1932

Abstract

We present a survey of single-cell whole-genome amplification (WGA) methods, including degenerate oligonucleotide–primed polymerase chain reaction (DOP-PCR), multiple displacement amplification (MDA), and multiple annealing and looping–based amplification cycles (MALBAC). The key parameters to characterize the performance of these methods are defined, including genome coverage, uniformity, reproducibility, unmappable rates, chimera rates, allele dropout rates, false positive rates for calling single-nucleotide variations, and ability to call copy-number variations. Using these parameters, we compare five commercial WGA kits by performing deep sequencing of multiple single cells. We also discuss several major applications of single-cell genomics, including studies of whole-genome de novo mutation rates, the early evolution of cancer genomes, circulating tumor cells (CTCs), meiotic recombination of germ cells, preimplantation genetic diagnosis (PGD), and preimplantation genomic screening (PGS) for in vitro–fertilized embryos.

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/content/journals/10.1146/annurev-genom-090413-025352
2015-08-24
2024-03-29
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Literature Cited

  1. 1. 1000 Genomes Proj. Consort 2010. A map of human genome variation from population-scale sequencing. Nature 467:1061–73 [Google Scholar]
  2. Bansal V, Tewhey R, Topol EJ, Schork NJ. 2.  2011. The next phase in human genetics. Nat. Biotechnol. 29:38–39 [Google Scholar]
  3. Barrett MT, Reid BJ, Joslyn G. 3.  1995. Genotypic analysis of multiple loci in somatic cells by whole genome amplification. Nucleic Acids Res. 23:3488–92 [Google Scholar]
  4. Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J. 4.  et al. 2008. Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456:53–59 [Google Scholar]
  5. Blanco L, Bernad A, Lázaro JM, Martin G, Garmendia C, Salas M. 5.  1989. Highly efficient DNA synthesis by the phage ϕ29 DNA polymerase: symmetrical mode of DNA replication. J. Biol. Chem. 264:8935–40 [Google Scholar]
  6. Chapman AR, He Z, Lu S, Yong J, Tan L. 6.  et al. 2015. Single cell transcriptome amplification with MALBAC. PLOS ONE 10:e0120889 [Google Scholar]
  7. Cheung VG, Nelson SF. 7.  1996. Whole genome amplification using a degenerate oligonucleotide primer allows hundreds of genotypes to be performed on less than one nanogram of genomic DNA. PNAS 93:14676–79 [Google Scholar]
  8. Coop G, Przeworski M. 8.  2007. An evolutionary view of human recombination. Nat. Rev. Genet. 8:23–34 [Google Scholar]
  9. Dago AE, Stepansky A, Carlsson A, Luttgen M, Kendall J. 9.  et al. 2014. Rapid phenotypic and genomic change in response to therapeutic pressure in prostate cancer inferred by high content analysis of single circulating tumor cells. PLOS ONE 9:e101777 [Google Scholar]
  10. Daina G, Ramos L, Obradors A, Rius M, Martinez-Pasarell O. 10.  et al. 2013. First successful double-factor PGD for Lynch syndrome: monogenic analysis and comprehensive aneuploidy screening. Clin. Genet. 84:70–73 [Google Scholar]
  11. de Bourcy CF, De Vlaminck I, Kanbar JN, Wang J, Gawad C, Quake SR. 11.  2014. A quantitative comparison of single-cell whole genome amplification methods. PLOS ONE 9:e105585 [Google Scholar]
  12. Dean FB, Nelson JR, Giesler TL, Lasken RS. 12.  2001. Rapid amplification of plasmid and phage DNA using phi29 DNA polymerase and multiply-primed rolling circle amplification. Genome Res. 11:1095–99 [Google Scholar]
  13. Epstein CJ. 13.  2007. The Consequences of Chromosome Imbalance: Principles, Mechanisms, and Models Cambridge, UK: Cambridge Univ. Press
  14. Fan HC, Wang J, Potanina A, Quake SR. 14.  2011. Whole-genome molecular haplotyping of single cells. Nat. Biotechnol. 29:51–57 [Google Scholar]
  15. Francis JM, Zhang CZ, Maire CL, Jung J, Manzo VE. 15.  et al. 2014. EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov. 4:956–971 [Google Scholar]
  16. Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL. 16.  et al. 2007. A second generation human haplotype map of over 3.1 million SNPs. Nature 449:851–61 [Google Scholar]
  17. Garmendia C, Bernad A, Esteban JA, Blanco L, Salas M. 17.  1992. The bacteriophage ϕ29 DNA polymerase, a proofreading enzyme. J. Biol. Chem. 267:2594–99 [Google Scholar]
  18. Gawad C, Koh W, Quake SR. 18.  2014. Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics. PNAS 111:17947–52 [Google Scholar]
  19. Guo H, Zhu P, Wu X, Li X, Wen L, Tang F. 19.  2013. Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing. Genome Res 23:2126–35 [Google Scholar]
  20. Harris TD, Buzby PR, Babcock H, Beer E, Bowers J. 20.  et al. 2008. Single-molecule DNA sequencing of a viral genome. Science 320:106–9 [Google Scholar]
  21. Hastings PJ, Lupski JR, Rosenberg SM, Ira G. 21.  2009. Mechanisms of change in gene copy number. Nat. Rev. Genet. 10:551–64 [Google Scholar]
  22. Heger M. 22.  2014. Peking University reports first success in trial of single-cell sequencing for PGD. GenomeWeb Oct. 1. http://www.genomeweb.com/sequencing/peking-university-reports-first-success-trial-single-cell-sequencing-pgd
  23. Hinch AG, Tandon A, Patterson N, Song Y, Rohland N. 23.  et al. 2011. The landscape of recombination in African Americans. Nature 476:170–75 [Google Scholar]
  24. Hou Y, Fan W, Yan L, Li R, Lian Y. 24.  et al. 2013. Genome analyses of single human oocytes. Cell 155:1492–506 [Google Scholar]
  25. Hou Y, Song L, Zhu P, Zhang B, Tao Y. 25.  et al. 2012. Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm. Cell 148:873–85 [Google Scholar]
  26. Huang J, Yan L, Fan W, Zhao N, Zhang Y. 26.  et al. 2014. Validation of multiple annealing and looping-based amplification cycle sequencing for 24-chromosome aneuploidy screening of cleavage-stage embryos. Fertil. Steril. 102:1685–91 [Google Scholar]
  27. Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK. 27.  et al. 2004. Detection of large-scale variation in the human genome. Nat. Genet. 36:949–51 [Google Scholar]
  28. Ingles J, Doolan A, Chiu C, Seidman J, Seidman C, Semsarian C. 28.  2005. Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling. J. Med. Genet. 42:e59 [Google Scholar]
  29. 29. Int. HapMap Consort 2005. A haplotype map of the human genome. Nature 437:1299–320 [Google Scholar]
  30. Jeffreys AJ, Neumann R. 30.  2002. Reciprocal crossover asymmetry and meiotic drive in a human recombination hot spot. Nat. Genet. 31:267–71 [Google Scholar]
  31. Kalisky T, Quake SR. 31.  2011. Single-cell genomics. Nat. Methods 8:311–14 [Google Scholar]
  32. Kirkness EF, Grindberg RV, Yee-Greenbaum J, Marshall CR, Scherer SW. 32.  et al. 2013. Sequencing of isolated sperm cells for direct haplotyping of a human genome. Genome Res. 23:826–32 [Google Scholar]
  33. Kitzman JO, MacKenzie AP, Adey A, Hiatt JB, Patwardhan RP. 33.  et al. 2011. Haplotype-resolved genome sequencing of a Gujarati Indian individual. Nat. Biotechnol. 29:59–63 [Google Scholar]
  34. Kong A, Thorleifsson G, Gudbjartsson DF, Masson G, Sigurdsson A. 34.  et al. 2010. Fine-scale recombination rate differences between sexes, populations and individuals. Nature 467:1099–103 [Google Scholar]
  35. Lasken RS. 35.  2012. Genomic sequencing of uncultured microorganisms from single cells. Nat. Rev. Microbiol. 10:631–40 [Google Scholar]
  36. Lasken RS. 36.  2013. Single-cell sequencing in its prime. Nat. Biotechnol. 31:211–12 [Google Scholar]
  37. Lasken RS, Egholm M. 37.  2003. Whole genome amplification: abundant supplies of DNA from precious samples or clinical specimens. Trends Biotechnol. 21:531–35 [Google Scholar]
  38. Levy S, Sutton G, Ng PC, Feuk L, Halpern AL. 38.  et al. 2007. The diploid genome sequence of an individual human. PLOS Biol. 5:e254 [Google Scholar]
  39. Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M. 39.  et al. 2014. Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat. Biotechnol. 32:479–84 [Google Scholar]
  40. Lu S, Zong C, Fan W, Yang M, Li J. 40.  et al. 2012. Probing meiotic recombination and aneuploidy of single sperm cells by whole-genome sequencing. Science 338:1627–30 [Google Scholar]
  41. Ma L, Xiao Y, Huang H, Wang Q, Rao W. 41.  et al. 2010. Direct determination of molecular haplotypes by chromosome microdissection. Nat. Methods 7:299 [Google Scholar]
  42. MacArthur D. 42.  2012. Methods: face up to false positives. Nature 487:427–28 [Google Scholar]
  43. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS. 43.  et al. 2005. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437:376–80 [Google Scholar]
  44. Morley M, Molony CM, Weber TM, Devlin JL, Ewens KG. 44.  et al. 2004. Genetic analysis of genome-wide variation in human gene expression. Nature 430:743–47 [Google Scholar]
  45. Mueller E, Brueck C. 45.  2015. Whole genome amplification for single cell biology Tech. Doc., Sigma-Aldrich, St. Louis, MO. http://www.sigmaaldrich.com/technical-documents/articles/life-science-innovations/whole-genome-amplification.html
  46. 46. Nat. Methods Eds 2014. Method of the Year 2013. Nat. Methods 11:1 [Google Scholar]
  47. Navin NE. 47.  2014. Cancer genomics: one cell at a time. Genome Biol. 15:452 [Google Scholar]
  48. Navin NE, Kendall J, Troge J, Andrews P, Rodgers L. 48.  et al. 2011. Tumour evolution inferred by single-cell sequencing. Nature 472:90–94 [Google Scholar]
  49. Ni X, Zhuo M, Su Z, Duan J, Gao Y. 49.  et al. 2013. Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. PNAS 110:21083–88 [Google Scholar]
  50. Peters BA, Kermani BG, Sparks AB, Alferov O, Hong P. 50.  et al. 2012. Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells. Nature 487:190–95 [Google Scholar]
  51. Pugh TJ, Delaney AD, Farnoud N, Flibotte S, Griffith M. 51.  et al. 2008. Impact of whole genome amplification on analysis of copy number variants. Nucleic Acids Res. 36:e80 [Google Scholar]
  52. Rubio C, Rodrigo L, Mir P, Mateu E, Peinado V. 52.  et al. 2013. Use of array comparative genomic hybridization (array-CGH) for embryo assessment: clinical results. Fertil. Steril. 99:1044–48 [Google Scholar]
  53. Ruiz C, Li J, Luttgen MS, Kolatkar A, Kendall JT. 53.  et al. 2015. Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients. Phys. Biol. 12:016008 [Google Scholar]
  54. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R. 54.  et al. 1988. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–91 [Google Scholar]
  55. Sandberg R. 55.  2014. Entering the era of single-cell transcriptomics in biology and medicine. Nat. Methods 11:22–24 [Google Scholar]
  56. Sebat J, Lakshmi B, Troge J, Alexander J, Young J. 56.  et al. 2004. Large-scale copy number polymorphism in the human genome. Science 305:525–28 [Google Scholar]
  57. Shapiro E, Biezuner T, Linnarsson S. 57.  2013. Single-cell sequencing-based technologies will revolutionize whole-organism science. Nat. Rev. Genet. 14:619–30 [Google Scholar]
  58. Shen J, Cram DS, Wu W, Cai L, Yang X. 58.  et al. 2013. Successful PGD for late infantile neuronal ceroid lipofuscinosis achieved by combined chromosome and TPP1 gene analysis. Reprod. BioMed. Online 27:176–83 [Google Scholar]
  59. Suk EK, McEwen GK, Duitama J, Nowick K, Schulz S. 59.  et al. 2011. A comprehensively molecular haplotype-resolved genome of a European individual. Genome Res. 21:1672–85 [Google Scholar]
  60. Tang F, Lao K, Surani MA. 60.  2011. Development and applications of single-cell transcriptome analysis. Nat. Methods 8:Suppl.S6–11 [Google Scholar]
  61. Telenius H, Carter NP, Bebb CE, Nordenskjo M, Ponder BA, Tunnacliffe A. 61.  1992. Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. Genomics 13:718–25 [Google Scholar]
  62. Tewhey R, Bansal V, Torkamani A, Topol EJ, Schork NJ. 62.  2011. The importance of phase information for human genomics. Nat. Rev. Genet. 12:215–23 [Google Scholar]
  63. Tobler KJ, Brezina PR, Benner AT, Du L, Xu X, Kearns WG. 63.  2014. Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates. J. Assist. Reprod. Genet. 31:843–50 [Google Scholar]
  64. Treff NR, Fedick A, Tao X, Devkota B, Taylor D, Scott RT. 64.  2013. Evaluation of targeted next-generation sequencing–based preimplantation genetic diagnosis of monogenic disease. Fertil. Steril. 99:1377–84 [Google Scholar]
  65. Treff NR, Tao X, Ferry KM, Su J, Taylor D, Scott RT. 65.  2012. Development and validation of an accurate quantitative real-time polymerase chain reaction–based assay for human blastocyst comprehensive chromosomal aneuploidy screening. Fertil. Steril. 97:819–24 [Google Scholar]
  66. Van Driest SL, Vasile VC, Ommen SR, Will ML, Tajik AJ. 66.  et al. 2004. Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 44:1903–10 [Google Scholar]
  67. Vogelstein B, Kinzler KW. 67.  2004. Cancer genes and the pathways they control. Nat. Med. 10:789–99 [Google Scholar]
  68. Wang J, Fan HC, Behr B, Quake SR. 68.  2012. Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell 150:402–12 [Google Scholar]
  69. Wang J, Wang W, Li R, Li Y, Tian G. 69.  et al. 2008. The diploid genome sequence of an Asian individual. Nature 456:60–65 [Google Scholar]
  70. Wang Y, Waters J, Leung ML, Unruh A, Roh W. 70.  et al. 2014. Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature 512:155–60 [Google Scholar]
  71. Wells D, Kaur K, Grifo J, Glassner M, Taylor JC. 71.  et al. 2014. Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation. J. Med. Genet. 51:553–62 [Google Scholar]
  72. Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L. 72.  et al. 2008. The complete genome of an individual by massively parallel DNA sequencing. Nature 452:872–76 [Google Scholar]
  73. Xu X, Hou Y, Yin X, Bao L, Tang A. 73.  et al. 2012. Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor. Cell 148:886–95 [Google Scholar]
  74. Yang H, Chen X, Wong WH. 74.  2011. Completely phased genome sequencing through chromosome sorting. PNAS 108:12–17 [Google Scholar]
  75. Yu C, Yu J, Yao X, Wu WK, Lu Y. 75.  et al. 2014. Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing. Cell Res. 24:701–12 [Google Scholar]
  76. Zhang K, Zhu J, Shendure J, Porreca GJ, Aach JD. 76.  et al. 2006. Long-range polony haplotyping of individual human chromosome molecules. Nat. Genet. 38:382–87 [Google Scholar]
  77. Zhang L, Cui X, Schmitt K, Hubert R, Navidi W, Arnheim N. 77.  1992. Whole genome amplification from a single cell: implications for genetic analysis. PNAS 89:5847–51 [Google Scholar]
  78. Zong C, Lu S, Chapman AR, Xie XS. 78.  2012. Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 338:1622–26 [Google Scholar]
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