Application of single-cell genomics in cancer: Promise and challenges

Human Molecular Genetics

Volumn 24, Issue R1, 2015, Pages R74-R84

  Quin, F Will ^a,b   Mead, Adam J ^a,c  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c CHURCHILL HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CANCER GENETICS; CELL INTERACTION; DISEASE COURSE; DNA INTEGRATION; GENE MUTATION; GENETIC HETEROGENEITY; GENOMICS; HUMAN; METASTASIS; NONHUMAN; PRIORITY JOURNAL; REVIEW; SENSITIVITY AND SPECIFICITY; SEQUENCE ANALYSIS; SINGLE CELL ANALYSIS; SYSTEMS BIOLOGY; ANIMAL; GENETICS; NEOPLASMS; PATHOLOGY; PROCEDURES;

ANIMALS; GENOMICS; HUMANS; NEOPLASMS; SENSITIVITY AND SPECIFICITY; SINGLE-CELL ANALYSIS;

EID: 84943799688     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddv235     Document Type: Review

References (112)

1. Stratton, M.R., Campbell, P.J. and Futreal, P.A. (2009) The cancer genome. Nature, 458, 719-724.
2. McGranahan, N. and Swanton, C. (2015) Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell, 27, 15-26.
3. Nowell, P.C. (1976) The clonal evolution of tumor cell populations. Science, 194, 23-28.
4. Yates, L.R. and Campbell, P.J. (2012) Evolution of the cancer genome. Nat. Rev. Genet., 13, 795-806.
5. Ding, L., Wendl, M.C., McMichael, J.F. and Raphael, B.J. (2014) Expanding the computational toolbox for mining cancer genomes. Nat. Rev. Genet., 15, 556-570.
6. Greaves, M. and Maley, C.C. (2012) Clonal evolution in cancer. Nature, 481, 306-313.
7. Van Loo, P. and Voet, T. (2014) Single cell analysis of cancer genomes. Curr. Opin. Genet. Dev., 24, 82-91.
8. Dean, F.B., Hosono, S., Fang, L., Wu, X., Faruqi, A.F., Bray-Ward, P., Sun, Z., Zong, Q., Du, Y., Du, J. et al. (2002) Comprehensive human genome amplification using multiple displacement amplification. Proc. Natl Acad. Sci USA, 99, 5261-5266.
9. Spits, C., Le Caignec, C., De Rycke, M., Van Haute, L., Van Steirteghem, A., Liebaers, I. and Sermon, K. (2006) Wholegenome multiple displacement amplification from single cells. Nat. Protoc., 1, 1965-1970.
10. Zong, C., Lu, S., Chapman, A. and Xie, S. (2012) Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science, 338, 1622-1626.
11. Anderson, K., Lutz, C., van Delft, F.W., Bateman, C.M., Guo, Y., Colman, S.M., Kempski, H., Moorman, A.V., Titley, I., Swansbury, J. et al. (2011) Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature, 469, 356-361.
12. Gole, J., Gore, A., Richards, A., Chiu, Y.J., Fung, H.L., Bushman, D., Chiang, H.I., Chun, J., Lo, Y.H. and Zhang, K. (2013) Massively parallel polymerase cloning and genomesequencing of single cells using nanoliter microwells. Nat. Biotechnol., 31, 1126-1132.
13. Ramskold, D., Luo, S., Wang, Y.C., Li, R., Deng, Q., Faridani, O.R., Daniels, G.A., Khrebtukova, I., Loring, J.F., Laurent, L.C. et al. (2012) Full-length mRNA-Seq fromsingle-cell levels of RNA and individual circulating tumor cells. Nat. Biotechnol., 30, 777-782.
14. Islam, S., Zeisel, A., Joost, S., La Manno, G., Zajac, P., Kasper, M., Lonnerberg, P. and Linnarsson, S. (2014) Quantitative single-cell RNA-seq with unique molecular identifiers. Nat. Methods, 11, 163-166.
15. Kivioja, T., Vaharautio, A., Karlsson, K., Bonke, M., Enge, M., Linnarsson, S. and Taipale, J. (2012) Counting absolute numbers of molecules using unique molecular identifiers. Nat. Methods, 9, 72-74.
16. Hashimshony, T., Wagner, F., Sher, N. and Yanai, I. (2012) CEL-Seq: single-cell RNA-Seq by multiplexed linear amplification. Cell Rep., 2, 666-673.
17. Tang, F., Barbacioru, C., Wang, Y., Nordman, E., Lee, C., Xu, N., Wang, X., Bodeau, J., Tuch, B.B., Siddiqui, A. et al. (2009) mRNA-Seq whole-transcriptome analysis of a single cell. Nat. Methods, 6, 377-382.
18. Pan, X., Durrett, R.E., Zhu, H., Tanaka, Y., Li, Y., Zi, X., Marjani, S.L., Euskirchen, G., Ma, C., Lamotte, R.H. et al. (2013) Two methods for full-length RNA sequencing for low quantities of cells and single cells. Proc. Natl Acad. Sci. USA, 110, 594-599.
19. Wu, A.R., Neff, N.F., Kalisky, T., Dalerba, P., Treutlein, B., Rothenberg, M.E., Mburu, F.M., Mantalas, G.L., Sim, S., Clarke, M.F. et al. (2014) Quantitative assessment of singlecell RNA-sequencing methods. Nat. Methods, 11, 41-46.
20. Macosko, E.Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A.R., Kamitaki, N., Martersteck, E.M. et al. (2015) Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell, 161, 1202-1214.
21. Fan, H.C., Fu, G.K. and Fodor, S.P. (2015) Expression profiling. Combinatorial labeling of single cells for gene expression cytometry. Science, 347, 1258367.
22. Klein, A.M., Mazutis, L., Akartuna, I., Tallapragada, N., Veres, A., Li, V., Peshkin, L., Weitz, D.A. and Kirschner, M.W. (2015) Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell, 161, 1187-1201.
23. Lee, J., Daugharthy, E., Scheiman, J., Kalhor, R., Yang, J., Ferrante, T., Terry, R., Jeanty, S., Li, C., Amamoto, R. et al. (2014) Highly Multiplexed Subcellular RNA Sequencing in Situ. Science, 343, 1360-1363.
24. Achim, K., Pettit, J.-B., Saraiva, L., Gavriouchkina, D., Larsson, T., Arendt, D. and Marioni, J. (2015) High-throughput spatial mapping of single-cell RNA-seq data to tissue of origin. BMC Biotechnol., 33, 503-509.
25. Satija, R., Farrell, J., Gennert, D., Schier, A. and Regev, A. (2015) Spatial reconstruction of single-cell gene expression data. BMC Biotechnol., 33, 495-502.
26. Semrau, S., Crosetto, N., Bienko, M., Boni, M., Bernasconi, P., Chiarle, R. and van Oudenaarden, A. (2014) FuseFISH: robust detection of transcribed gene fusions in single cells. Cell Rep., 6, 18-23.
27. Smallwood, S., Lee, H., Angermueller, C., Krueger, F., Saadeh, H., Peat, J., Andrews, S., Stegle, O., Reik, W. and Kelsey, G. (2014) Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat. Meth., 11, 817-820.
28. Farlik, M., Sheffield, N., Nuzzo, A., Datlinger, P., Schönegger, A., Klughammer, J. and Bock, C. (2015) Single-cell DNA methylome sequencing and bioinformatic inference of epigenomic cell-state dynamics. Cell Rep., 10, 1386-1397.
29. Cusanovich, D., Daza, R., Adey, A., Pliner, H., Christiansen, L., Gunderson, K., Steemers, F., Trapnell, C. and Shendure, J. (2015) Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing. Science, 348, 910-914.
30. Nagano, T., Lubling, Y., Stevens, T.J., Schoenfelder, S., Yaffe, E., Dean, W., Laue, E.D., Tanay, A. and Fraser, P. (2013) Singlecell Hi-C reveals cell-to-cell variability in chromosome structure. Nature, 502, 59-64.
31. Zunder, E., Finck, R., Behbehani, G., Amir, E.-A., Krishnaswamy, S., Gonzalez, V., Lorang, C., Bjornson, Z., Spitzer, M., Bodenmiller, B. et al. (2015) Palladium-basedmass tag cell barcodingwith a doublet-filtering scheme and single-cell deconvolution algorithm. Nat. Protocol., 10, 316-333.
32. Giesen, C., Wang, H., Schapiro, D., Zivanovic, N., Jacobs, A., Hattendorf, B., Schuffler, P., Grolimund, D., Buhmann, J., Brandt, S. et al. (2014) Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat. Meth., 11, 417-422.
33. Hoppe, P.S., Coutu, D.L. and Schroeder, T. (2014) Single-cell technologies sharpen up mammalian stem cell research. Nat. Cell Biol., 16, 919-927.
34. Gawad, C., Koh, W. and Quake, S. (2014) Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics. Proc. Natl Acad. Sci., 111, 17947-17952.
35. Campbell, P.J., Yachida, S., Mudie, L.J., Stephens, P.J., Pleasance, E.D., Stebbings, L.A., Morsberger, L.A., Latimer, C., McLaren, S., Lin, M.L. et al. (2010) The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature, 467, 1109-1113.
36. Ortmann, C.A., Kent, D.G., Nangalia, J., Silber, Y., Wedge, D.C., Grinfeld, J., Baxter, E.J., Massie, C.E., Papaemmanuil, E., Menon, S. et al. (2015) Effect of mutation order on myeloproliferative neoplasms. N. Engl. J. Med., 372, 601-612.
37. Kantarjian, H. and Zwelling, L. (2013) Cancer drug prices and the free-market forces. Cancer, 119, 3903-3905.
38. Navin, N., Kendall, J., Troge, J., Andrews, P., Rodgers, L., McIndoo, J., Cook, K., Stepansky, A., Levy, D., Esposito, D. et al. (2011) Tumour evolution inferred by single-cell sequencing. Nature, 472, 90-94.
39. Wang, Y., Waters, J., Leung, M., Unruh, A., Roh, W., Shi, X., Chen, K., Scheet, P., Vattathil, S., Liang, H. et al. (2014) Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature, 512, 155-160.
40. Eirew, P., Steif, A., Khattra, J., Ha, G., Yap, D., Farahani, H., Gelmon, K., Chia, S., Mar, C., Wan, A. et al. (2015) Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution. Nature, 518, 422-426.
41. Voet, T., Kumar, P., Van Loo, P., Cooke, S.L., Marshall, J., Lin, M.L., Zamani Esteki, M., Van der Aa, N., Mateiu, L., McBride, D.J. et al. (2013) Single-cell paired-end genome sequencing reveals structural variation per cell cycle. Nucleic Acids Res., 41, 6119-6138.
42. Hou, Y., Song, L., Zhu, P., Zhang, B., Tao, Y., Xu, X., Li, F., Wu, K., Liang, J., Shao, D. et al. (2012) Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm. Cell, 148, 873-885.
43. Xu, X., Hou, Y., Yin, X., Bao, L., Tang, A., Song, L., Li, F., Tsang, S., Wu, K., Wu, H. et al. (2012) Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor. Cell, 148, 886-895.
44. Li, Y., Xu, X., Song, L., Hou, Y., Li, Z., Tsang, S., Li, F., Im, K., Wu, K., Wu, H. et al. (2012) Single-cell sequencing analysischaracterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer. GigaScience, 1, 12.
45. Yu, C., Yu, J., Yao, X., Wu, W., Lu, Y., Tang, S., Li, X., Bao, L., Li, X., Hou, Y. et al. (2014) Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing. Cell Res., 24, 701-712.
46. Heitzer, E., Auer, M., Gasch, C., Pichler, M., Ulz, P., Hoffmann, E.M., Lax, S., Waldispuehl-Geigl, J., Mauermann, O., Lackner, C. et al. (2013) Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cell Res., 73, 2965-2975.
47. Hughes, A., Magrini, V., Demeter, R., Miller, C., Fulton, R., Fulton, L., Eades, W., Elliott, K., Heath, S., Westervelt, P. et al. (2014) Clonal architecture of secondary acute myeloid leukemia defined by single-cell sequencing. PLoS Genet., 10, e1004462.
48. Lohr, J., Adalsteinsson, V., Cibulskis, K., Choudhury, A., Rosenberg, M., Cruz-Gordillo, P., Francis, J., Zhang, C.-Z., Shalek, A., Satija, R. et al. (2014) Whole-exome sequencing of circulating tumor cells provides a windowinto metastatic prostate cancer. Nat. Biotech., 32, 479-484.
49. Ni, X., Zhuo, M., Su, Z., Duan, J., Gao, Y., Wang, Z., Zong, C., Bai, H., Chapman, A., Zhao, J. et al. (2013) Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proc. Natl Acad. Sci. USA, 110, 21083-21088.
50. Swennenhuis, J.F., Reumers, J., Thys, K., Aerssens, J. and Terstappen, L.W. (2013) Efficiency of whole genome amplification of single circulating tumor cells enriched by Cell-Search and sorted by FACS. Genome Med., 5, 106.
51. Shapiro, E., Biezuner, T. and Linnarsson, S. (2013) Single-cell sequencing-based technologies will revolutionize wholeorganism science. Nat. Rev. Genet., 14, 618-630.
52. Guo, H., Zhu, P., Wu, X., Li, X., Wen, L. and Tang, F. (2013) Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing. Genome Res., 23, 2126-2135.
53. Lorthongpanich, C., Cheow, L.F., Balu, S., Quake, S.R., Knowles, B.B., Burkholder, W.F., Solter, D. and Messerschmidt, D.M. (2013) Single-cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos. Science, 341, 1110-1112.
54. Bendall, S.C. and Nolan, G.P. (2012) From single cells to deep phenotypes in cancer. Nat. Biotechnol., 30, 639-647.
55. Plaks, V., Kong, N. and Werb, Z. (2015) The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell, 16, 225-238.
56. Treutlein, B., Brownfield, D.G., Wu, A.R., Neff, N.F., Mantalas, G.L., Espinoza, F.H., Desai, T.J., Krasnow, M.A. and Quake, S. R. (2014) Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. Nature, 509, 371-375.
57. Wen, L. and Tang, F. (2014) Reconstructing complex tissues from single-cell analyses. Cell, 157, 771-773.
58. Durruthy-Durruthy, R., Gottlieb, A., Hartman, B.H., Waldhaus, J., Laske, R.D., Altman, R. and Heller, S. (2014) Reconstruction of the mouse otocyst and early neuroblast lineage at singlecell resolution. Cell, 157, 964-978.
59. Xue, Z., Huang, K., Cai, C., Cai, L., Jiang, C.Y., Feng, Y., Liu, Z., Zeng, Q., Cheng, L., Sun, Y.E. et al. (2013) Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing. Nature, 500, 593-597.
60. Yan, L., Yang, M., Guo, H., Yang, L., Wu, J., Li, R., Liu, P., Lian, Y., Zheng, X., Yan, J. et al. (2013) Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells. Nat. Struct. Mol. Biol., 20, 1131-1139.
61. Shalek, A.K., Satija, R., Adiconis, X., Gertner, R.S., Gaublomme, J.T., Raychowdhury, R., Schwartz, S., Yosef, N., Malboeuf, C., Lu, D. et al. (2013) Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells. Nature, 498, 236-240.
62. Ting, D., Wittner, B., Ligorio, M., Vincent Jordan, N., Shah, A., Miyamoto, D., Aceto, N., Bersani, F., Brannigan, B., Xega, K. et al. (2015) Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Rep., 8, 1905-1918.
63. Dalerba, P., Kalisky, T., Sahoo, D., Rajendran, P.S., Rothenberg, M.E., Leyrat, A.A., Sim, S., Okamoto, J., Johnston, D.M., Qian, D. et al. (2011) Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat. Biotechnol., 29, 1120-1127.
64. Patel, A., Tirosh, I., Trombetta, J., Shalek, A., Gillespie, S., Wakimoto, H., Cahill, D., Nahed, B., Curry, W., Martuza, R. et al. (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science, 344, 1396-1401.
65. Lee, M.-C., Lopez-Diaz, F., Khan, S., Tariq, M., Dayn, Y., Vaske, C., Radenbaugh, A., Kim, H., Emerson, B. and Pourmand, N. (2014) Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing. Proc. Natl Acad. Sci. USA, 111, E4726-E4735.
66. Bheda, P. and Schneider, R. (2014) Epigenetics reloaded: the single-cell revolution. Trends Cell Biol., 24, 712-723.
67. Magee, J.A., Piskounova, E. and Morrison, S.J. (2012) Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell, 21, 283-296.
68. Woll, P.S., Kjallquist, U., Chowdhury, O., Doolittle, H., Wedge, D.C., Thongjuea, S., Erlandsson, R., Ngara, M., Anderson, K., Deng, Q. et al. (2014) Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer Cell, 25, 794-808.
69. Tehranchi, R., Woll, P.S., Anderson, K., Buza-Vidas, N., Mizukami, T., Mead, A.J., Astrand-Grundstrom, I., Strombeck, B., Horvat, A., Ferry, H. et al. (2010) Persistent malignant stem cells in del(5q) myelodysplasia in remission. N. Engl J. Med., 363, 1025-1037.
70. Jan, M., Snyder, T., Corces-Zimmerman, R., Vyas, P., Weissman, I., Quake, S. and Majeti, R. (2012) Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Sci. Transl. Med., 4, 149ra118-149ra118.
71. Genovese, G., Kahler, A.K., Handsaker, R.E., Lindberg, J., Rose, S.A., Bakhoum, S.F., Chambert, K., Mick, E., Neale, B. M., Fromer, M. et al. (2014) Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N. Engl. J. Med., 371, 2477-2487.
72. Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P.V., Mar, B.G., Lindsley, R.C., Mermel, C.H., Burtt, N., Chavez, A. et al. (2014) Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med., 371, 2488-2498.
73. Busque, L., Patel, J.P., Figueroa, M.E., Vasanthakumar, A., Provost, S., Hamilou, Z., Mollica, L., Li, J., Viale, A., Heguy, A. et al. (2012) Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat. Genet., 44, 1179-1181.
74. Baslan, T., Kendall, J., Rodgers, L., Cox, H., Riggs, M., Stepansky, A., Troge, J., Ravi, K., Esposito, D., Lakshmi, B. et al. (2012) Genome-wide copy number analysis of single cells. Nat. Protoc., 7, 1024-1041.
75. Crasta, K., Ganem, N.J., Dagher, R., Lantermann, A.B., Ivanova, E.V., Pan, Y., Nezi, L., Protopopov, A., Chowdhury, D. and Pellman, D. (2012) DNA breaks and chromosome pulverization from errors in mitosis. Nature, 482, 53-58.
76. Chaudhuri, P.K., Ebrahimi Warkiani, M., Jing, T., Kenry and Lim, C.T. (2015) Microfluidics for research and applications in oncology. Analyst, in press.
77. Qian, W., Zhang, Y. and Chen, W. (2015) Capturing cancer: emerging microfluidic technologies for the capture and characterization of circulating tumor cells. Small, in press.
78. Sanjuan-Pla, A., Macaulay, I.C., Jensen, C.T., Woll, P.S., Luis, T.C., Mead, A., Moore, S., Carella, C., Matsuoka, S., Bouriez Jones, T. et al. (2013) Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy. Nature, 502, 232-236.
79. de Bruin, E.C., McGranahan, N., Mitter, R., Salm, M., Wedge, D.C., Yates, L., Jamal-Hanjani, M., Shafi, S., Murugaesu, N., Rowan, A.J. et al. (2014) Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science, 346, 251-256.
80. Gerlinger, M., Horswell, S., Larkin, J., Rowan, A.J., Salm, M.P., Varela, I., Fisher, R., McGranahan, N., Matthews, N., Santos, C.R. et al. (2014) Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nat. Genet., 46, 225-233.
81. Walter, M.J., Shen, D., Ding, L., Shao, J., Koboldt, D.C., Chen, K., Larson, D.E., McLellan, M.D., Dooling, D., Abbott, R. et al. (2012) Clonal architecture of secondary acute myeloid leukemia. N. Engl. J. Med., 366, 1090-1098.
82. Schepers, K., Campbell, T.B. and Passegue, E. (2015) Normal and leukemic stem cell niches: insights and therapeutic opportunities. Cell Stem Cell, 16, 254-267.
83. Frumkin, D., Wasserstrom, A., Itzkovitz, S., Harmelin, A., Rechavi, G. and Shapiro, E. (2008) Amplification of multiple genomic loci fromsingle cells isolated by laser micro-dissection of tissues. BMC Biotechnol., 8, 17.
84. Ding, L., Ley, T.J., Larson, D.E., Miller, C.A., Koboldt, D.C., Welch, J.S., Ritchey, J.K., Young, M.A., Lamprecht, T., McLellan, M.D. et al. (2012) Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature, 481, 506-510.
85. Mullighan, C.G., Phillips, L.A., Su, X., Ma, J., Miller, C.B., Shurtleff, S.A. and Downing, J.R. (2008) Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science, 322, 1377-1380.
86. Alix-Panabieres, C. and Pantel, K. (2013) Circulating tumor cells: liquid biopsy of cancer. Clin. Chem., 59, 110-118.
87. Lasken, R. (2013) Single-cell sequencing in its prime. Nat. Biotech., 31, 211-212.
88. Macaulay, I. and Voet, T. (2014) Single cell genomics: advances and future perspectives. PLoS Genet., 10, e1004126.
89. Lauri, A., Lazzari, G., Galli, C., Lagutina, I., Genzini, E., Braga, F., Mariani, P. andWilliams, J. (2013) Assessment of MDA efficiency for genotyping using cloned embryo biopsies. Genomics, 101, 24-29.
90. de Bourcy, C.F., De Vlaminck, I., Kanbar, J.N., Wang, J., Gawad, C. and Quake, S.R. (2014) A quantitative comparison of single-cell whole genome amplification methods. PloS One, 9, e105585.
91. Fan, H.C., Wang, J., Potanina, A. and Quake, S.R. (2011) Whole-genome molecular haplotyping of single cells. Nat. Biotechnol., 29, 51-57.
92. Lecault, V., White, A.K., Singhal, A. and Hansen, C.L. (2012) Microfluidic single cell analysis: from promise to practice. Curr. Opin. Chem. Biol., 16, 381-390.
93. Streets, A.M., Zhang, X., Cao, C., Pang, Y., Wu, X., Xiong, L., Yang, L., Fu, Y., Zhao, L., Tang, F. et al. (2014) Microfluidic single-cell whole-transcriptome sequencing. Proc. Natl Acad. Sci. USA, 111, 7048-7053.
94. Wang, J., Fan, H.C., Behr, B. and Quake, S.R. (2012) Genomewide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell, 150, 402-412.
95. Potter, N.E., Ermini, L., Papaemmanuil, E., Cazzaniga, G., Vijayaraghavan, G., Titley, I., Ford, A., Campbell, P., Kearney, L. and Greaves, M. (2013) Single-cell mutational profiling and clonal phylogeny in cancer. Genome Res., 23, 2115-2125.
96. Brennecke, P., Anders, S., Kim, J.K., Kolodziejczyk, A.A., Zhang, X., Proserpio, V., Baying, B., Benes, V., Teichmann, S.A., Marioni, J.C. et al. (2013) Accounting for technical noise in single-cell RNA-seq experiments. Nat. Methods, 10, 1093-1095.
97. Buettner, F., Natarajan, K., Casale, P., Proserpio, V., Scialdone, A., Theis, F., Teichmann, S., Marioni, J. and Stegle, O. (2015) Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells. Nat. Biotechnol., 33, 155-160.
98. Nakamura-Ishizu, A., Takizawa, H. and Suda, T. (2014) The analysis, roles and regulation of quiescence in hematopoietic stem cells. Development, 141, 4656-4666.
99. Talari, A.C.S., Evans, C.A., Holen, I., Coleman, R.E. and Rehman, I. (2015) Raman spectroscopic analysis differentiates between breast cancer cell lines. J. Raman Spectrosc., 46, 421-427.
100. Klein, C.A., Seidl, S., Petat-Dutter, K., Offner, S., Geigl, J.B., Schmidt-Kittler, O., Wendler, N., Passlick, B., Huber, R.M., Schlimok, G. et al. (2002) Combined transcriptome and genome analysis of single micrometastatic cells. Nat. Biotechnol., 20, 387-392.
101. Dey, S., Kester, L., Spanjaard, B., Bienko, M. and van Oudenaarden, A. (2015) Integrated genome and transcriptome sequencing of the same cell. Nat. Biotech., 33, 285-289.
102. Li, W., Calder, B., Mar, J. and Vijg, J. (2015) Single-cell transcriptogenomics reveals transcriptional exclusion of ENU-mutated alleles. Mutat. Res. Fund. Mol. Mech. Muta., 772, 55-62.
103. Macaulay, I., Haerty, W., Kumar, P., Li, Y., Hu, T., Teng, M., Goolam, M., Saurat, N., Coupland, P., Shirley, L. et al. (2015) G&T-seq: parallel sequencing of single-cell genomes and transcriptomes. Nat. Meth., 12, 519-522.
104. Wilson, N.K., Kent, D.G., Buettner, F., Shehata, M., Macaulay, I.C., Calero-Nieto, F.J., Sanchez Castillo, M., Oedekoven, C.A., Diamanti, E., Schulte, R. et al. (2015) Combined singlecell functional and gene expression analysis resolves heterogeneity within stem cell populations. Cell Stem Cell, 16, 712-724.
105. Yamamoto, R., Morita, Y., Ooehara, J., Hamanaka, S., Onodera, M., Rudolph, K.L., Ema, H. and Nakauchi, H. (2013) Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell, 154, 1112-1126.
106. Amir, E.-a., Davis, K., Tadmor, M., Simonds, E., Levine, J., Bendall, S., Shenfeld, D., Krishnaswamy, S., Nolan, G. and Pe'er, D. (2013) viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat. Biotech., 31, 545-552.
107. Marco, E., Karp, R., Guo, G., Robson, P., Hart, A., Trippa, L. and Yuan, G.-C. (2014) Bifurcation analysis of single-cell gene expression data reveals epigenetic landscape. Proc. Natl Acad. Sci., 111, E5643-E5650.108. Pollen, A., Nowakowski, T., Shuga, J., Wang, X., Leyrat, A., Lui, J., Li, N., Szpankowski, L., Fowler, B., Chen, P. et al. (2014) Lowcoverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex. Nat. Biotechnol., 32, 1053-1058.
108. Pollen, A., Nowakowski, T., Shuga, J., Wang, X., Leyrat, A., Lui, J., Li, N., Szpankowski, L., Fowler, B., Chen, P. et al. (2014) Lowcoverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex. Nat. Biotechnol., 32, 1053-1058.
109. Bendall, S., Davis, K., Amir, E.-A.D., Tadmor, M., Simonds, E., Chen, T., Shenfeld, D., Nolan, G. and Pe'er, D. (2014) Singlecell trajectory detection uncovers progression and regulatory coordination in human B cell development. Cell, 157, 714-725.
110. Dar, R., Hosmane, N., Arkin, M., Siliciano, R. andWeinberger, L. (2014) Screening for noise in gene expression identifies drug synergies. Science, 344, 1392-1396.
111. Kiviet, D., Nghe, P., Walker, N., Boulineau, S., Sunderlikova, V. and Tans, S. (2014) Stochasticity of metabolism and growth at the single-cell level. Nature, 514, 376-379.
112. Wills, Q.F., Livak, K.J., Tipping, A.J., Enver, T., Goldson, A.J., Sexton, D.W. and Holmes, C. (2013) Single-cell gene expression analysis reveals genetic associations masked in wholetissue experiments. Nat. Biotechnol., 31, 748-752.