Chapter 14 : Microbial Genomics and Pathogen Discovery

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This chapter discusses the concepts of microbial genomics and pathogen discovery. The discussion begins with an overview of traditional efforts, followed by a brief description of the evolution of sequencing technologies. Finally, the chapter illustrates how the two fields began to intersect in the first few years of the 21st century. The discoveries of Hepatitis C virus (HCV) and Human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma-associated herpesvirus (KSHV), represented two breakthroughs in the application of candidate-independent molecular methods for pathogen discovery. The onset of the 21st century has seen the convergence of the fields of pathogen discovery and microbial genomics. The PhyloChip, a high-density 16S rRNA microarray containing 300,000 probes, was used to examine the microbial diversity in three environmental samples, including urban aerosol, subsurface soil, and subsurface water. This study demonstrated that the array could reveal broader diversity than classical cloning and sequencing of the same sample. The challenge facing the scientific community for the remainder of this century is to develop commensurate approaches to defining the biological relevance of this multitude of novel microbes to human disease.

Citation: Gaynor A, Wang D. 2011. Microbial Genomics and Pathogen Discovery, p 199-209. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch14
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Major landmarks in pathogen discovery and microbial genomics. RDA, representational difference analysis; RAP-PCR, random arbitrarily primed PCR; VIDISCA, virus discovery cDNA-AFLP (amplified restriction fragment length polymorphism).

Citation: Gaynor A, Wang D. 2011. Microbial Genomics and Pathogen Discovery, p 199-209. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch14
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1. Allander, T.,, K. Andreasson,, S. Gupta,, A. Bjerkner,, G. Bogdanovic,, M. A. A. Persson,, T. Dalianis,, T. Ramqvist,, and B. Andersson. 2007. Identification of a third human polyomavirus. J. Virol. 81: 4130 4136.
2. 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: 11609 11614.
3. 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: 12891 12896.
3a. Allred, A. F.,, G. Wu,, T. Wulan,, K. F. Fischer,, M. R. Holbrook,, R. B. Tesh,, and D. Wang. 2010. VIPR: a probabilistic algorithm for analysis of microbial detection bioarrays. BMC Bioinformatics 11: 384.
4. Al-Sunaidi, M.,, C. H. Williams,, P. J. Hughes,, D. P. Schnurr,, and G. Stanway. 2007. Analysis of a new human parechovirus allows the definition of parechovirus types and the identification of RNA structural domains. J. Virol. 81: 1013 1021.
5. Arthur, J. L.,, G. D. Higgins,, G. P. Davidson,, R. C. Givney,, and R. M. Ratcliff. 2009. A novel bocavirus associated with acute gastroenteritis in Australian children. PLoS Pathog. 5: e1000391.
6. Barrette, R. W.,, S. A. Metwally,, J. M. Rowland,, L. Xu,, S. R. Zaki,, S. T. Nichol,, P. E. Rollin,, J. S. Towner,, W. J. Shieh,, B. Batten,, T. K. Sealy,, C. Carrillo,, K. E. Moran,, A. J. Bracht,, G. A. Mayr,, M. Sirios-Cruz,, D. P. Catbagan,, E. A. Lautner,, T. G. Ksiazek,, W. R. White,, and M. T. McIntosh. 2009. Discovery of swine as a host for the Reston ebolavirus. Science 325: 204 206.
7. Baumgarte, S.,, L. K. de Souza Luna,, K. Grywna,, M. Panning,, J. F. Drexler,, C. Karsten,, H. I. Huppertz,, and C. Drosten. 2008. Prevalence, types, and RNA concentrations of human parechoviruses, including a sixth parechovirus type, in stool samples from patients with acute enteritis. J. Clin. Microbiol. 46: 242 248.
8. Benschop, K. S.,, J. Schinkel,, M. E. Luken,, P. J. van den Broek,, M. F. Beersma,, N. Menelik,, H. W. vanEijk,, H. L. Zaaijer,, C. M. Van den Broucke-Grauls,, M. G. Beld,, and K. C. Wolthers. 2006. Fourth human parechovirus serotype. Emerg. Infect. Dis. 12: 1572 1575.
9. Breitbart, M.,, and F. Rohwer. 2005. Method for discovering novel DNA viruses in blood using viral particle selection and shotgun sequencing. BioTechniques 39: 729 736.
10. Briese, T.,, J. T. Paweska,, L. K. McMullan,, S. K. Hutchison,, C. Street,, G. Palacios,, M. L. Khristova,, J. Weyer,, R. Swanepoel,, M. Egholm,, S. T. Nichol,, and W. I. Lipkin. 2009. Genetic detection and characterization of Lujo virus, a new hemorrhagic fever-associated arenavirus from southern Africa. PLoS Pathog. 5: e1000455.
11. Brosius, J.,, M. L. Palmer,, P. J. Kennedy,, and H. F. Noller. 1978. Complete nucleotide sequence of a 16S ribosomal RNA gene from Escherichia coli. Proc. Natl. Acad. Sci. USA 75: 4801 4805.
12. The C. elegans Sequencing Consortium. 1998. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282: 20122018.
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: 1865 1869.
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 pan-virus microarray. J. Clin. Microbiol. 45: 2340 2343.
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: 14124 14129.
16. Chiu, C. Y.,, S. Rouskin,, A. Koshy,, A. Urisman,, K. Fischer,, S. Yagi,, D. Schnurr,, P. B. Eckburg,, L. S. Tompkins,, B. G. Blackburn,, J. D. Merker,, B. K. Patterson,, D. Ganem,, and J. L. DeRisi. 2006. Microarray detection of human parainfluenzavirus 4 infection associated with respiratory failure in an immunocompetent adult. Clin. Infect. Dis. 43: e71 e76.
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: 359 362.
18. Deffrasnes, C.,, M. E. Hamelin,, and G. Boivin. 2007. Human metapneumovirus. Semin. Respir. Crit. Care Med. 28: 213 221.
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. DeRisi, J. L.,, V. R. Iyer,, and P. O. Brown. 1997. Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278: 680 686.
21. DeSantis, T. Z.,, E. L. Brodie,, J. P. Moberg,, I. X. Zubieta,, Y. M. Piceno,, and G. L. Andersen. 2007. High-density universal 16S rRNA microarray analysis reveals broader diversity than typical clone library when sampling the environment. Microb. Ecol. 53: 371 383.
22. Dijkman, R.,, M. F. Jebbink,, N. B. El Idrissi,, K. Pyrc,, M. A. Muller,, T. W. Kuijpers,, H. L. Zaaijer,, and L. van der Hoek. 2008. Human coronavirus NL63 and 229E seroconversion in children. J. Clin. Microbiol. 46: 2368 2373.
23. Drexler, J. F.,, K. Grywna,, A. Stöcker,, P. S. Almeida,, T. C. Medrado Ribeiro,, M. Eschbach-Bludau,, N. Petersen,, H. da Costa Ribeiro, Jr., and C. Drosten. 2009. Novel human parechovirus from Brazil. Emerg. Infect. Dis. 15: 310 313.
24. Drexler, J. F.,, L. K. Luna,, A. Stöcker,, P. S. Almeida,, T. C. Medrado 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: 1398 1405.
25. Eisen, M. B.,, P. T. Spellman,, P. O. Brown,, and D. Botstein. 1998. Cluster analysis and display of genome-wide expression patterns. Proc. Natl. Acad. Sci. USA 95: 14863 14868.
26. Endo, R.,, N. Ishiguro,, H. Kikuta,, S. Teramoto,, R. Shirkoohi,, X. Ma,, T. Ebihara,, H. Ishiko,, and T. Ariga. 2007. Seroepidemiology of human bocavirus in Hokkaido prefecture, Japan. J. Clin. Microbiol. 45: 3218 3223.
27. Feng, H.,, M. Shuda,, Y. Chang,, and P. S. Moore. 2008. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319: 1096 1100.
28. Finkbeiner, S. R.,, C. D. Kirkwood,, and D. Wang. 2008. Complete genome sequence of a highly divergent astrovirus isolated from a child with acute diarrhea. Virol. J. 5: 117.
29. Finkbeiner, S. R.,, B. M. Le,, L. R. Holtz,, G. A. Storch,, and D. Wang. 2009. Detection of newly described astrovirus MLB1 in stool samples from children. Emerg. Infect. Dis. 15: 441 444.
30. Finkbeiner, S. R.,, Y. Li,, S. Ruone,, C. Conrardy,, N. Gregoricus,, D. Toney,, H. W. Virgin,, L. J. Anderson,, J. Vinje,, D. Wang,, and S. Tong. 2009. Identification of a novel astrovirus (astrovirus VA1) associated with an outbreak of acute gastroenteritis. J. Virol. 83: 10836 10839.
31. Fleischmann, R. D.,, M. D. Adams,, O. White,, R. A. Clayton,, E. F. Kirkness,, A. R. Kerlavage,, C. J. Bult,, J. F. Tomb,, B. A. Dougherty,, J. M. Merrick, et al. 1995. Wholegenome random sequencing and assembly of Haemophilus influenzae Rd. Science 269: 496 512.
32. Fouchier, R. A.,, V. Munster,, A. Wallensten,, T. M. Bestebroer,, S. Herfst,, D. Smith,, G. F. Rimmelzwaan,, B. Olsen,, and A. D. Osterhaus. 2005. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J. Virol. 79: 2814 2822.
33. Fredericks, D. N.,, and D. A. Relman. 1996. Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clin. Microbiol. Rev. 9: 18 33.
34. 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.
35. Goffeau, A.,, B. G. Barrell,, H. Bussey,, R. W. Davis,, B. Dujon,, H. Feldmann,, F. Galibert,, J. D. Hoheisel,, C. Jacq,, M. Johnston,, E. J. Louis,, H. W. Mewes,, Y. Murakami,, P. Philippsen,, H. Tettelin,, and S. G. Oliver. 1996. Life with 6000 genes. Science 274: 546, 563 567.
36. Greninger, A. L.,, C. Runckel,, C. Y. Chiu,, T. Haggerty,, J. Parsonnet,, D. Ganem,, and J. L. DeRisi. 2009. The complete genome of klassevirus—a novel picornavirus in pediatric stool. Virol. J. 6: 82.
37. Hales, L. M.,, N. J. Knowles,, P. S. Reddy,, L. Xu,, C. Hay,, and P. L. Hallenbeck. 2008. Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus. J. Gen. Virol. 89: 1265 1275.
38. Holtz, L. R.,, S. R. Finkbeiner,, C. D. Kirkwood,, and D. Wang. 2008. Identification of a novel picornavirus related to cosaviruses in a child with acute diarrhea. Virol. J. 5: 159.
39. Holtz, L. R.,, S. R. Finkbeiner,, G. Zhao,, C. D. Kirkwood,, R. Girones,, J. M. Pipas,, and D. Wang. 2009. Klassevirus 1, a previously undescribed member of the family Picornaviridae, is globally widespread. Virol. J. 6: 86.
40. Ito, M.,, T. Yamashita,, H. Tsuzuki,, N. Takeda,, and K. Sakae. 2004. Isolation and identification of a novel human parechovirus. J. Gen. Virol. 85: 391 398.
41. 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: 8230 8236.
42. 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: 2144 2150.
43. Kantola, K.,, L. Hedman,, T. Allander,, T. Jartti,, P. Lehtinen,, O. Ruuskanen,, K. Hedman,, and M. Soderlund-Venermo. 2008. Serodiagnosis of human bocavirus infection. Clin. Infect. Dis. 46: 540 546.
44. Kapoor, A.,, E. Slikas,, P. Simmonds,, T. Chieochansin,, A. Naeem,, S. Shaukat,, M. M. Alam,, S. Sharif,, M. Angez,, S. Zaidi,, and E. Delwart. 2009. A newly identified bocavirus species in human stool. J. Infect. Dis. 199: 196 200.
45. Kapoor, A.,, J. Victoria,, P. Simmonds,, E. Slikas,, T. Chieochansin,, A. Naeem,, S. Shaukat,, S. Sharif,, M. M. Alam,, M. Angez,, C. Wang,, R. W. Shafer,, S. Zaidi,, and E. Delwart. 2008. A highly prevalent and genetically diversified Picornaviridae genus in South Asian children. Proc. Natl. Acad. Sci. USA 105: 20482 20487.
46. Kim, S.,, N. Kim,, B. Dong,, D. Boren,, S. A. Lee,, J. Das Gupta,, C. Gaughan,, E. A. Klein,, C. Lee,, R. H. Silverman,, and S. A. Chow. 2008. Integration site preference of xenotropic murine leukemia virus-related virus, a new human retrovirus associated with prostate cancer. J. Virol. 82: 9964 9977.
47. 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: 817 825.
48. 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: 1953 1966.
49. Lamson, D.,, N. Renwick,, V. Kapoor,, Z. Liu,, G. Palacios,, J. Ju,, A. Dean,, K. St. George,, T. Briese,, and W. I. Lipkin. 2006. MassTag polymerase-chain-reaction detection of respiratory pathogens, including a new rhinovirus genotype, that caused influenza-like illness in New York State during 2004– 2005. J. Infect. Dis. 194: 1398 1402.
50. Lander, E. S.,, L. M. Linton,, B. Birren,, C. Nusbaum,, M. C. Zody,, J. Baldwin,, K. Devon,, K. Dewar,, M. Doyle,, W. FitzHugh,, R. Funke,, D. Gage,, K. Harris,, A. Heaford,, J. Howland,, L. Kann,, J. Lehoczky,, R. LeVine,, P. McEwan,, K. McKernan,, J. Meldrim,, J. P. Mesirov,, C. Miranda,, W. Morris,, J. Naylor,, C. Raymond,, M. Rosetti,, R. Santos,, A. Sheridan,, C. Sougnez,, N. Stange-Thomann,, N. Stojanovic,, A. Subramanian,, D. Wyman,, J. Rogers,, J. Sulston,, R. Ainscough,, S. Beck,, D. Bentley,, J. Burton,, C. Clee,, N. Carter,, A. Coulson,, R. Deadman,, P. Deloukas,, A. Dunham,, I. Dunham,, R. Durbin,, L. French,, D. Grafham,, S. Gregory,, T. Hubbard,, S. Humphray,, A. Hunt,, M. Jones,, C. Lloyd,, A. McMurray,, L. Matthews,, S. Mercer,, S. Milne,, J. C. Mullikin,, A. Mungall,, R. Plumb,, M. Ross,, R. Shownkeen,, S. Sims,, R. H. Waterston,, R. K. Wilson,, L. W. Hillier,, J. D. McPherson,, M. A. Marra,, E. R. Mardis,, L. A. Fulton,, A. T. Chinwalla,, K. H. Pepin,, W. R. Gish,, S. L. Chissoe,, M. C. Wendl,, K. D. Delehaunty,, T. L. Miner,, A. Delehaunty,, J. B. Kramer,, L. L. Cook,, R. S. Fulton,, D. L. Johnson,, P. J. Minx,, S. W. Clifton,, T. Hawkins,, E. Branscomb,, P. Predki,, P. Richardson,, S. Wenning,, T. Slezak,, N. Doggett,, J. F. Cheng,, A. Olsen,, S. Lucas,, C. Elkin,, E. Uberbacher,, M. Frazier, et al. 2001. Initial sequencing and analysis of the human genome. Nature 409: 860 921.
51. Lau, S. K.,, C. C. Yip,, H. W. Tsoi,, R. A. Lee,, L. Y. So,, Y. L. Lau,, K. H. Chan,, P. C. Woo,, and K. Y. Yuen. 2007. Clinical features and complete genome characterization of a distinct human rhinovirus (HRV) genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children. J. Clin. Microbiol. 45: 3655 3664.
52. Lee, W. M.,, C. Kiesner,, T. Pappas,, I. Lee,, K. Grindle,, T. Jartti,, B. Jakiela,, R. F. Lemanske, Jr.,, P. A. Shult,, and J. E. Gern. 2007. A diverse group of previously unrecognized human rhinoviruses are common causes of respiratory illnesses in infants. PLoS ONE 2: e966.
53. Ley, R. E.,, F. Backhed,, P. Turnbaugh,, C. A. Lozupone,, R. D. Knight,, and J. I. Gordon. 2005. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 102: 11070 11075.
54. Ley, R. E.,, P. J. Turnbaugh,, S. Klein,, and J. I. Gordon. 2006. Microbial ecology: human gut microbes associated with obesity. Nature 444: 1022 1023.
55. Li, L.,, J. Victoria,, A. Kapoor,, A. Naeem,, S. Shaukat,, S. Sharif,, M. M. Alam,, M. Angez,, S. Z. Zaidi,, and E. Delwart. 2009. Genomic characterization of novel human parechovirus type. Emerg. Infect. Dis. 15: 288 291.
56. Lin, B.,, A. P. Malanoski,, Z. Wang,, K. M. Blaney,, A. G. Ligler,, R. K. Rowley,, E. H. Hanson,, E. von Rosenvinge,, F. S. Ligler,, A. W. Kusterbeck,, D. Metzgar,, C. P. Barrozo,, K. L. Russell,, C. Tibbetts,, J. M. Schnur,, and D. A. Stenger. 2007. Application of broad-spectrum, sequence-based pathogen identification in an urban population. PLoS ONE 2: e419.
57. Lombardi, V. C.,, F. W. Ruscetti,, J. Das Gupta,, M. A. Pfost,, K. S. Hagen,, D. L. Peterson,, S. K. Ruscetti,, R. K. Bagni,, C. Petrow-Sadowski,, B. Gold,, M. Dean,, R. H. Silverman,, and J. A. Mikovits. 2009. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 326: 585 589.
58. Mardis, E. R. 2008. Next-generation DNA sequencing methods. Annu. Rev. Genomics Hum. Genet. 9: 387 402.
59. McErlean, P.,, L. A. Shackelton,, S. B. Lambert,, M. D. Nissen,, T. P. Sloots,, and I. M. Mackay. 2007. Characterisation of a newly identified human rhinovirus, HRV-QPM, discovered in infants with bronchiolitis. J. Clin. Virol. 39: 67 75.
60. Nguyen, N. L.,, B. M. Le,, and D. Wang. 2009. Serologic evidence of frequent human infection with WU and KI polyomaviruses. Emerg Infect Dis. 15: 1199 1205.
61. 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: 914 917.
62. 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: 73 81.
63. Palmer, C.,, E. M. Bik,, D. B. DiGiulio,, D. A. Relman,, and P. O. Brown. 2007. Development of the human infant intestinal microbiota. PLoS Biol. 5: e177.
64. Quan, P. L.,, G. Palacios,, O. J. Jabado,, S. Conlan,, D. L. Hirschberg,, F. Pozo,, P. J. Jack,, D. Cisterna,, N. Renwick,, J. Hui,, A. Drysdale,, R. Amos-Ritchie,, E. Baumeister,, V. Savy,, K. M. Lager,, J. A. Richt,, D. B. Boyle,, A. Garcia- Sastre,, I. Casas,, P. Perez-Brena,, T. Briese,, and W. I. Lipkin. 2007. Detection of respiratory viruses and subtype identification of influenza A viruses by GreeneChipResp oligonucleotide microarray. J. Clin. Microbiol. 45: 2359 2364.
65. Raoult, D.,, S. Audic,, C. Robert,, C. Abergel,, P. Renesto,, H. Ogata,, B. La Scola,, M. Suzan,, and J. M. Claverie. 2004. The 1.2-megabase genome sequence of Mimivirus. Science 306: 1344 1350.
66. Rehrauer, H.,, S. Schonmann,, L. Eberl,, and R. Schlapbach. 2008. PhyloDetect: a likelihood-based strategy for detecting microorganisms with diagnostic microarrays. Bioinformatics 24: i83 i89.
67. Relman, D. A.,, J. S. Loutit,, T. M. Schmidt,, S. Falkow,, and L. S. Tompkins. 1990. The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens. N. Engl. J. Med. 323: 1573 1580.
68. Relman, D. A.,, T. M. Schmidt,, R. P. MacDermott,, and S. Falkow. 1992. Identification of the uncultured bacillus of Whipple’s disease. N. Engl. J. Med. 327: 293 301.
69. Rota, P. A.,, M. S. Oberste,, S. S. Monroe,, W. A. Nix,, R. Campagnoli,, J. P. Icenogle,, S. Penaranda,, B. Bankamp,, K. Maher,, M. H. Chen,, S. Tong,, A. Tamin,, L. Lowe,, M. Frace,, J. L. DeRisi,, Q. Chen,, D. Wang,, D. D. Erdman,, T. C. Peret,, C. Burns,, T. G. Ksiazek,, P. E. Rollin,, A. Sanchez,, S. Liffick,, B. Holloway,, J. Limor,, K. McCaustland,, M. Olsen-Rasmussen,, R. Fouchier,, S. Gunther,, A. D. Osterhaus,, C. Drosten,, M. A. Pallansch,, L. J. Anderson,, and W. J. Bellini. 2003. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300: 1394 1399.
70. Towner, J. S.,, T. K. Sealy,, M. L. Khristova,, C. G. Albarino,, S. Conlan,, S. A. Reeder,, P. L. Quan,, W. I. Lipkin,, R. Downing,, J. W. Tappero,, S. Okware,, J. Lutwama,, B. Bakamutumaho,, J. Kayiwa,, J. A. Comer,, P. E. Rollin,, T. G. Ksiazek,, and S. T. Nichol. 2008. Newly discovered Ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog. 4: e1000212.
71. 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.
72. 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.
73. van den Hoogen, B. G.,, J. C. deJong,, 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: 719 724.
74. van der Hoek, L.,, K. Pyrc,, M. F. Jebbink,, W. Vermeulen- Oost,, R. J. Berkhout,, K. C. Wolthers,, P. M. Wertheimvan Dillen,, J. Kaandorp,, J. Spaargaren,, and B. Berkhout. 2004. Identification of a new human coronavirus. Nat. Med. 10: 368 373.
75. Venter, J. C.,, M. D. Adams,, E. W. Myers,, P. W. Li,, R. J. Mural,, G. G. Sutton,, H. O. Smith,, M. Yandell,, C. A. Evans,, R. A. Holt,, J. D. Gocayne,, P. Amanatides,, R. M. Ballew,, D. H. Huson,, J. R. Wortman,, Q. Zhang,, C. D. Kodira,, X. H. Zheng,, L. Chen,, M. Skupski,, G. Subramanian,, P. D. Thomas,, J. Zhang,, G. L. Gabor Miklos,, C. Nelson,, S. Broder,, A. G. Clark,, J. Nadeau,, V. A. McKusick,, N. Zinder,, A. J. Levine,, R. J. Roberts,, M. Simon,, C. Slayman,, M. Hunkapiller,, R. Bolanos,, A. Delcher,, I. Dew,, D. Fasulo,, M. Flanigan,, L. Florea,, A. Halpern,, S. Hannenhalli,, S. Kravitz,, S. Levy,, C. Mobarry,, K. Reinert,, K. Remington,, J. Abu-Threideh,, E. Beasley,, K. Biddick,, V. Bonazzi,, R. Brandon,, M. Cargill,, I. Chandramouliswaran,, R. Charlab,, K. Chaturvedi,, Z. Deng,, V. Di Francesco,, P. Dunn,, K. Eilbeck,, C. Evangelista,, A. E. Gabrielian,, W. Gan,, W. Ge,, F. Gong,, Z. Gu,, P. Guan,, T. J. Heiman,, M. E. Higgins,, R. R. Ji,, Z. Ke,, K. A. Ketchum,, Z. Lai,, Y. Lei,, Z. Li,, J. Li,, Y. Liang,, X. Lin,, F. Lu,, G. V. Merkulov,, N. Milshina,, H. M. Moore,, A. K. Naik,, V. A. Narayan,, B. Neelam,, D. Nusskern,, D. B. Rusch,, S. Salzberg,, W. Shao,, B. Shue,, J. Sun,, Z. Wang,, A. Wang,, X. Wang,, J. Wang,, M. Wei,, R. Wides,, C. Xiao,, C. Yan, et al. 2001. The sequence of the human genome. Science 291: 1304 1351.
76. Wang, D.,, L. Coscoy,, M. Zylberberg,, P. C. Avila,, H. A. Boushey,, D. Ganem,, and J. L. DeRisi. 2002. Microarraybased detection and genotyping of viral pathogens. Proc. Natl. Acad. Sci. USA 99: 15687 15692.
77. 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.
78. Watanabe, K.,, M. Oie,, M. Higuchi,, M. Nishikawa,, and M. Fujii. 2007. Isolation and characterization of novel human parechovirus from clinical samples. Emerg. Infect. Dis. 13: 889 895.
79. 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.
80. Woese, C. R.,, and G. E. Fox. 1977. Phylogenetic structure of the prokaryotic domain: the primary kingdoms. Proc. Natl. Acad. Sci. USA 74: 5088 5090.
81. 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.
82. 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: 884 895.
83. Zoll, J.,, S. Erkens Hulshof,, K. Lanke,, F. Verduyn Lunel,, W. J. Melchers,, E. Schoondermark-van deVen,, M. Roivainen,, J. M. Galama,, and F. J. vanKuppeveld. 2009. Saffold virus, a human Theiler’s-like cardiovirus, is ubiquitous and causes infection early in life. PLoS Pathog. 5: e1000416.

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