Mariner Transposons Contain a Silencer: Possible Role of the Polycomb Repressive Complex 2

PLoS Genetics

Volumn 12, Issue 3, 2016, Pages

  Bire, Solenne ^a,b   Casteret, Sophie ^a   Piégu, Benoît ^a   Beauclair, Linda ^a   Moiré, Nathalie ^c   Arensbuger, Peter ^d   Bigot, Yves ^a  

^a UMR85 PHYSIOLOGIE DE LA REPRODUCTION ET DES COMPORTEMENTS   (France)

^b UNIVERSITY OF LAUSANNE   (Switzerland)

^c UR1282   (France)

^d CALIFORNIA STATE POLYTECHNIC UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GAGA FACTOR; GTGT FACTOR; NEURON RESTRICTIVE SILENCER FACTOR; POLYCOMB REPRESSIVE COMPLEX 2; PROTEIN ALX1; PROTEIN MOS1; PROTEIN NFAT 5; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR YY1; TRANSPOSASE; UNCLASSIFIED DRUG; ALX1 PROTEIN, HUMAN; CHROMATIN; DNA BINDING PROTEIN; HOMEODOMAIN PROTEIN; MARINER TRANSPOSASES; TRANSPOSON;

ANIMAL CELL; ARTICLE; BINDING SITE; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; EPIGENETICS; FLOW CYTOMETRY; GEL ELECTROPHORESIS; GEL MOBILITY SHIFT ASSAY; HELA CELL LINE; HUMAN; HUMAN CELL; HUMAN GENOME; NONHUMAN; OPEN READING FRAME; PLASMID; PROMOTER REGION; PROTEIN EXPRESSION; SILENCER ELEMENT; SOMATIC CELL; TRANSPOSON; ANIMAL; CHROMATIN; GENETICS; GENOME; METABOLISM; PROTEIN MOTIF;

AMINO ACID MOTIFS; ANIMALS; CHROMATIN; DNA TRANSPOSABLE ELEMENTS; DNA-BINDING PROTEINS; GENOME; HELA CELLS; HOMEODOMAIN PROTEINS; HUMANS; NFATC TRANSCRIPTION FACTORS; POLYCOMB REPRESSIVE COMPLEX 2; SILENCER ELEMENTS, TRANSCRIPTIONAL; TRANSPOSASES;

EID: 84962449788     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1005902     Document Type: Article

References (96)

1. de Koning AP, Gu W, Castoe TA, Batzer MA, Pollock DD, . (2011) Repetitive elements may comprise over two-thirds of the human genome. PLoS Genet7: e1002384. doi: 10.1371/journal.pgen.100238422144907
2. Feschotte C, (2008) Transposable elements and the evolution of regulatory networks. Nat Rev Genet9: 397–405. doi: 10.1038/nrg233718368054
3. Bourque G, Leong B, Vega VB, Chen X, Lee YL, et al. (2008) Evolution of the mammalian transcription factor binding repertoire via transposable elements. Genome Res18: 1752–1762. doi: 10.1101/gr.080663.10818682548
4. Emmons SW, Yesner L, (1984) High-frequency excision of transposable element Tc 1 in the nematode Caenorhabditis elegans is limited to somatic cells. Cell36: 599–605. 6321037
5. Coufal NG, Garcia-Perez JL, Peng GE, Yeo GW, Mu Y, et al. (2009) L1 retrotransposition in human neural progenitor cells. Nature460: 1127–1131. doi: 10.1038/nature0824819657334
6. Eickbush MT, Eickbush TH, (2011) Retrotransposition of R2 elements in somatic nuclei during the early development of Drosophila. Mob DNA2: 11. doi: 10.1186/1759-8753-2-1121958913
7. Yamasaki Y, Lim YM, Niwa N, Hayashi S, Tsuda L, (2011) Robust specification of sensory neurons by dual functions of charlatan, a Drosophila NRSF/REST-like repressor of extramacrochaetae and hairy. Genes Cells16: 896–909. doi: 10.1111/j.1365-2443.2011.01537.x21762412
8. Lakowski B, Roelens I, Jacob S, (2006) CoREST-like complexes regulate chromatin modification and neuronal gene expression. J Mol Neurosci29:227–239. 17085781
9. Mortazavi A, Thompson ECL, Garcia ST, Myers RM, Wold B, (2006) Comparative genomics modeling of the NRSF/REST repressor network: from single conserved sites to genome-wide repertoire. Genome Res16: 1208–1221. 16963704
10. Johnson R, Gamblin RJ, Ooi L, Bruce AW, Donaldson IJ, et al. (2006) Identification of the REST regulon reveals extensive transposable element-mediated binding site duplication. Nucl Acids Res34: 3862–3877. 16899447
11. Faunes F, Sanchez N, Moreno M, Olivares GH, Lee-Liu D, et al. (2011) Expression of transposable elements in neural tissues during Xenopus development. PLoS One6: e22569. doi: 10.1371/journal.pone.002256921818339
12. Petrykowska HM, Vockley CM, Elnitski L, (2008) Detection and characterization of silencers and enhancer-blockers in the greater CFTR locus. Genome Res18: 1238–1246. doi: 10.1101/gr.073817.10718436892
13. Sinzelle L, Thuret R, Hwang HY, Herszberg B, Paillard E, et al. (2012) Characterization of a novel Xenopus tropicalis cell line as a model for in vitro studies. Genesis50: 316–324. doi: 10.1002/dvg.2082222083648
14. Demattei MV, Hedhili S, Sinzelle L, Bressac C, Casteret S, et al. (2011) Nuclear importation of Mariner transposases among eukaryotes: motif requirements and homo-protein interactions. PLoS One6: e23693. doi: 10.1371/journal.pone.002369321876763
15. Miskey C, Papp B, Mátés L, Sinzelle L, Keller H, et al. (2007) The ancient mariner sails again: transposition of the human Hsmar1 element by a reconstructed transposase and activities of the SETMAR protein on transposon ends. Mol Cell Biol. 27: 4589–4600. 17403897
16. Wautot V, Khodaei S, Frappart L, Buisson N, Baro E, et al. (2006) Expression analysis of endogenous menin, the product of the multiple endocrine neoplasia type 1 gene, in cell lines and human tissues. Int J Cancer85: 877–881.
17. Sallés FJ, Strickland S, (1999) Analysis of poly(A) tail lengths by PCR: the PAT assay. Methods Mol Biol118: 441–44810549542
18. Murray EL, Schoenberg DR, (2008) Assays for determining poly(A) tail length and the polarity of mRNA decay in mammalian cells. Methods Enzymol448: 483–504. doi: 10.1016/S0076-6879(08)02624-419111191
19. Melo SA, Ropero S, Moutinho C, Aaltonen LA, Yamamoto H, et al. (2009) A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nat Genet41: 365–370. doi: 10.1038/ng.31719219043
20. Liu R, Baillie J, Sissons JG, Sinclair JH, (1994) The transcription factor YY1 binds to negative regulatory elements in the human cytomegalovirus major immediate early enhancer/promoter and mediates repression in non-permissive cells. Nucleic Acids Res22: 2453–2459. 8041605
21. Liu XF, Yan S, Abecassis M, Hummel M, . (2008) Establishment of murine cytomegalovirus latency in vivo is associated with changes in histone modifications and recruitment of transcriptional repressors to the major immediate-early promoter. J Virol82: 10922–10931. doi: 10.1128/JVI.00865-0818753203
22. Liu XF, Yan S, Abecassis M, Hummel M, (2010) Biphasic recruitment of transcriptional repressors to the murine cytomegalovirus major immediate-early promoter during the course of infection in vivo. J Virol84: 3631–3643. doi: 10.1128/JVI.02380-0920106920
23. Bernhard W, Barreto K, Raithatha S, Sadowski I, (2013) An upstream YY1 binding site on the HIV-1 LTR contributes to latent infection. PLoS One8: e77052. doi: 10.1371/journal.pone.007705224116200
24. Matsuda Y, Kobayashi-Ishihara M, Fujikawa D, Ishida T, Watanabe T, et al. (2015) Epigenetic heterogeneity in HIV-1 latency establishment. Sci Rep5: 7701. doi: 10.1038/srep0770125572573
25. Ma SL, Lovmand J, Sørensen AB, Luz A, Schmidt J, et al. (2003) Triple basepair changes within and adjacent to the conserved YY1 motif upstream of the U3 enhancer repeats of SL3-3 murine leukemia virus cause a small but significant shortening of latency of T-lymphoma induction. Virology313: 638–644. 12954229
26. Kao TH, Liao HF, Wolf D, Tai KY, Chuang CY, et al. (2014) Ectopic DNMT3L triggers assembly of a repressive complex for retroviral silencing in somatic cells. J Virol88: 10680–10695. doi: 10.1128/JVI.01176-1424991018
27. Rowe HM, Kapopoulou A, Corsinotti A, Fasching L, Macfarlan TS, et al. (2013) TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells. Genome Res. 23: 452–461. doi: 10.1101/gr.147678.11223233547
28. Schlesinger S, Lee AH, Wang GZ, Green L, Goff SP, (2013) Proviral silencing in embryonic cells is regulated by Yin Yang 1. Cell Rep4: 50–58. doi: 10.1016/j.celrep.2013.06.00323810560
29. Martens JH, O'Sullivan RJ, Braunschweig U, Opravil S, Radolf M, et al. (2005) The profile of repeat-associated histone lysine methylation states in the mouse epigenome. EMBO J24: 800–812. 15678104
30. Casa V, Gabellini D, (2012) A repetitive elements perspective in Polycomb epigenetics. Front Genet. 3: 199–215. doi: 10.3389/fgene.2012.0019923060903
31. Ringrose L, Paro R, (2007) Polycomb/Trithorax response elements and epigenetic memory of cell identity. Development. 134: 223–232. 17185323
32. Kassis JA, Brown JL, (2013) Polycomb group response elements in Drosophila and vertebrates. Adv Genet81: 83–118. doi: 10.1016/B978-0-12-407677-8.00003-823419717
33. Robertson HM, (1993) The mariner transposable element is widespread in insects. Nature362: 241–245. 8384700
34. Otto SJ, McCorkle SR, Hover J, Conaco C, Han JJ, et al. (2007) A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions. J Neurosci27: 6729–6739. 17581960
35. Johnson R, Teh CH, Kunarso G, Wong KY, Srinivasan G, et al. (2008) REST regulates distinct transcriptional networks in embryonic and neural stem cells. PLoS Biol6: e256. doi: 10.1371/journal.pbio.006025618959480
36. Tsuda L, Kaido M, Lim YM, Kato K, Aigaki T, et al. (2006) An NRSF/REST-like repressor downstream of Ebi/SMRTER/Su(H) regulates eye development in Drosophila. EMBO J25: 3191–3202. 16763555
37. Shimojo M, Lee JH, Hersh LB, (2001) Role of zinc finger domains of the transcription factor neuron-restrictive silencer factor/repressor element-1 silencing transcription factor in DNA binding and nuclear localization. J Biol Chem276: 13121–13126. 11145971
38. Tan YP, Li S, Jiang XJ, Loh W, Foo YK, Loh CB, et al. (2010) Regulation of protocadherin gene expression by multiple neuron-restrictive silencer elements scattered in the gene cluster. Nucl Acids Res38: 4985–4997. doi: 10.1093/nar/gkq24620385576
39. Schuettengruber B, Chourrout D, Vervoort M, Leblanc B, Cavalli G, (2007) Genome regulation by polycomb and trithorax proteins. Cell128: 735–745. 17320510
40. Kassis JA, Brown JL, (2013) Polycomb group response elements in Drosophila and vertebrates. Adv Genet81: 83–118. doi: 10.1016/B978-0-12-407677-8.00003-823419717
41. Nestorov P, Tardat M, Peters AH, (2013) H3K9/HP1 and Polycomb: two key epigenetic silencing pathways for gene regulation and embryo development. Curr Top Dev Biol. 104: 243–291. doi: 10.1016/B978-0-12-416027-9.00008-523587244
42. Steffen PA, Ringrose L, (2014) What are memories made of? How Polycomb and Trithorax proteins mediate epigenetic memory. Nat Rev Mol Cell Biol15: 340–356. doi: 10.1038/nrm378924755934
43. Tan J, Yang X, Zhuang L, Jiang X, Chen W, et al. (2007) Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev21: 1050–1063. 17437993
44. Au SL, Wong CC, Lee JM, Wong CM, Ng IO, (2013) EZH2-Mediated H3K27me3 Is Involved in Epigenetic Repression of Deleted in Liver Cancer 1 in Human Cancers. PLoS One8: e68226. 23826380
45. Fujiwara T, Saitoh H, Inoue A, Kobayashi M, Okitsu Y, et al. (2014) 3-Deazaneplanocin A (DZNep), an inhibitor of S-adenosylmethionine-dependent methyltransferase, promotes erythroid differentiation. J Biol Chem289: 8121–8134. doi: 10.1074/jbc.M114.54865124492606
46. Luhui Lin, Yiqun Huang MD, Xudong Ma MD, (2014) Study in the Effect of EZH2 Gene Targeting siRNA on Cell Death in HL-60 Cell Line. Blood124: 5954–5954.
47. Song-Bing H, Hao Z, Jian Z, Guo-Qiang Z, Tuo H, et al. (2015) Inhibition of EZH2 expression is associated with the proliferation, apoptosis and migration of SW620 colorectal cancer cells in vitro. Exp Biol Med240: 546–555.
48. Robertson HM, Zumpano KL, (1997) Molecular evolution of an ancient mariner transposon, Hsmar1, in the human genome. Gene205: 203–217. 9461395
49. Robertson HM, Martos R, (1997) Molecular evolution of the second ancient human mariner transposon, Hsmar2, illustrates patterns of neutral evolution in the human genome lineage. Gene205: 219–228. 9461396
50. Lanzuolo C, Lo Sardo F, Orlando V, (2012) Concerted epigenetic signatures inheritance at PcG targets through replication. Cell Cycle11: 1296–1300. doi: 10.4161/cc.1971022421150
51. Margueron R, Justin N, Ohno K, Sharpe ML, Son J, et al. (2009) Role of the polycomb protein EED in the propagation of repressive histone marks. Nature461: 762–767. doi: 10.1038/nature0839819767730
52. Van Aller GS, Pappalardi MB, Ott HM, Diaz E, Brandt M, et al. (2014) Long residence time inhibition of EZH2 in activated polycomb repressive complex 2. ACS Chem Biol9: 622–629. doi: 10.1021/cb400874824304166
53. Gaydos LJ, Wang W, Strome S, (2014) Gene repression. H3K27me and PRC2 transmit a memory of repression across generations and during development. Science345: 1515–1518. doi: 10.1126/science.125502325237104
54. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, et al. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell125: 315–226. 16630819
55. Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, et al. (2011) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature473: 43–49. doi: 10.1038/nature0990621441907
56. Huda A, Mariño-Ramírez L, Jordan IK, . (2010) Epigenetic histone modifications of human transposable elements: genome defense versus exaptation. Mob DNA1: 2–12. doi: 10.1186/1759-8753-1-220226072
57. Chen T, Dent SY, . (2014) Chromatin modifiers and remodellers: regulators of cellular differentiation. Nat Rev Genet15:93–106. doi: 10.1038/nrg360724366184
58. Keyser P, Borge-Renberg K, Hultmark D, The Drosophila NFAT homolog is involved in salt stress tolerance. Insect Biochem Mol Biol37: 356–362. 17368199
59. López-Rodríguez C, Aramburu J, Jin L, Rakeman AS, Michino M, et al. (2001) Bridging the NFAT and NF-kappaB families: NFAT5 dimerization regulates cytokine gene transcription in response to osmotic stress. Immunity. 15: 47–58. 11485737
60. Hollborn M, Vogler S, Reichenbach A, Wiedemann P, Bringmann A, et al. (2015) Regulation of the hyperosmotic induction of aquaporin 5 and VEGF in retinal pigment epithelial cells: involvement of NFAT5. Mol Vis21: 360–377. 25878490
61. Gordon DF, Wagner J, Atkinson BL, Chiono M, Berry R, et al. (1996) Human Cart-1 Structural organization, chromosomal localization, and functional analysis of a cartilage-specific homeodomain cDNA. DNA Cell Biol15: 531–5418756334
62. Huang Y, Myers SJ, Dingledine R, (1999) Transcriptional repression by REST: recruitment of Sin3A and histone deacetylase to neuronal genes. Nat Neurosci2: 867–872. 10491605
63. Ballas N, Mandel G, (2005) The many faces of REST oversee epigenetic programming of neuronal genes. Curr Opin Neurobiol15: 500–506. 16150588
64. Freeman A, Franciscovich A, Bowers M, Sandstrom DJ, Sanyal S, (2011) NFAT regulates pre-synaptic development and activity-dependent plasticity in Drosophila. Mol Cell Neurosci. 46: 535–547. doi: 10.1016/j.mcn.2010.12.01021185939
65. Mak KM, Lo AC, Lam AK, Yeung PK, Ko BC, et al. (2012) Nuclear factor of activated T cells 5 deficiency increases the severity of neuronal cell death in ischemic injury. Neurosignals20: 237–351. doi: 10.1159/00033189923172129
66. Mishra AK, Tsachaki M, Rister J, Ng J, Celik A, et al. (2013) Binary cell fate decisions and fate transformation in the Drosophila larval eye. PLoS Genet9:e1004027. doi: 10.1371/journal.pgen.100402724385925
67. Dee CT, Szymoniuk CR, Mills PE, Takahashi T, (2013) Defective neural crest migration revealed by a Zebrafish model of Alx1-related frontonasal dysplasia. Hum Mol Genet22: 239–251. doi: 10.1093/hmg/dds42323059813
68. Okamura D, Mochizuki K, Taniguchi H, Tokitake Y, Ikeda M, et al. (2012) REST and its downstream molecule Mek5 regulate survival of primordial germ cells. Dev Biol372: 190–202. doi: 10.1016/j.ydbio.2012.09.01323022299
69. Kok FO, Taibi A, Wanner SJ, Xie X, Moravec CE, et al. (2012) Zebrafish rest regulates developmental gene expression but not neurogenesis. Development139: 3838–48. 22951640
70. Ren X, Kerppola TK, (2011) REST interacts with Cbx proteins and regulates polycomb repressive complex 1 occupancy at RE1 elements. Mol Cell Biol31: 2100–2110. doi: 10.1128/MCB.05088-1121402785
71. Arnold P, Schöler A, Pachkov M, Balwierz PJ, Jørgensen H, et al. (2013) Modeling of epigenome dynamics identifies transcription factors that mediate Polycomb targeting. Genome Res23: 60–73. doi: 10.1101/gr.142661.11222964890
72. Dietrich N, Lerdrup M, Landt E, Agrawal-Singh S, Bak M, et al. (2012) REST-mediated recruitment of polycomb repressor complexes in mammalian cells. PLoS Genet8: e1002494. doi: 10.1371/journal.pgen.100249422396653
73. Jacobson JW, Hartl DL, (1985) Coupled instability of two X-linked genes in Drosophila mauritiana: germinal and somatic mutability. Genetics. 111: 57–65. 3928432
74. Wilson R, Orsetti J, Klocko AD, Aluvihare C, Peckham E, et al. (2003) Post-integration behavior of a Mos1 mariner gene vector in Aedes aegypti. Insect Biochem Mol Biol33: 853–863. 12915177
75. Kahn TG, Schwartz YB, Dellino GI, Pirrotta V, (2006) Polycomb complexes and the propagation of the methylation mark at the Drosophila ubx gene. J Biol Chem281: 29064–29075. 16887811
76. Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, et al. (2007) Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell128: 1089–1103. 17346786
77. Ha H, Song J, Wang S, Kapusta A, Feschotte C, et al. (2014) A comprehensive analysis of piRNAs from adult human testis and their relationship with genes and mobile elements. BMC Genomics15: 545. doi: 10.1186/1471-2164-15-54524981367
78. Bire S, Casteret S, Arnaoty A, Piégu B, Lecomte T, et al. (2013) Transposase concentration controls transposition activity: myth or reality?Gene530: 165–171. doi: 10.1016/j.gene.2013.08.03923994686
79. Bouuaert CC, Tellier M, Chalmers R, (2014) One to rule them all: A highly conserved motif in mariner transposase controls multiple steps of transposition. Mob Genet Elements4: e28807. 24812590
80. Piriyapongsa J, Jordan IK, (2007) A family of human microRNA genes from miniature inverted-repeat transposable elements. PLoS One2: e203. 17301878
81. Sui G, Affar el B, Shi Y, Brignone C, Wall NR, et al. (2004) Yin Yang 1 is a negative regulator of p53. Cell117: 859–872. 15210108
82. Cunningham MD, Brown JL, Kassis JA, (2010) Characterization of the polycomb group response elements of the Drosophila melanogaster invected locus. Mol Cell Biol30: 820–828. doi: 10.1128/MCB.01287-0919948883
83. Feschotte C, (2008) Transposable elements and the evolution of regulatory networks. Nat Rev Genet9: 397–405. doi: 10.1038/nrg233718368054
84. de Souza FS, Franchini LF, Rubinstein M, (2013) Exaptation of transposable elements into novel cis-regulatory elements: is the evidence always strong?Mol Biol Evol30: 1239–1251. doi: 10.1093/molbev/mst04523486611
85. Lowe CB, Bejerano G, Haussler D, (2007) Thousands of human mobile element fragments undergo strong purifying selection near developmental genes. Proc Natl Acad Sci U S A. 104: 8005–8010. 17463089
86. Lindblad-Toh K, Garber M, Zuk O, Lin MF, Parker BJ, et al. (2011)A high-resolution map of human evolutionary constraint using 29 mammals. Nature478: 476–482. doi: 10.1038/nature1053021993624
87. Xie M, Hong C, Zhang B, Lowdon RF, Xing X, et al. (2013) DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape. Nat Genet45: 836–841. doi: 10.1038/ng.264923708189
88. McLean CY, Bristor D, Hiller M, Clarke SL, Schaar BT, Lowe CB, Wenger AM, Bejerano G, (2010) GREAT improves functional interpretation of cis-regulatory regions. Nat Biotechnol28: 495–501. doi: 10.1038/nbt.163020436461
89. Sinzelle L, Jégot G, Brillet B, Rouleux-Bonnin F, Bigot Y, et al. (2008) Factors acting on Mos1 transposition efficiency. BMC Mol Biol9:106. doi: 10.1186/1471-2199-9-10619036139
90. Jung YL, Luquette LJ, Ho JW, Ferrari F, Tolstorukov M, et al. (2014) Impact of sequencing depth in ChIP-seq experiments. Nucleic Acids Res42: e74. doi: 10.1093/nar/gku17824598259
91. Sundaram V, Cheng Y, Ma Z, Li D, Xing X, Edge P, et al. (2014) Widespread contribution of transposable elements to the innovation of gene regulatory networks. Genome Res24: 1963–1976. doi: 10.1101/gr.168872.11325319995
92. Aird D, Ross MG, Chen WS, Danielsson M, Fennell T, et al. (2011) Analyzing and minimizing PCR amplification bias in Illumina sequencing libraries. Genome Biol12:R18. doi: 10.1186/gb-2011-12-2-r1821338519
93. Nakamura K, Oshima T, Morimoto T, Ikeda S, Yoshikawa H, et al. (2011) Sequence-specific error profile of Illumina sequencers. Nucleic Acids Res39:e90. doi: 10.1093/nar/gkr34421576222
94. Ross MG, Russ C, Costello M, Hollinger A, Lennon NJ, et al. (2013) Characterizing and measuring bias in sequence data. Genome Biol14:R51. doi: 10.1186/gb-2013-14-5-r5123718773
95. Olsen CH, (2003) Review of the use of statistics in infection and immunity. Infect Immun71:6689–6692. 14638751
96. Zhao, Xiaobei and Sandelin, Albin. (2014) GMD: Generalized Minimum Distance of distributions. R package. http://CRAN.R-project.org/package=GMD.