fuz018 31301226

62. Woloshuk CP, Shim W-B. Aflatoxins, fumonisins, and trichothecenes: a convergence of knowledge. FEMS Microbiol Rev. 2013;37:94–109. doi: 10.1111/1574-6976.12009 23078349

63. Bicocca VT, Ormsby T, Adhvaryu KK, Honda S, Selker EU. ASH1-catalyzed H3K36 methylation drives gene repression and marks H3K27me2/3-competent chromatin. Workman JL, Struhl K, editors. eLife. 2018;7: e41497. doi: 10.7554/eLife.41497 30468429

64. Janevska S, Baumann L, Sieber CMK, Münsterkötter M, Ulrich J, Kämper J, et al. Elucidation of the Two H3K36me3 Histone Methyltransferases Set2 and Ash1 in Fusarium fujikuroi Unravels Their Different Chromosomal Targets and a Major Impact of Ash1 on Genome Stability. Genetics. 2018;208:153–71. doi: 10.1534/genetics.117.1119 29146582

65. Cao Z, Yin Y, Sun X, Han J, Sun QP, Lu M, et al. An Ash1-Like Protein MoKMT2H Null Mutant Is Delayed for Conidium Germination and Pathogenesis in Magnaporthe oryzae. Biomed Res Int. 2016;2016:1575430. doi: 10.1155/2016/1575430 27747223

66. Chen J, Zheng W, Zheng S, Zhang D, Sang W, Chen X, et al. Rac1 is required for pathogenicity and Chm1-dependent conidiogenesis in rice fungal pathogen Magnaporthe grisea. PLoS Pathog. 2008;4:e1000202. doi: 10.1371/journal.ppat.1000202 19008945

67. Khang CH, Park S-Y, Rho H-S, Lee Y-H, Kang S. Filamentous Fungi (Magnaporthe grisea and Fusarium oxysporum). Methods Mol Biol. 2006;344:403–20. doi: 10.1385/1-59745-131-2:403 17033082

68. Valent B, Farrall L, Chumley FG. Magnaporthe grisea genes for pathogenicity and virulence identified through a series of backcrosses. Genetics. 1991;127:87–101. 2016048

69. Sasaki T, Lynch KL, Mueller CV, Friedman S, Freitag M, Lewis ZA. Heterochromatin controls γH2A localization in Neurospora crassa. Eukaryot Cell. 2014;13:990–1000. doi: 10.1128/EC.00117-14 24879124

70. Kumar R, Ichihashi Y, Kimura S, Chitwood DH, Headland LR, Peng J, et al. A High-Throughput Method for Illumina RNA-Seq Library Preparation. Front Plant Sci. 2012;3:202. doi: 10.3389/fpls.2012.00202 22973283

71. Zhang W, Corwin JA, Copeland D, Feusier J, Eshbaugh R, Chen F, et al. Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem. Plant Cell. 2017;29:2727–52. doi: 10.1105/tpc.17.00348 29042403

72. Zhang W, Corwin JA, Copeland DH, Feusier J, Eshbaugh R, Cook DE, et al. Plant-necrotroph co-transcriptome networks illuminate a metabolic battlefield. elife. 2019;8. doi: 10.7554/eLife.44279 31081752

73. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60. doi: 10.1093/bioinformatics/btp324 19451168

74. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21. doi: 10.1093/bioinformatics/bts635 23104886

75. Bao J, Chen M, Zhong Z, Tang W, Lin L, Zhang X, et al. PacBio Sequencing Reveals Transposable Elements as a Key Contributor to Genomic Plasticity and Virulence Variation in Magnaporthe oryzae. Mol Plant. 2017;10:1465–8. doi: 10.1016/j.molp.2017.08.008 28838703

76. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008;9:R137. doi: 10.1186/gb-2008-9-9-r137 18798982

77. Ramírez F, Dündar F, Diehl S, Grüning BA, Manke T. deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 2014;42:W187–91. doi: 10.1093/nar/gku365 24799436

78. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550. doi: 10.1186/s13059-014-0550-8 25516281

79. Götz S, García-Gómez JM, Terol J, Williams TD, Nagaraj SH, Nueda MJ, et al. High-throughput functional annotation and data mining with the Blast2GO suite. Nucleic Acids Res. 2008;36:3420–35. doi: 10.1093/nar/gkn176 18445632

80. Kanehisa M, Goto SKEGG. kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28:27–30. doi: 10.1093/nar/28.1.27 10592173

81. Chen C, Chen H, Zhang Y, Thomas HR, Frank MH, He Y, et al. TBtools: An Integrative Toolkit Developed for Interactive Analyses of Big Biological Data. Mol Plant. 2020;13:1194–202. doi: 10.1016/j.molp.2020.06.009 32585190

82. Venables WN, Ripley BD. Modern Applied Statistics with S. Fourth. New York: Springer; 2002. https://www.stats.ox.ac.uk/pub/MASS4/.

83. Felipe de Mendiburu, Muhammad Yaseen. agricolae: Statistical Procedures for Agricultural Research. 2020.

84. Wickham H. ggplot2: Elegant Graphics for Data Analysis. Springer-Verlag New York; 2016. https://ggplot2.tidyverse.org.

85. Hahne F, Ivanek R. Visualizing Genomic Data Using Gviz and Bioconductor. Methods Mol Biol. 2016;1418:335–51. doi: 10.1007/978-1-4939-3578-9_16 27008022

86. Zhao S, Guo Y, Sheng Q, Shyr Y. Advanced heat map and clustering analysis using heatmap3. Biomed Res Int. 2014;2014:986048. doi: 10.1155/2014/986048 25143956

Článek vyšel v časopise

PLOS Genetics

2021 Číslo 2
Nejčtenější tento týden
Nejčtenější v tomto čísle

Zvyšte si kvalifikaci online z pohodlí domova

Důležitost adherence při depresivním onemocnění
nový kurz
Autoři: MUDr. Eliška Bartečková, Ph.D.

Koncepce osteologické péče pro gynekology a praktické lékaře
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková, Ph.D.

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Všechny kurzy
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se