The term next-generation sequencing is almost a decade old, but it remains the colloquial way to describe highly parallel or high-output sequencing methods that produce data at or beyond the genome scale. Since the introduction of these technologies, the number of applications and methods that leverage the power of genome-scale sequencing has increased at an exponential pace. This review highlights recent concepts, technologies, and methods from next-generation sequencing to illustrate the breadth and depth of the applications and research areas that are driving progress in genomics.

Keyword(s): exomesequencingwhole genome

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Literature Cited

  1. 1. 1000 Genomes Proj. Consort 2012. An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65 [Google Scholar]
  2. Acevedo A, Andino R. 2.  2014. Library preparation for highly accurate population sequencing of RNA viruses. Nat. Protoc. 9:1760–69 [Google Scholar]
  3. Adey A, Kitzman JO, Burton JN, Daza R, Kumar A. 3.  et al. 2014. In vitro, long-range sequence information for de novo genome assembly via transposase contiguity. Genome Res 24:2041–49 [Google Scholar]
  4. Albert TJ, Molla MN, Muzny DM, Nazareth L, Wheeler D. 4.  et al. 2007. Direct selection of human genomic loci by microarray hybridization. Nat. Methods 4:903–5 [Google Scholar]
  5. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S. 5.  et al. 2013. Signatures of mutational processes in human cancer. Nature 500:415–21 [Google Scholar]
  6. Alexandrov LB, Nik-Zainal S, Wedge DC, Campbell PJ, Stratton MR. 6.  2013. Deciphering signatures of mutational processes operative in human cancer. Cell Rep 3:246–59 [Google Scholar]
  7. Alexandrov LB, Stratton MR. 7.  2014. Mutational signatures: the patterns of somatic mutations hidden in cancer genomes. Curr. Opin. Genet. Dev. 24:52–60 [Google Scholar]
  8. Amini S, Pushkarev D, Christiansen L, Kostem E, Royce T. 8.  et al. 2014. Haplotype-resolved whole-genome sequencing by contiguity-preserving transposition and combinatorial indexing. Nat. Genet. 46:1343–49 [Google Scholar]
  9. Ashley EA, Butte AJ, Wheeler MT, Chen R, Klein TE. 9.  et al. 2010. Clinical assessment incorporating a personal genome. Lancet 375:1525–35 [Google Scholar]
  10. Ashton PM, Nair S, Dallman T, Rubino S, Rabsch W. 10.  et al. 2015. MinION nanopore sequencing identifies the position and structure of a bacterial antibiotic resistance island. Nat. Biotechnol. 33:296–300 [Google Scholar]
  11. Au KF, Sebastiano V. 11.  2014. The transcriptome of human pluripotent stem cells. Curr. Opin. Genet. Dev. 28:71–77 [Google Scholar]
  12. Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J. 12.  et al. 2008. Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456:53–59 [Google Scholar]
  13. Branton D, Deamer DW, Marziali A, Bayley H, Benner SA. 13.  et al. 2008. The potential and challenges of nanopore sequencing. Nat. Biotechnol. 26:1146–53 [Google Scholar]
  14. Burghel GJ, Hurst CD, Watson CM, Chambers PA, Dickinson H. 14.  et al. 2015. Towards a next-generation sequencing diagnostic service for tumour genotyping: a comparison of panels and platforms. Biomed. Res. Int. 2015:478017 [Google Scholar]
  15. Cao MD, Ganesamoorthy D, Cooper MA, Coin LJM. 15.  2016. Realtime analysis and visualization of MinION sequencing data with npReader. Bioinformatics 32:764–66 [Google Scholar]
  16. Carneiro MO, Russ C, Ross MG, Gabriel SB, Nusbaum C, DePristo MA. 16.  2012. Pacific Biosciences sequencing technology for genotyping and variation discovery in human data. BMC Genom. 13:375 [Google Scholar]
  17. Chaisson MJ, Huddleston J, Dennis MY, Sudmant PH, Malig M. 17.  et al. 2015. Resolving the complexity of the human genome using single-molecule sequencing. Nature 517:608–11 [Google Scholar]
  18. Chaisson MJ, Wilson RK, Eichler EE. 18.  2015. Genetic variation and the de novo assembly of human genomes. Nat. Rev. Genet. 16:627–40 [Google Scholar]
  19. Chang CJ, Chen PL, Yang WS, Chao KM. 19.  2014. A fault-tolerant method for HLA typing with PacBio data. BMC Bioinform. 15:296 [Google Scholar]
  20. Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR. 20.  et al. 2009. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. PNAS 106:19096–101 [Google Scholar]
  21. Church DM, Schneider VA, Steinberg KM, Schatz MC, Quinlan AR. 21.  et al. 2015. Extending reference assembly models. Genome Biol 16:13 [Google Scholar]
  22. Church GM, Gao Y, Kosuri S. 22.  2012. Next-generation digital information storage in DNA. Science 337:1628 [Google Scholar]
  23. Compeau PE, Pevzner PA, Tesler G. 23.  2011. How to apply de Bruijn graphs to genome assembly. Nat. Biotechnol. 29:987–91 [Google Scholar]
  24. Darmanis S, Sloan SA, Zhang Y, Enge M, Caneda C. 24.  et al. 2015. A survey of human brain transcriptome diversity at the single cell level. PNAS 112:7285–90 [Google Scholar]
  25. Dewey FE, Grove ME, Pan C, Goldstein BA, Bernstein JA. 25.  et al. 2014. Clinical interpretation and implications of whole-genome sequencing. JAMA 311:1035–45 [Google Scholar]
  26. Dohm JC, Lottaz C, Borodina T, Himmelbauer H. 26.  2008. Substantial biases in ultra-short read data sets from high-throughput DNA sequencing. Nucleic Acids Res 36:e105 [Google Scholar]
  27. Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL. 27.  et al. 2010. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 327:78–81 [Google Scholar]
  28. Duitama J, McEwen GK, Huebsch T, Palczewski S, Schulz S. 28.  et al. 2012. Fosmid-based whole genome haplotyping of a HapMap trio child: evaluation of single individual haplotyping techniques. Nucleic Acids Res 40:2041–53 [Google Scholar]
  29. Eid J, Fehr A, Gray J, Luong K, Lyle J. 29.  et al. 2009. Real-time DNA sequencing from single polymerase molecules. Science 323:133–38 [Google Scholar]
  30. English AC, Richards S, Han Y, Wang M, Vee V. 30.  et al. 2012. Mind the gap: upgrading genomes with Pacific Biosciences RS long-read sequencing technology. PLOS ONE 7:e47768 [Google Scholar]
  31. Erlich Y. 31.  2015. A vision for ubiquitous sequencing. Genome Res 25:1411–16 [Google Scholar]
  32. Exome Aggregation Consort., Lek M, Karczewski KJ, Minikel EV, Samocha KE. 32.  et al. 2015. Analysis of protein-coding genetic variation in 60,706 humans. bioRxiv. doi: 10.1101/030338
  33. Fang G, Munera D, Friedman DI, Mandlik A, Chao MC. 33.  et al. 2012. Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing. Nat. Biotechnol. 30:1232–39 [Google Scholar]
  34. Farlik M, Sheffield NC, Nuzzo A, Datlinger P, Schonegger A. 34.  et al. 2015. Single-cell DNA methylome sequencing and bioinformatic inference of epigenomic cell-state dynamics. Cell Rep 10:1386–97 [Google Scholar]
  35. Flusberg BA, Webster DR, Lee JH, Travers KJ, Olivares EC. 35.  et al. 2010. Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat. Methods 7:461–65 [Google Scholar]
  36. Fu W, O'Connor TD, Jun G, Kang HM, Abecasis G. 36.  et al. 2013. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature 493:216–20 [Google Scholar]
  37. Fu Y, Li C, Lu S, Zhou W, Tang F. 37.  et al. 2015. Uniform and accurate single-cell sequencing based on emulsion whole-genome amplification. PNAS 112:11923–28 [Google Scholar]
  38. Garnett MJ, McDermott U. 38.  2014. The evolving role of cancer cell line-based screens to define the impact of cancer genomes on drug response. Curr. Opin. Genet. Dev. 24:114–19 [Google Scholar]
  39. Gaublomme JT, Yosef N, Lee Y, Gertner RS, Yang LV. 39.  et al. 2015. Single-cell genomics unveils critical regulators of Th17 cell pathogenicity. Cell 163:1400–12 [Google Scholar]
  40. 40. Genome Ref. Consort 2015. Human genome overview: information concerning the continuing improvement of the human genome. http://www.ncbi.nlm.nih.gov/projects/genome/assembly/grc/human
  41. Gnirke A, Melnikov A, Maguire J, Rogov P, LeProust EM. 41.  et al. 2009. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nat. Biotechnol. 27:182–89 [Google Scholar]
  42. Goodwin S, Gurtowski J, Ethe-Sayers S, Deshpande P, Schatz MC, McCombie WR. 42.  2015. Oxford Nanopore sequencing, hybrid error correction, and de novo assembly of a eukaryotic genome. Genome Res 25:1750–56 [Google Scholar]
  43. Gudbjartsson DF, Helgason H, Gudjonsson SA, Zink F, Oddson A. 43.  et al. 2015. Large-scale whole-genome sequencing of the Icelandic population. Nat. Genet. 47:435–44 [Google Scholar]
  44. Gulcher J, Stefansson K. 44.  1998. Population genomics: laying the groundwork for genetic disease modeling and targeting. Clin. Chem. Lab. Med. 36:523–27 [Google Scholar]
  45. Gulcher J, Stefansson K. 45.  1999. An Icelandic saga on a centralized healthcare database and democratic decision making. Nat. Biotechnol. 17:620 [Google Scholar]
  46. Gundersen S, Kalas M, Abul O, Frigessi A, Hovig E, Sandve GK. 46.  2011. Identifying elemental genomic track types and representing them uniformly. BMC Bioinform. 12:494 [Google Scholar]
  47. Guo J, Xu N, Li Z, Zhang S, Wu J. 47.  et al. 2008. Four-color DNA sequencing with 3′-O-modified nucleotide reversible terminators and chemically cleavable fluorescent dideoxynucleotides. PNAS 105:9145–50 [Google Scholar]
  48. Harris TD, Buzby PR, Babcock H, Beer E, Bowers J. 48.  et al. 2008. Single-molecule DNA sequencing of a viral genome. Science 320:106–9 [Google Scholar]
  49. Helleday T, Eshtad S, Nik-Zainal S. 49.  2014. Mechanisms underlying mutational signatures in human cancers. Nat. Rev. Genet. 15:585–98 [Google Scholar]
  50. Hodges E, Xuan Z, Balija V, Kramer M, Molla MN. 50.  et al. 2007. Genome-wide in situ exon capture for selective resequencing. Nat. Genet. 39:1522–27 [Google Scholar]
  51. Honeyman JN, Simon EP, Robine N, Chiaroni-Clarke R, Darcy DG. 51.  et al. 2014. Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma. Science 343:1010–14 [Google Scholar]
  52. Huddleston J, Ranade S, Malig M, Antonacci F, Chaisson M. 52.  et al. 2014. Reconstructing complex regions of genomes using long-read sequencing technology. Genome Res 24:688–96 [Google Scholar]
  53. 53. Illumina 2014. Sequencing methods review: a review of publications featuring Illumina® Technology Publ. No. 073-2014-001, Illumina, San Diego, CA. http://www.illumina.com/techniques/sequencing/ngs-library-prep/library-prep-methods.html
  54. 54. Int. Hum. Genome Seq. Consort 2004. Finishing the euchromatic sequence of the human genome. Nature 431:931–45 [Google Scholar]
  55. Jain M, Fiddes IT, Miga KH, Olsen HE, Paten B, Akeson M. 55.  2015. Improved data analysis for the MinION nanopore sequencer. Nat. Methods 12:351–56 [Google Scholar]
  56. Kaper F, Swamy S, Klotzle B, Munchel S, Cottrell J. 56.  et al. 2013. Whole-genome haplotyping by dilution, amplification, and sequencing. PNAS 110:5552–57 [Google Scholar]
  57. Karamitros T, Magiorkinis G. 57.  2015. A novel method for the multiplexed target enrichment of MinION next generation sequencing libraries using PCR-generated baits. Nucleic Acids Res. 43:e152 [Google Scholar]
  58. Karow J. 58.  2015. Oxford Nanopore outlines specs for new sequencers, automated sample prep system, pay-as-go pricing. Genome Web May 15. http://www.genomeweb.com/sequencing- technology/oxford-nanopore-outlines-specs-new-sequencers-automated-sample-prep-system-pay
  59. Kasianowicz JJ, Brandin E, Branton D, Deamer DW. 59.  1996. Characterization of individual polynucleotide molecules using a membrane channel. PNAS 93:13770–73 [Google Scholar]
  60. Koren S, Schatz MC, Walenz BP, Martin J, Howard JT. 60.  et al. 2012. Hybrid error correction and de novo assembly of single-molecule sequencing reads. Nat. Biotechnol. 30:693–700 [Google Scholar]
  61. Ku CS, Polychronakos C, Tan EK, Naidoo N, Pawitan Y. 61.  et al. 2013. A new paradigm emerges from the study of de novo mutations in the context of neurodevelopmental disease. Mol. Psychiatry 18:141–53 [Google Scholar]
  62. Kuleshov V, Jiang C, Zhou W, Jahanbani F, Batzoglou S, Snyder M. 62.  2016. Synthetic long-read sequencing reveals intraspecies diversity in the human microbiome. Nat. Biotechnol. 34:64–69 [Google Scholar]
  63. Kuleshov V, Xie D, Chen R, Pushkarev D, Ma Z. 63.  et al. 2014. Whole-genome haplotyping using long reads and statistical methods. Nat. Biotechnol. 32:261–66 [Google Scholar]
  64. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC. 64.  et al. 2001. Initial sequencing and analysis of the human genome. Nature 409:860–921 [Google Scholar]
  65. Leinonen R, Sugawara H, Shumway M. 65. (Int. Nucleotide Seq. Database Consort.) 2011. The sequence read archive. Nucleic Acids Res 39:D19–21 [Google Scholar]
  66. Lelieveld SH, Spielmann M, Mundlos S, Veltman JA, Gilissen C. 66.  2015. Comparison of exome and genome sequencing technologies for the complete capture of protein-coding regions. Hum. Mutat. 36:815–22 [Google Scholar]
  67. Levene MJ, Korlach J, Turner SW, Foquet M, Craighead HG, Webb WW. 67.  2003. Zero-mode waveguides for single-molecule analysis at high concentrations. Science 299:682–86 [Google Scholar]
  68. Li H. 68.  2014. On the graphical representation of sequences. Heng Li's Blog July 25. http://lh3.github.io/2014/07/25/on-the-graphical-representation-of-sequences
  69. Li Q, Li Y, Song J, Xu H, Xu J. 69.  et al. 2014. High-accuracy de novo assembly and SNP detection of chloroplast genomes using a SMRT circular consensus sequencing strategy. New Phytol. 204:1041–49 [Google Scholar]
  70. Liu L, Li Y, Li S, Hu N, He Y. 70.  et al. 2012. Comparison of next-generation sequencing systems. J. Biomed. Biotechnol. 2012:251364 [Google Scholar]
  71. Loomis EW, Eid JS, Peluso P, Yin J, Hickey L. 71.  et al. 2013. Sequencing the unsequenceable: expanded CGG-repeat alleles of the fragile X gene. Genome Res 23:121–28 [Google Scholar]
  72. Lou DI, Hussmann JA, McBee RM, Acevedo A, Andino R. 72.  et al. 2013. High-throughput DNA sequencing errors are reduced by orders of magnitude using circle sequencing. PNAS 110:19872–77 [Google Scholar]
  73. Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC. 73.  et al. 2010. Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N. Engl. J. Med. 362:1181–91 [Google Scholar]
  74. Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K. 74.  et al. 2015. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161:1202–14 [Google Scholar]
  75. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS. 75.  et al. 2005. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437:376–80 [Google Scholar]
  76. Maxam AM, Gilbert W. 76.  1977. A new method for sequencing DNA. PNAS 74:560–64 [Google Scholar]
  77. Mellmann A, Harmsen D, Cummings CA, Zentz EB, Leopold SR. 77.  et al. 2011. Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology. PLOS ONE 6:e22751 [Google Scholar]
  78. Metzker ML. 78.  2010. Sequencing technologies—the next generation. Nat. Rev. Genet. 11:31–46 [Google Scholar]
  79. Meynert AM, Ansari M, FitzPatrick DR, Taylor MS. 79.  2014. Variant detection sensitivity and biases in whole genome and exome sequencing. BMC Bioinform. 15:247 [Google Scholar]
  80. Morey M, Fernandez-Marmiesse A, Castineiras D, Fraga JM, Couce ML, Cocho JA. 80.  2013. A glimpse into past, present, and future DNA sequencing. Mol. Genet. Metab. 110:3–24 [Google Scholar]
  81. Munro SA, Lund SP, Pine PS, Binder H, Clevert DA. 81.  et al. 2014. Assessing technical performance in differential gene expression experiments with external spike-in RNA control ratio mixtures. Nat. Commun. 5:5125 [Google Scholar]
  82. Myers EW. 82.  2005. The fragment assembly string graph. Bioinform. 21:Suppl. 2ii79–85 [Google Scholar]
  83. Navin NE. 83.  2014. Cancer genomics: one cell at a time. Genome Biol 15:452 [Google Scholar]
  84. Neale BM, Kou Y, Liu L, Ma'ayan A, Samocha KE. 84.  et al. 2012. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 485:242–45 [Google Scholar]
  85. Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK. 85.  et al. 2010. Exome sequencing identifies the cause of a Mendelian disorder. Nat. Genet. 42:30–35 [Google Scholar]
  86. Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW. 86.  et al. 2009. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461:272–76 [Google Scholar]
  87. Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD. 87.  et al. 2012. Mutational processes molding the genomes of 21 breast cancers. Cell 149:979–93 [Google Scholar]
  88. Offit K. 88.  2014. Decade in review—genomics: a decade of discovery in cancer genomics. Nat. Rev. Clin. Oncol. 11:632–34 [Google Scholar]
  89. Okou DT, Steinberg KM, Middle C, Cutler DJ, Albert TJ, Zwick ME. 89.  2007. Microarray-based genomic selection for high-throughput resequencing. Nat. Methods 4:907–9 [Google Scholar]
  90. Patwardhan A, Harris J, Leng N, Bartha G, Church DM. 90.  et al. 2015. Achieving high-sensitivity for clinical applications using augmented exome sequencing. Genome Med 7:71 [Google Scholar]
  91. Pease AC, Solas D, Sullivan EJ, Cronin MT, Holmes CP, Fodor SP. 91.  1994. Light-generated oligonucleotide arrays for rapid DNA sequence analysis. PNAS 91:5022–26 [Google Scholar]
  92. Peters BA, Kermani BG, Sparks AB, Alferov O, Hong P. 92.  et al. 2012. Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells. Nature 487:190–95 [Google Scholar]
  93. Porreca GJ, Zhang K, Li JB, Xie B, Austin D. 93.  et al. 2007. Multiplex amplification of large sets of human exons. Nat. Methods 4:931–36 [Google Scholar]
  94. Quail MA, Smith M, Coupland P, Otto TD, Harris SR. 94.  et al. 2012. A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genom. 13:341 [Google Scholar]
  95. Quick J, Quinlan AR, Loman NJ. 95.  2014. A reference bacterial genome dataset generated on the MinION portable single-molecule nanopore sequencer. GigaScience 3:22 [Google Scholar]
  96. Reuter JA, Spacek DV, Snyder MP. 96.  2015. High-throughput sequencing technologies. Mol. Cell 58:586–97 [Google Scholar]
  97. Risse J, Thomson M, Patrick S, Blakely G, Koutsovoulos G. 97.  et al. 2015. A single chromosome assembly of Bacteroides fragilis strain BE1 from Illumina and MinION nanopore sequencing data. GigaScience 4:60 [Google Scholar]
  98. Roach JC, Glusman G, Smit AF, Huff CD, Hubley R. 98.  et al. 2010. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328:636–39 [Google Scholar]
  99. Robert C, Watson M. 99.  2015. Errors in RNA-Seq quantification affect genes of relevance to human disease. Genome Biol. 16:177 [Google Scholar]
  100. Rotem A, Ram O, Shoresh N, Sperling RA, Goren A. 100.  et al. 2015. Single-cell ChIP-seq reveals cell subpopulations defined by chromatin state. Nat. Biotechnol. 33:1165–72 [Google Scholar]
  101. Rothberg JM, Hinz W, Rearick TM, Schultz J, Mileski W. 101.  et al. 2011. An integrated semiconductor device enabling non-optical genome sequencing. Nature 475:348–52 [Google Scholar]
  102. Rydbeck H, Sandve GK, Ferkingstad E, Simovski B, Rye M, Hovig E. 102.  2015. ClusTrack: feature extraction and similarity measures for clustering of genome-wide data sets. PLOS ONE 10:e0123261 [Google Scholar]
  103. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R. 103.  et al. 1988. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–91 [Google Scholar]
  104. Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT. 104.  et al. 1985. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–54 [Google Scholar]
  105. Samocha KE, Robinson EB, Sanders SJ, Stevens C, Sabo A. 105.  et al. 2014. A framework for the interpretation of de novo mutation in human disease. Nat. Genet. 46:944–50 [Google Scholar]
  106. Sanger F, Coulson AR. 106.  1975. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J. Mol. Biol. 94:441–48 [Google Scholar]
  107. Shalon D, Smith SJ, Brown PO. 107.  1996. A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. Genome Res 6:639–45 [Google Scholar]
  108. Sharon D, Tilgner H, Grubert F, Snyder M. 108.  2013. A single-molecule long-read survey of the human transcriptome. Nat. Biotechnol. 31:1009–14 [Google Scholar]
  109. Shendure J, Porreca GJ, Reppas NB, Lin X, McCutcheon JP. 109.  et al. 2005. Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309:1728–32 [Google Scholar]
  110. Simon EP, Freije CA, Farber BA, Lalazar G, Darcy DG. 110.  et al. 2015. Transcriptomic characterization of fibrolamellar hepatocellular carcinoma. PNAS 112:E5916–25 [Google Scholar]
  111. Smallwood SA, Lee HJ, Angermueller C, Krueger F, Saadeh H. 111.  et al. 2014. Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat. Methods 11:817–20 [Google Scholar]
  112. Steinberg KM, Schneider VA, Graves-Lindsay TA, Fulton RS, Agarwala R. 112.  et al. 2014. Single haplotype assembly of the human genome from a hydatidiform mole. Genome Res 24:2066–76 [Google Scholar]
  113. Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A. 113.  et al. 2015. An integrated map of structural variation in 2,504 human genomes. Nature 526:75–81 [Google Scholar]
  114. Szalay T, Golovchenko JA. 114.  2015. De novo sequencing and variant calling with nanopores using PoreSeq. Nat. Biotechnol. 33:1087–91 [Google Scholar]
  115. Tennessen JA, Bigham AW, O'Connor TD, Fu W, Kenny EE. 115.  et al. 2012. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 337:64–69 [Google Scholar]
  116. Tilgner H, Grubert F, Sharon D, Snyder MP. 116.  2014. Defining a personal, allele-specific, and single-molecule long-read transcriptome. PNAS 111:9869–74 [Google Scholar]
  117. Travers KJ, Chin CS, Rank DR, Eid JS, Turner SW. 117.  2010. A flexible and efficient template format for circular consensus sequencing and SNP detection. Nucleic Acids Res 38:e159 [Google Scholar]
  118. Treutlein B, Gokce O, Quake SR, Sudhof TC. 118.  2014. Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing. PNAS 111:E1291–99 [Google Scholar]
  119. Trujillano D, Weiss ME, Koster J, Papachristos EB, Werber M. 119.  et al. 2015. Validation of a semiconductor next-generation sequencing assay for the clinical genetic screening of CFTR. Mol. Genet. Genom. Med. 3:396–403 [Google Scholar]
  120. Uemura S, Aitken CE, Korlach J, Flusberg BA, Turner SW, Puglisi JD. 120.  2010. Real-time tRNA transit on single translating ribosomes at codon resolution. Nature 464:1012–17 [Google Scholar]
  121. Valouev A, Ichikawa J, Tonthat T, Stuart J, Ranade S. 121.  et al. 2008. A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. Genome Res. 18:1051–63 [Google Scholar]
  122. Veltman JA, Brunner HG. 122.  2012. De novo mutations in human genetic disease. Nat. Rev. Genet. 13:565–75 [Google Scholar]
  123. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ. 123.  et al. 2001. The sequence of the human genome. Science 291:1304–51 [Google Scholar]
  124. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr., Kinzler KW. 124.  2013. Cancer genome landscapes. Science 339:1546–58 [Google Scholar]
  125. Wang Y, Yang Q, Wang Z. 125.  2014. The evolution of nanopore sequencing. Front. Genet. 5:449 [Google Scholar]
  126. Warren RL, Yang C, Vandervalk BP, Behsaz B, Lagman A. 126.  et al. 2015. LINKS: scalable, alignment-free scaffolding of draft genomes with long reads. GigaScience 4:35 [Google Scholar]
  127. Watson CT, Steinberg KM, Huddleston J, Warren RL, Malig M. 127.  et al. 2013. Complete haplotype sequence of the human immunoglobulin heavy-chain variable, diversity, and joining genes and characterization of allelic and copy-number variation. Am. J. Hum. Genet. 92:530–46 [Google Scholar]
  128. Watson JD, Crick FH. 128.  1953. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 171:737–38 [Google Scholar]
  129. Westbrook CJ, Karl JA, Wiseman RW, Mate S, Koroleva G. 129.  et al. 2015. No assembly required: full-length MHC class I allele discovery by PacBio circular consensus sequencing. Hum. Immunol. 76:891–96 [Google Scholar]
  130. Wetterstrand K. 130.  2016. DNA sequencing costs: data from the NHGRI Genome Sequencing Program (GSP) http://www.genome.gov/27541954/dna-sequencing-costs-data
  131. Wheeler DA, Wang L. 131.  2013. From human genome to cancer genome: the first decade. Genome Res 23:1054–62 [Google Scholar]
  132. Willig LK, Petrikin JE, Smith LD, Saunders CJ, Thiffault I. 132.  et al. 2015. Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings. Lancet Respir. Med. 3:377–87 [Google Scholar]
  133. Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB. 133.  et al. 2011. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet. Med. 13:255–62 [Google Scholar]
  134. Xu B, Roos JL, Dexheimer P, Boone B, Plummer B. 134.  et al. 2011. Exome sequencing supports a de novo mutational paradigm for schizophrenia. Nat. Genet. 43:864–68 [Google Scholar]
  135. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A. 135.  et al. 2013. Clinical whole-exome sequencing for the diagnosis of Mendelian disorders. N. Engl. J. Med. 369:1502–11 [Google Scholar]
  136. Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA. 136.  et al. 2015. Germline mutations in predisposition genes in pediatric cancer. N. Engl. J. Med. 373:2336–46 [Google Scholar]
  137. Zook JM, Chapman B, Wang J, Mittelman D, Hofmann O. 137.  et al. 2014. Integrating human sequence data sets provides a resource of benchmark SNP and indel genotype calls. Nat. Biotechnol. 32:246–51 [Google Scholar]

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