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Next Generation Sequencing: Chemistry, Technology and Applications

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Book cover Chemical Diagnostics

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 336))

Abstract

High-throughput next generation sequencing (NGS) has been quickly adapted into many aspects of biomedical research and begun to engage with the clinical practice. The latter aspect will enable the application of genomic knowledge into clinical practice in this and next decades and will profoundly change the diagnosis, prognosis and treatment of many human diseases. It will further demand both philosophical and medical curriculum reforms in the training of our future physicians. However, significant huddles need to be overcome before an ultimate application of NGS in genomic medicine can be practical and fruitful.

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References

  1. International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431(7011):931–945

    Article  Google Scholar 

  2. Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455(7216):1061–1068

    Article  Google Scholar 

  3. Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M et al (2008) DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 456(7218):66–72

    Article  CAS  Google Scholar 

  4. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L et al (2004) EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 101(36):13306–13311

    Article  CAS  Google Scholar 

  5. Dietz HC (2010) New therapeutic approaches to mendelian disorders. N Engl J Med 363(9):852–863

    Article  CAS  Google Scholar 

  6. Green ED, Guyer MS (2011) Charting a course for genomic medicine from base pairs to bedside. Nature 470(7333):204–213

    Article  CAS  Google Scholar 

  7. Hawkins RD, Hon GC, Ren B (2010) Next-generation genomics: an integrative approach. Nat Rev Genet 11(7):476–486

    CAS  Google Scholar 

  8. Shendure J, Ji H (2008) Next-generation DNA sequencing. Nat Biotechnol 26(10):1135–1145

    Article  CAS  Google Scholar 

  9. Martinez DA, Nelson MA (2010) The next generation becomes the now generation. PLoS Genet 6(4):e1000906

    Article  Google Scholar 

  10. Voelkerding KV, Dames SA, Durtschi JD (2009) Next-generation sequencing: from basic research to diagnostics. Clin Chem 55(4):641–658

    Article  CAS  Google Scholar 

  11. Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, He W, Chen YJ, Makhijani V, Roth GT et al (2008) The complete genome of an individual by massively parallel DNA sequencing. Nature 452(7189):872–876

    Article  CAS  Google Scholar 

  12. Niedringhaus TP, Milanova D, Kerby MB, Snyder MP, Barron AE (2011) Landscape of next-generation sequencing technologies. Anal Chem 83(12):4327–4341

    Article  CAS  Google Scholar 

  13. Fuller CW, Middendorf LR, Benner SA, Church GM, Harris T, Huang X, Jovanovich SB, Nelson JR, Schloss JA, Schwartz DC et al (2009) The challenges of sequencing by synthesis. Nat Biotechnol 27(11):1013–1023

    Article  CAS  Google Scholar 

  14. Ekblom R, Galindo J (2011) Applications of next generation sequencing in molecular ecology of non-model organisms. Heredity 107(1):1–15

    Article  CAS  Google Scholar 

  15. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 74(12):5463–5467

    Article  CAS  Google Scholar 

  16. Maxam AM, Gilbert W (1977) A new method for sequencing DNA. Proc Natl Acad Sci U S A 74(2):560–564

    Article  CAS  Google Scholar 

  17. Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, Axelrod N, Huang J, Kirkness EF, Denisov G et al (2007) The diploid genome sequence of an individual human. PLoS Biol 5(10):e254

    Article  Google Scholar 

  18. Metzker ML (2010) Sequencing technologies – the next generation. Nat Rev Genet 11(1):31–46

    Article  CAS  Google Scholar 

  19. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, Berka J, Braverman MS, Chen YJ, Chen Z et al (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437(7057):376–380

    CAS  Google Scholar 

  20. Schuster SC (2008) Next-generation sequencing transforms today’s biology. Nat Methods 5(1):16–18

    Article  CAS  Google Scholar 

  21. Ronaghi M, Uhlen M, Nyren P (1998) A sequencing method based on real-time pyrophosphate. Science 281(5375):363–365

    Article  CAS  Google Scholar 

  22. Mardis ER (2008) Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet 9:387–402

    Article  CAS  Google Scholar 

  23. Valouev A, Ichikawa J, Tonthat T, Stuart J, Ranade S, Peckham H, Zeng K, Malek JA, Costa G, McKernan K et al (2008) A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. Genome Res 18(7):1051–1063

    Article  CAS  Google Scholar 

  24. Wu H, Irizarry RA, Bravo HC (2010) Intensity normalization improves color calling in SOLiD sequencing. Nat Methods 7(5):336–337

    Article  CAS  Google Scholar 

  25. Efcavitch JW, Thompson JF (2010) Single-molecule DNA analysis. Annu Rev Anal Chem (Palo Alto Calif) 3:109–128

    Article  CAS  Google Scholar 

  26. Thompson JF, Milos PM (2011) The properties and applications of single-molecule DNA sequencing. Genome Biol 12(2):217

    CAS  Google Scholar 

  27. Harris TD, Buzby PR, Babcock H, Beer E, Bowers J, Braslavsky I, Causey M, Colonell J, Dimeo J, Efcavitch JW et al (2008) Single-molecule DNA sequencing of a viral genome. Science 320(5872):106–109

    Article  CAS  Google Scholar 

  28. Eid J, Fehr A, Gray J, Luong K, Lyle J, Otto G, Peluso P, Rank D, Baybayan P, Bettman B et al (2009) Real-time DNA sequencing from single polymerase molecules. Science 323(5910):133–138

    Article  CAS  Google Scholar 

  29. Lundquist PM, Zhong CF, Zhao P, Tomaney AB, Peluso PS, Dixon J, Bettman B, Lacroix Y, Kwo DP, McCullough E et al (2008) Parallel confocal detection of single molecules in real time. Opt Lett 33(9):1026–1028

    Article  Google Scholar 

  30. Korlach J, Marks PJ, Cicero RL, Gray JJ, Murphy DL, Roitman DB, Pham TT, Otto GA, Foquet M, Turner SW (2008) Selective aluminum passivation for targeted immobilization of single DNA polymerase molecules in zero-mode waveguide nanostructures. Proc Natl Acad Sci U S A 105(4):1176–1181

    Article  CAS  Google Scholar 

  31. Korlach J, Bjornson KP, Chaudhuri BP, Cicero RL, Flusberg BA, Gray JJ, Holden D, Saxena R, Wegener J, Turner SW (2010) Real-time DNA sequencing from single polymerase molecules. Methods Enzymol 472:431–455

    CAS  Google Scholar 

  32. Munroe DJ, Harris TJ (2010) Third-generation sequencing fireworks at Marco Island. Nat Biotechnol 28(5):426–428

    Article  CAS  Google Scholar 

  33. Flusberg BA, Webster DR, Lee JH, Travers KJ, Olivares EC, Clark TA, Korlach J, Turner SW (2010) Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat Methods 7(6):461–465

    Article  CAS  Google Scholar 

  34. Uemura S, Aitken CE, Korlach J, Flusberg BA, Turner SW, Puglisi JD (2010) Real-time tRNA transit on single translating ribosomes at codon resolution. Nature 464(7291):1012–1017

    Article  CAS  Google Scholar 

  35. Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL, Kermani BG, Carnevali P, Nazarenko I, Nilsen GB, Yeung G et al (2010) Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 327(5961):78–81

    Article  CAS  Google Scholar 

  36. Porreca GJ (2010) Genome sequencing on nanoballs. Nat Biotechnol 28(1):43–44

    Article  CAS  Google Scholar 

  37. Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, Rowen L, Pant KP, Goodman N, Bamshad M et al (2010) Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328(5978):636–639

    Article  CAS  Google Scholar 

  38. Lee W, Jiang Z, Liu J, Haverty PM, Guan Y, Stinson J, Yue P, Zhang Y, Pant KP, Bhatt D et al (2010) The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature 465(7297):473–477

    Article  CAS  Google Scholar 

  39. Rothberg JM, Hinz W, Rearick TM, Schultz J, Mileski W, Davey M, Leamon JH, Johnson K, Milgrew MJ, Edwards M et al (2011) An integrated semiconductor device enabling non-optical genome sequencing. Nature 475(7356):348–352

    Article  CAS  Google Scholar 

  40. Clarke J, Wu HC, Jayasinghe L, Patel A, Reid S, Bayley H (2009) Continuous base identification for single-molecule nanopore DNA sequencing. Nat Nanotechnol 4(4):265–270

    Article  CAS  Google Scholar 

  41. Stoddart D, Heron AJ, Mikhailova E, Maglia G, Bayley H (2009) Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore. Proc Natl Acad Sci U S A 106(19):7702–7707

    Article  CAS  Google Scholar 

  42. Branton D, Deamer DW, Marziali A, Bayley H, Benner SA, Butler T, Di Ventra M, Garaj S, Hibbs A, Huang X et al (2008) The potential and challenges of nanopore sequencing. Nat Biotechnol 26(10):1146–1153

    Article  CAS  Google Scholar 

  43. Bayley H (2006) Sequencing single molecules of DNA. Curr Opin Chem Biol 10(6):628–637

    Article  CAS  Google Scholar 

  44. Astier Y, Braha O, Bayley H (2006) Toward single molecule DNA sequencing: direct identification of ribonucleoside and deoxyribonucleoside 5'-monophosphates by using an engineered protein nanopore equipped with a molecular adapter. J Am Chem Soc 128(5):1705–1710

    Article  CAS  Google Scholar 

  45. Manolio TA (2010) Genomewide association studies and assessment of the risk of disease. N Engl J Med 363(2):166–176

    Article  CAS  Google Scholar 

  46. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, Green T, Kuballa P, Barmada MM, Datta LW et al (2007) Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39(5):596–604

    Article  CAS  Google Scholar 

  47. Van Limbergen J, Wilson DC, Satsangi J (2009) The genetics of Crohn’s disease. Annu Rev Genomics Hum Genet 10:89–116

    Article  Google Scholar 

  48. Hoffmann TJ, Kvale MN, Hesselson SE, Zhan Y, Aquino C, Cao Y, Cawley S, Chung E, Connell S, Eshragh J et al (2011) Next generation genome-wide association tool: design and coverage of a high-throughput European-optimized SNP array. Genomics 98(2):79–89

    Article  CAS  Google Scholar 

  49. Need AC, Goldstein DB (2009) Next generation disparities in human genomics: concerns and remedies. Trends Genet 25(11):489–494

    Article  CAS  Google Scholar 

  50. Miller W, Hayes VM, Ratan A, Petersen DC, Wittekindt NE, Miller J, Walenz B, Knight J, Qi J, Zhao F et al (2011) Genetic diversity and population structure of the endangered marsupial Sarcophilus harrisii (Tasmanian devil). Proc Natl Acad Sci U S A 108(30):12348–12353

    Article  CAS  Google Scholar 

  51. Zalapa JE, Cuevas H, Zhu H, Steffan S, Senalik D, Zeldin E, McCown B, Harbut R, Simon P (2012) Using next-generation sequencing approaches to isolate simple sequence repeat (SSR) loci in the plant sciences. Am J Bot 99:193–208

    Article  CAS  Google Scholar 

  52. Mohandas N, Gallagher PG (2008) Red cell membrane: past, present, and future. Blood 112(10):3939–3948

    Article  CAS  Google Scholar 

  53. Hershberger RE, Siegfried JD (2011) Update 2011: clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol 57(16):1641–1649

    Article  CAS  Google Scholar 

  54. Kingsmore SF, Dinwiddie DL, Miller NA, Soden SE, Saunders CJ (2011) Adopting orphans: comprehensive genetic testing of Mendelian diseases of childhood by next-generation sequencing. Expert Rev Mol Diagn 11(8):855–868

    Article  CAS  Google Scholar 

  55. Tsurusaki Y, Okamoto N, Suzuki Y, Doi H, Saitsu H, Miyake N, Matsumoto N (2011) Exome sequencing of two patients in a family with atypical X-linked leukodystrophy. Clin Genet 80(2):161–166

    Article  CAS  Google Scholar 

  56. Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, Saitsu H, Matsumoto N, Miyake N (2011) Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing. J Med Genet 48(9):606–609

    Article  CAS  Google Scholar 

  57. Schraders M, Haas SA, Weegerink NJ, Oostrik J, Hu H, Hoefsloot LH, Kannan S, Huygen PL, Pennings RJ, Admiraal RJ et al (2011) Next-generation sequencing identifies mutations of SMPX, which encodes the small muscle protein, X-linked, as a cause of progressive hearing impairment. Am J Hum Genet 88(5):628–634

    Article  CAS  Google Scholar 

  58. Hu H, Wrogemann K, Kalscheuer V, Tzschach A, Richard H, Haas SA, Menzel C, Bienek M, Froyen G, Raynaud M et al (2009) Mutation screening in 86 known X-linked mental retardation genes by droplet-based multiplex PCR and massive parallel sequencing. Hugo J 3(1–4):41–49

    Article  CAS  Google Scholar 

  59. Jones MA, Bhide S, Chin E, Ng BG, Rhodenizer D, Zhang VW, Sun JJ, Tanner A, Freeze HH, Hegde MR (2011) Targeted polymerase chain reaction-based enrichment and next generation sequencing for diagnostic testing of congenital disorders of glycosylation. Genet Med 13(11):921–932

    Article  CAS  Google Scholar 

  60. Doi H, Yoshida K, Yasuda T, Fukuda M, Fukuda Y, Morita H, Ikeda S, Kato R, Tsurusaki Y, Miyake N et al (2011) Exome sequencing reveals a homozygous SYT14 mutation in adult-onset, autosomal-recessive spinocerebellar ataxia with psychomotor retardation. Am J Hum Genet 89(2):320–327

    Article  CAS  Google Scholar 

  61. Artuso R, Fallerini C, Dosa L, Scionti F, Clementi M, Garosi G, Massella L, Epistolato MC, Mancini R, Mari F et al (2012) Advances in Alport syndrome diagnosis using next-generation sequencing. Eur J Hum Genet 20(1):50–57

    Article  CAS  Google Scholar 

  62. Bowne SJ, Sullivan LS, Koboldt DC, Ding L, Fulton R, Abbott RM, Sodergren EJ, Birch DG, Wheaton DH, Heckenlively JR et al (2011) Identification of disease-causing mutations in autosomal dominant retinitis pigmentosa (adRP) using next-generation DNA sequencing. Invest Ophthalmol Vis Sci 52(1):494–503

    Article  CAS  Google Scholar 

  63. Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloglu A, Ozen S, Sanjad S et al (2009) Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci U S A 106(45):19096–19101

    Article  CAS  Google Scholar 

  64. Choi M, Scholl UI, Yue P, Bjorklund P, Zhao B, Nelson-Williams C, Ji W, Cho Y, Patel A, Men CJ et al (2011) K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science 331(6018):768–772

    Article  CAS  Google Scholar 

  65. Bell CJ, Dinwiddie DL, Miller NA, Hateley SL, Ganusova EE, Mudge J, Langley RJ, Zhang L, Lee CC, Schilkey FD et al (2011) Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci Transl Med 3(65):65ra4

    Article  CAS  Google Scholar 

  66. Park PJ (2009) ChIP-seq: advantages and challenges of a maturing technology. Nat Rev Genet 10(10):669–680

    Article  CAS  Google Scholar 

  67. Fouse SD, Nagarajan RP, Costello JF (2010) Genome-scale DNA methylation analysis. Epigenomics 2(1):105–117

    Article  CAS  Google Scholar 

  68. Meaburn E, Schulz R (2011) Next generation sequencing in epigenetics: insights and challenges. Semin Cell Dev Biol 23:192–199

    Google Scholar 

  69. Ku CS, Naidoo N, Wu M, Soong R (2011) Studying the epigenome using next generation sequencing. J Med Genet 48(11):721–730

    Article  CAS  Google Scholar 

  70. Gibbons JG, Janson EM, Hittinger CT, Johnston M, Abbot P, Rokas A (2009) Benchmarking next-generation transcriptome sequencing for functional and evolutionary genomics. Mol Biol Evol 26(12):2731–2744

    Article  CAS  Google Scholar 

  71. Martin JA, Wang Z (2011) Next-generation transcriptome assembly. Nat Rev Genet 12(10):671–682

    Article  CAS  Google Scholar 

  72. Levin JZ, Berger MF, Adiconis X, Rogov P, Melnikov A, Fennell T, Nusbaum C, Garraway LA, Gnirke A (2009) Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcripts. Genome Biol 10(10):R115

    Article  Google Scholar 

  73. Tripathy S, Jiang RH (2012) Massively parallel sequencing technology in pathogenic microbes. Methods Mol Biol 835:271–294

    CAS  Google Scholar 

  74. Mellmann A, Harmsen D, Cummings CA, Zentz EB, Leopold SR, Rico A, Prior K, Szczepanowski R, Ji Y, Zhang W et al (2011) Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology. PLoS One 6(7):e22751

    Article  CAS  Google Scholar 

  75. Hu B, Xie G, Lo CC, Starkenburg SR, Chain PS (2011) Pathogen comparative genomics in the next-generation sequencing era: genome alignments, pangenomics and metagenomics. Brief Funct Genomics 10(6):322–333

    Article  CAS  Google Scholar 

  76. Barzon L, Lavezzo E, Militello V, Toppo S, Palu G (2011) Applications of next-generation sequencing technologies to diagnostic virology. Int J Mol Sci 12(11):7861–7884

    Article  CAS  Google Scholar 

  77. Barzon L, Militello V, Lavezzo E, Franchin E, Peta E, Squarzon L, Trevisan M, Pagni S, Dal Bello F, Toppo S et al (2011) Human papillomavirus genotyping by 454 next generation sequencing technology. J Clin Virol 52(2):93–97

    Article  CAS  Google Scholar 

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The author does not have any funding support or financial interest to declare.

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Authors and Affiliations

  1. Department of Pathology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT, 06520-8023, USA

    Pei Hui

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  1. Pei Hui
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Correspondence to Pei Hui .

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Editors and Affiliations

  1. Dept. of Chemical Pathology and Lab. of Genetics of Disease Suscept., The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    Nelson L.S. Tang

  2. Department of Paediatrics and Proteomics Laboratory, The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    Terence Poon

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© 2012 Springer-Verlag Berlin Heidelberg

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Hui, P. (2012). Next Generation Sequencing: Chemistry, Technology and Applications. In: L.S. Tang, N., Poon, T. (eds) Chemical Diagnostics. Topics in Current Chemistry, vol 336. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2012_329

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