Chapter 41 : New Virus Discovery in the 21st Century

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The development of new technologies has propelled virus discovery efforts forward at an unprecedented pace. As this area of research has become increasingly active, a review of virus discovery efforts over the last ~10 years is warranted. This chapter describes the evolution of sequence-independent PCR methods, panviral microarrays, and mass sequencing in the discovery of novel viruses. It also highlights the viruses discovered by these methods, and the importance and novelties of some of these viruses. Sequence-independent PCR strategies and new technologies such as microarrays and mass sequencing, while not without their own limitations, circumvent many of the limitations associated with traditional virus discovery methods and consequently have revolutionized the process of virus discovery. The discovery in 2001 of a novel human pneumovirus, called human metapneumovirus (HMPV), relied upon a sequence-independent PCR approach in conjunction with viral culture to identify a previously unknown virus. The first application of virus discovery based on cDNA-amplified fragment length polymorphism (VIDISCA) to virus discovery resulted in the identification of HCoV-NL63. DNA microarrays first emerged in the mid-1990s as powerful tools to measure gene expression or genomic content changes in various organisms. Dideoxy sequencing or Sanger sequencing, first described in 1977, has been the dominant DNA sequencing technology used during the last ~30 years. With the advent of new technologies, a shift has occurred such that in many instances, the rate-limiting step is no longer discovery but understanding the biological relevance and impact of newly discovered viruses.

Citation: Finkbeiner S, Wang D. 2011. New Virus Discovery in the 21st Century, p 641-652. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch41
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Summary of molecular approaches to virus discovery and their first applications.

Citation: Finkbeiner S, Wang D. 2011. New Virus Discovery in the 21st Century, p 641-652. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch41
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Image of FIGURE 2

Schematic of mass sequencing strategies for detection of known and novel viruses.

Citation: Finkbeiner S, Wang D. 2011. New Virus Discovery in the 21st Century, p 641-652. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch41
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1. Abed, Y.,, and G. Boivin. 2008. New Saffold cardioviruses in 3 children, Canada. Emerg. Infect. Dis. 14: 834836.
2. Abed, Y.,, D. Wang, and, G. Boivin. 2007. WU polyomavirus in children, Canada. Emerg. Infect. Dis. 13: 19391941.
3. Allander, T.,, K. Andreasson,, S. Gupta,, A. Bjerkner,, G. Bogdanovic,, M. A. Persson,, T. Dalianis,, T. Ramqvist, and, B. Andersson. 2007. Identification of a third human polyomavirus. J. Virol. 81: 41304136.
4. Allander, T.,, X. de Lamballerie, and, P. Simmonds. 2008. A new arenavirus in transplantation. N. Engl. J. Med. 358: 2638; author reply 26382639.
5. Allander, T.,, S. U. Emerson,, R. E. Engle,, R. H. Purcell, and, J. Bukh. 2001. A virus discovery method incorporating DNase treatment and its application to the identification of two bovine parvovirus species. Proc. Natl. Acad. Sci. USA 98: 1160911614.
6. Allander, T.,, M. T. Tammi,, M. Eriksson,, A. Bjerkner,, A. Tiveljung-Lindell, and, B. Andersson. 2005. Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc. Natl. Acad. Sci. USA 102: 1289112896.
7. Becker, J. C.,, R. Houben,, S. Ugurel,, U. Trefzer,, C. Pföhler, and, D. Schrama. 2009. MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J. Invest. Dermatol. 129: 248250.
8. Bialasiewicz, S.,, D. M. Whiley,, S. B. Lambert,, K. Jacob,, C. Bletchly,, D. Wang,, M. D. Nissen, and, T. P. Sloots. 2008. Presence of the newly discovered human polyomaviruses KI and WU in Australian patients with acute respiratory tract infection. J. Clin. Virol. 41: 6368.
9. Breitbart, M.,, I. Hewson,, B. Felts,, J. M. Mahaffy,, J. Nulton,, P. Salamon, and, F. Rohwer. 2003. Metagenomic analyses of an uncultured viral community from human feces. J. Bacteriol. 185: 62206223.
10. Carpten, J.,, N. Nupponen,, S. Isaacs,, R. Sood,, C. Robbins,, J. Xu,, M. Faruque,, T. Moses,, C. Ewing,, E. Gillanders,, P. Hu,, P. Bujnovszky,, I. Makalowska,, A. Baffoe-Bonnie,, D. Faith,, J. Smith,, D. Stephan,, K. Wiley,, M. Brownstein,, D. Gildea,, B. Kelly,, R. Jenkins,, G. Hostetter,, M. Matikainen,, J. Schleutker,, K. Klinger,, T. Connors,, Y. Xiang,, Z. Wang,, A. De Marzo,, N. Papadopoulos,, O. P. Kallioniemi,, R. Burk,, D. Meyers,, H. Grönberg,, P. Meltzer,, R. Silverman,, J. Bailey-Wilson,, P. Walsh,, W. Isaacs, and, J. Trent. 2002. Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat. Genet. 30: 181184.
11. Carter, B. S.,, G. S. Bova,, T. H. Beaty,, G. D. Steinberg,, B. Childs,, W. B. Isaacs, and, P. C. Walsh. 1993. Hereditary prostate cancer: epidemiologic and clinical features. J. Urol. 150: 797802.
12. Casey, G.,, P. J. Neville,, S. J. Plummer,, Y. Xiang,, L. M. Krumroy,, E. A. Klein,, W. J. Catalona,, N. Nupponen,, J. D. Carpten,, J. M. Trent,, R. H. Silverman, and, J. S. Witte. 2002. RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases. Nat. Genet. 32: 581583.
13. Chang, Y.,, E. Cesarman,, M. S. Pessin,, F. Lee,, J. Culpepper,, D. M. Knowles, and, P. S. Moore. 1994. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266: 18651869.
14. Chiu, C. Y.,, A. A. Alizadeh,, S. Rouskin,, J. D. Merker,, E. Yeh,, S. Yagi,, D. Schnurr,, B. K. Patterson,, D. Ganem, and, J. L. DeRisi. 2007. Diagnosis of a critical respiratory illness caused by human metapneumovirus by use of a panvirus microarray. J. Clin. Microbiol. 45: 23402343.
15. Chiu, C. Y.,, A. L. Greninger,, K. Kanada,, T. Kwok,, K. F. Fischer,, C. Runckel,, J. K. Louie,, C. A. Glaser,, S. Yagi,, D. P. Schnurr,, T. D. Haggerty,, J. Parsonnet,, D. Ganem, and, J. L. DeRisi. 2008. Identification of cardioviruses related to Theiler’s murine encephalomyelitis virus in human infections. Proc. Natl. Acad. Sci. USA 105: 1412414129.
16. Chiu, C. Y.,, A. Urisman,, T. L. Greenhow,, S. Rouskin,, S. Yagi,, D. Schnurr,, C. Wright,, W. L. Drew,, D. Wang,, P. S. Weintrub,, J. L. DeRisi, and, D. Ganem. 2008. Utility of DNA microarrays for detection of viruses in acute respiratory tract infections in children. J. Pediatr. 153: 7683.
17. Choo, Q. L.,, G. Kuo,, A. J. Weiner,, L. R. Overby,, D. W. Bradley, and, M. Houghton. 1989. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359362.
18. Chua, K. B.,, G. Crameri,, A. Hyatt,, M. Yu,, M. R. Tompang,, J. Rosli,, J. McEachern,, S. Crameri,, V. Kumarasamy,, B. T. Eaton, and, L. F. Wang. 2007. A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans. Proc. Natl. Acad. Sci. USA 104: 1142411429.
19. Delgado, S.,, B. R. Erickson,, R. Agudo,, P. J. Blair,, E. Vallejo,, C. G. Albarino,, J. Vargas,, J. A. Comer,, P. E. Rollin,, T. G. Ksiazek,, J. G. Olson, and, S. T. Nichol. 2008. Chapare virus, a newly discovered arenavirus isolated from a fatal hemorrhagic fever case in Bolivia. PLoS Pathog. 4: e1000047.
20. de Souza Luna, L. K.,, S. Baumgarte,, K. Grywna,, M. Panning,, J. F. Drexler, and, C. Drosten. 2008. Identification of a contemporary human parechovirus type 1 by VIDISCA and characterisation of its full genome. Virol. J. 5: 26.
21. Dong, B.,, S. Kim,, S. Hong,, J. Das Gupta,, K. Malathi,, E. A. Klein,, D. Ganem,, J. L. DeRisi,, S. A. Chow, and, R. H. Silverman. 2007. An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors. Proc. Natl. Acad. Sci. USA 104: 16551660.
22. Drexler, J. F.,, L. K. de Souza Luna,, A. Stöcker,, P. S. Almeida,, T. C. Ribeiro,, N. Petersen,, P. Herzog,, C. Pedroso,, H. I. Huppertz,, H. da Costa Ribeiro, Jr.,, S. Baumgarte, and, C. Drosten. 2008. Circulation of 3 lineages of a novel Saffold cardiovirus in humans. Emerg. Infect. Dis. 14: 13981405.
23. Drosten, C.,, S. Gunther,, W. Preiser,, S. van der Werf,, H. R. Brodt,, S. Becker,, H. Rabenau,, M. Panning,, L. Kolesnikova,, R. A. Fouchier,, A. Berger,, A. M. Burguiere,, J. Cinatl,, M. Eickmann,, N. Escriou,, K. Grywna,, S. Kramme,, J. C. Manuguerra,, S. Muller,, V. Rickerts,, M. Sturmer,, S. Vieth,, H. D. Klenk,, A. D. Osterhaus,, H. Schmitz, and, H. W. Doerr. 2003. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 348: 19671976.
24. Feng, H.,, M. Shuda,, Y. Chang, and, P. S. Moore. 2008. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319: 10961100.
25. Finkbeiner, S. R.,, A. F. Allred,, P. I. Tarr,, E. J. Klein,, C. D. Kirkwood, and, D. Wang. 2008. Metagenomic analysis of human diarrhea: viral detection and discovery. PLoS Pathog. 4: e1000011.
26. Fodor, S. P.,, J. L. Read,, M. C. Pirrung,, L. Stryer,, A. T. Lu, and, D. Solas. 1991. Light-directed, spatially addressable parallel chemical synthesis. Science 251: 767773.
27. Foulongne, V.,, N. Kluger,, O. Dereure,, N. Brieu,, B. Guillot, and, M. Segondy. 2008. Merkel cell polyomavirus and Merkel cell carcinoma, France. Emerg. Infect. Dis. 14: 14911493.
28. Garneski, K. M.,, A. H. Warcola,, Q. Feng,, N. B. Kiviat,, J. H. Leonard, and, P. Nghiem. 2009. Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J. Invest. Dermatol. 129: 246248.
29. Gaynor, A. M.,, M. D. Nissen,, D. M. Whiley,, I. M. Mackay,, S. B. Lambert,, G. Wu,, D. C. Brennan,, G. A. Storch,, T. P. Sloots, and, D. Wang. 2007. Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS Pathog. 3: e64.
30. Goessling, W.,, P. H. McKee, and, R. J. Mayer. 2002. Merkel cell carcinoma. J. Clin. Oncol. 20: 588598.
31. Han, T. H.,, J. Y. Chung,, J. W. Koo,, S. W. Kim, and, E. S. Hwang. 2007. WU polyomavirus in children with acute lower respiratory tract infections, South Korea. Emerg. Infect. Dis. 13: 17661768.
32. Jabado, O. J.,, G. Palacios,, V. Kapoor,, J. Hui,, N. Renwick,, J. Zhai,, T. Briese, and, W. I. Lipkin. 2006. Greene SCPrimer: a rapid comprehensive tool for designing degenerate primers from multiple sequence alignments. Nucleic Acids Res. 34: 66056611.
33. Jones, M. S.,, II, B. Harrach,, R. D. Ganac,, M. M. Gozum,, W. P. dela Cruz,, B. Riedel,, C. Pan,, E. L. Delwart, and, D. P. Schnurr. 2007. New adenovirus species found in a patient presenting with gastroenteritis. J. Virol. 81: 59785984.
34. Jones, M. S.,, A. Kapoor,, V. V. Lukashov,, P. Simmonds,, F. Hecht, and, E. Delwart. 2005. New DNA viruses identified in patients with acute viral infection syndrome. J. Virol. 79: 82308236.
35. Jones, M. S.,, V. V. Lukashov,, R. D. Ganac, and, D. P. Schnurr. 2007. Discovery of a novel human picornavirus in a stool sample from a pediatric patient presenting with fever of unknown origin. J. Clin. Microbiol. 45: 21442150.
36. Kapoor, A.,, J. Victoria,, P. Simmonds,, C. Wang,, R. W. Shafer,, R. Nims,, O. Nielsen, and, E. Delwart. 2008. A highly divergent picornavirus in a marine mammal. J. Virol. 82: 311320.
37. Karst, S. M.,, C. E. Wobus,, M. Lay,, J. Davidson, and, H. W. Virgin IV. 2003. STAT1-dependent innate immunity to a Norwalk-like virus. Science 299: 15751578.
38. Kassem, A.,, A. Schöpflin,, C. Diaz,, W. Weyers,, E. Stickeler,, M. Werner, and, A. zur Hausen. 2008. Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res. 68: 50095013.
39. Kistler, A.,, P. C. Avila,, S. Rouskin,, D. Wang,, T. Ward,, S. Yagi,, D. Schnurr,, D. Ganem,, J. L. DeRisi, and, H. A. Boushey. 2007. Pan-viral screening of respiratory tract infections in adults with and without asthma reveals unexpected human coronavirus and human rhinovirus diversity. J. Infect. Dis. 196: 817825.
40. Kistler, A. L.,, A. Gancz,, S. Clubb,, P. Skewes-Cox,, K. Fischer,, K. Sorber,, C. Y. Chiu,, A. Lublin,, S. Mechani,, Y. Farnoushi,, A. Greninger,, C. C. Wen,, S. B. Karlene,, D. Ganem, and, J. L. DeRisi. 2008. Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: identification of a candidate etiologic agent. Virol. J. 5: 88.
41. Korimbocus, J.,, N. Scaramozzino,, B. Lacroix,, J. M. Crance,, D. Garin, and, G. Vernet. 2005. DNA probe array for the simultaneous identification of herpesviruses, enteroviruses, and flaviviruses. J. Clin. Microbiol. 43: 37793787.
42. Ksiazek, T. G.,, D. Erdman,, C. S. Goldsmith,, S. R. Zaki,, T. Peret,, S. Emery,, S. Tong,, C. Urbani,, J. A. Comer,, W. Lim,, P. E. Rollin,, S. F. Dowell,, A. E. Ling,, C. D. Humphrey,, W. J. Shieh,, J. Guarner,, C. D. Paddock,, P. Rota,, B. Fields,, J. DeRisi,, J. Y. Yang,, N. Cox,, J. M. Hughes,, J. W. LeDuc,, W. J. Bellini, and, L. J. Anderson. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 348: 19531966.
43. Le, B. M.,, L. M. Demertzis,, G. Wu,, R. J. Tibbets,, R. Buller,, M. Q. Arens,, A. M. Gaynor,, G. A. Storch, and, D. Wang. 2007. Clinical and epidemiologic characterization of WU polyomavirus infection, St. Louis, Missouri. Emerg. Infect. Dis. 13: 19361938.
44. Lemos, B.,, and P. Nghiem. 2007. Merkel cell carcinoma: more deaths but still no pathway to blame. J. Invest. Dermatol. 127: 21002103.
45. Lin, B.,, Z. Wang,, G. J. Vora,, J. A. Thornton,, J. M. Schnur,, D. C. Thach,, K. M. Blaney,, A. G. Ligler,, A. P. Malanoski,, J. Santiago,, E. A. Walter,, B. K. Agan,, D. Metzgar,, D. Seto,, L. T. Daum,, R. Kruzelock,, R. K. Rowley,, E. H. Hanson,, C. Tibbetts, and, D. A. Stenger. 2006. Broad-spectrum respiratory tract pathogen identification 651 using resequencing DNA microarrays. Genome Res. 16: 527535.
46. Lin, F.,, M. Zheng,, H. Li,, C. Zheng,, X. Li,, G. Rao,, M. Zheng,, F. Wu, and, A. Zeng. 2008. WU polyomavirus in children with acute lower respiratory tract infections, China. J. Clin. Virol. 42: 94102.
47. Lindner, J.,, and S. Modrow. 2008. Human bocavirus—a novel parvovirus to infect humans. Intervirology 51: 116122.
48. Lisitsyn, N.,, N. Lisitsyn, and, M. Wigler. 1993. Cloning the differences between two complex genomes. Science 259: 946951.
49. Mardis, E. R. 2008. The impact of next-generation sequencing technology on genetics. Trends Genet. 24: 133141.
50. Maskos, U.,, and E. M. Southern. 1992. Oligonucleotide hybridizations on glass supports: a novel linker for oligonucleotide synthesis and hybridization properties of oligonucleotides synthesised in situ. Nucleic Acids Res. 20: 16791684.
51. Mihindukulasuriya, K. A.,, G. Wu,, J. St. Leger,, R. W. Nordhausen, and, D. Wang. 2008. Identification of a novel coronavirus from a beluga whale by using a panviral microarray. J. Virol. 82: 50845088.
52. Monceyron, C.,, B. Grinde, and, T. O. Jonassen. 1997. Molecular characterisation of the 3′-end of the astrovirus genome. Arch. Virol. 142: 699706.
53. Neske, F.,, K. Blessing,, F. Ullrich,, A. Pröttel,, H. Wolfgang Kreth, and, B. Weissbrich. 2008. WU polyomavirus infection in children, Germany. Emerg. Infect. Dis. 14: 680681.
54. Nichol, S. T.,, C. F. Spiropoulou,, S. Morzunov,, P. E. Rollin,, T. G. Ksiazek,, H. Feldmann,, A. Sanchez,, J. Childs,, S. Zaki, and, C. J. Peters. 1993. Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness. Science 262: 914917.
55. Palacios, G.,, J. Druce,, L. Du,, T. Tran,, C. Birch,, T. Briese,, S. Conlan,, P. L. Quan,, J. Hui,, J. Marshall,, J. F. Simons,, M. Egholm,, C. D. Paddock,, W. J. Shieh,, C. S. Goldsmith,, S. R. Zaki,, M. Catton, and, W. I. Lipkin. 2008. A new arenavirus in a cluster of fatal transplant-associated diseases. N. Engl. J. Med. 358: 991998.
56. Palacios, G.,, P. L. Quan,, O. J. Jabado,, S. Conlan,, D. L. Hirschberg,, Y. Liu,, J. Zhai,, N. Renwick,, J. Hui,, H. Hegyi,, A. Grolla,, J. E. Strong,, J. S. Towner,, T. W. Geisbert,, P. B. Jahrling,, C. Buchen-Osmond,, H. Ellerbrok,, M. P. Sanchez-Seco,, Y. Lussier,, P. Formenty,, M. S. Nichol,, H. Feldmann,, T. Briese, and, W. I. Lipkin. 2007. Panmicrobial oligonucleotide array for diagnosis of infectious diseases. Emerg. Infect. Dis. 13: 7381.
57. Payungporn, S.,, T. Chieochansin,, C. Thongmee,, R. Samransamruajkit,, A. Theamboolers, and, Y. Poovorawan. 2008. Prevalence and molecular characterization of WU/KI polyomaviruses isolated from pediatric patients with respiratory disease in Thailand. Virus Res. 135: 230236.
58. Peiris, J. S.,, S. T. Lai,, L. L. Poon,, Y. Guan,, L. Y. Yam,, W. Lim,, J. Nicholls,, W. K. Yee,, W. W. Yan,, M. T. Cheung,, V. C. Cheng,, K. H. Chan,, D. N. Tsang,, R. W. Yung,, T. K. Ng, and, K. Y. Yuen. 2003. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361: 13191325.
59. Poulin, D. L.,, and J. A. DeCaprio. 2006. Is there a role for SV40 in human cancer? J. Clin. Oncol. 24: 43564365.
60. Ralph, D.,, M. McClelland, and, J. Welsh. 1993. RNA fingerprinting using arbitrarily primed PCR identifies differentially regulated RNAs in mink lung (Mv1Lu) cells growth arrested by transforming growth factor β1. Proc. Natl. Acad. Sci. USA 90: 1071010714.
61. Rehrauer, H.,, S. Schönmann,, L. Eberl, and, R. Schlapbach. 2008. PhyloDetect: a likelihood-based strategy for detecting microorganisms with diagnostic microarrays. Bioinformatics 24: i83i89.
62. Rennert, H.,, D. Bercovich,, A. Hubert,, D. Abeliovich,, U. Rozovsky,, A. Bar-Shira,, S. Soloviov,, L. Schreiber,, H. Matzkin,, G. Rennert,, L. Kadouri,, T. Peretz,, Y. Yaron, and, A. Orr-Urtreger. 2002. A novel founder mutation in the RNASEL gene, 471delAAAG, is associated with prostate cancer in Ashkenazi Jews. Am. J. Hum. Genet. 71: 981984.
63. Reyes, G. R.,, and J. P. Kim. 1991. Sequence-independent, single-primer amplification (SISPA) of complex DNA populations. Mol. Cell. Probes 5: 473481.
64. Rökman, A.,, T. Ikonen,, E. H. Seppälä,, N. Nupponen,, V. Autio,, N. Mononen,, J. Bailey-Wilson,, J. Trent,, J. Carpten,, M. P. Matikainen,, P. A. Koivisto,, T. L. Tammela,, O. P. Kallioniemi, and, J. Schleutker. 2002. Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer. Am. J. Hum. Genet. 70: 12991304.
65. Ronaghi, M.,, S. Karamohamed,, B. Pettersson,, M. Uhlen, and, P. Nyren. 1996. Real-time DNA sequencing using detection of pyrophosphate release. Anal. Biochem. 242: 8489.
66. Rose, T. M.,, E. R. Schultz,, J. G. Henikoff,, S. Pietrokovski,, C. M. McCallum, and, S. Henikoff. 1998. Consensus-degenerate hybrid oligonucleotide primers for amplification of distantly related sequences. Nucleic Acids Res. 26: 16281635.
67. Sanger, F.,, S. Nicklen, and, A. R. Coulson. 1977. DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA 74: 54635467.
68. Schena, M. 1996. Genome analysis with gene expression microarrays. Bioessays 18: 427431.
69. Urisman, A.,, K. F. Fischer,, C. Y. Chiu,, A. L. Kistler,, S. Beck,, D. Wang, and, J. L. DeRisi. 2005. E-Predict: a computational strategy for species identification based on observed DNA microarray hybridization patterns. Genome Biol. 6: R78.
70. Urisman, A.,, R. J. Molinaro,, N. Fischer,, S. J. Plummer,, G. Casey,, E. A. Klein,, K. Malathi,, C. Magi-Galluzzi,, R. R. Tubbs,, D. Ganem,, R. H. Silverman, and, J. L. DeRisi. 2006. Identification of a novel gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant. PLoS Pathog. 2: e25.
71. van den Hoogen, B. G.,, J. C. de Jong,, J. Groen,, T. Kuiken,, R. de Groot,, R. A. Fouchier, and, A. D. Osterhaus. 2001. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat. Med. 7: 719724.
72. van der Hoek, L.,, K. Pyrc,, M. F. Jebbink,, W. Vermeulen-Oost,, R. J. Berkhout,, K. C. Wolthers,, P. M. Wertheim-van Dillen,, J. Kaandorp,, J. Spaargaren, and, B. Berkhout. 2004. Identification of a new human coronavirus. Nat. Med. 10: 368373.
73. van der Hoek, L.,, K. Sure,, G. Ihorst,, A. Stang,, K. Pyrc,, M. F. Jebbink,, G. Petersen,, J. Forster,, B. Berkhout, and, K. Uberla. 2005. Croup is associated with the novel coronavirus NL63. PLoS Med. 2: e240.
74. Wang, D.,, L. Coscoy,, M. Zylberberg,, P. C. Avila,, H. A. Boushey,, D. Ganem, and, J. L. DeRisi. 2002. Microarray-based detection and genotyping of viral pathogens. Proc. Natl. Acad. Sci. USA 99: 1568715692.
75. Wang, D.,, A. Urisman,, Y. T. Liu,, M. Springer,, T. G. Ksiazek,, D. D. Erdman,, E. R. Mardis,, M. Hickenbotham,, V. Magrini,, J. Eldred,, J. P. Latreille,, R. K. Wilson,, D. Ganem, and, J. L. DeRisi. 2003. Viral discovery and sequence recovery using DNA microarrays. PLoS Biol. 1: e2.
76. Watson, M.,, J. Dukes,, A. B. Abu-Median,, D. P. King, and, P. Britton. 2007. DetectiV: visualization, normalization and significance testing for pathogen-detection microarray data. Genome Biol. 8: R190.
77. Welsh, J.,, and M. McClelland. 1990. Fingerprinting genomes using PCR with arbitrary primers. Nucleic Acids Res. 18: 72137218.
78. Wommack, K. E.,, J. Bhavsar, and, J. Ravel. 2008. Metagenomics: read length matters. Appl. Environ. Microbiol. 74: 14531463.
79. Wong, C. W.,, C. L. Heng,, L. Wan Yee,, S. W. Soh,, C. B. Kartasasmita,, E. A. Simoes,, M. L. Hibberd,, W. K. Sung, and, L. D. Miller. 2007. Optimization and clinical validation of a pathogen detection microarray. Genome Biol. 8: R93.
80. Woo, P. C.,, S. K. Lau,, C. M. Chu,, K. H. Chan,, H. W. Tsoi,, Y. Huang,, B. H. Wong,, R. W. Poon,, J. J. Cai,, W. K. Luk,, L. L. Poon,, S. S. Wong,, Y. Guan,, J. S. Peiris, and, K. Y. Yuen. 2005. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J. Virol. 79: 884895.
81. Xu, Y.,, N. Stange-Thomann,, G. Weber,, R. Bo,, S. Dodge,, R. G. David,, K. Foley,, J. Beheshti,, N. L. Harris,, B. Birren,, E. S. Lander, and, M. Meyerson. 2003. Pathogen discovery from human tissue by sequence-based computational subtraction. Genomics 81: 329335.
82. Zhang, T.,, M. Breitbart,, W. H. Lee,, J. Q. Run,, C. L. Wei,, S. W. Soh,, M. L. Hibberd,, E. T. Liu,, F. Rohwer, and, Y. Ruan. 2006. RNA viral community in human feces: prevalence of plant pathogenic viruses. PLoS Biol. 4: e3.

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