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Towards error-free profiling of immune repertoires

Abstract

Deep profiling of antibody and T cell–receptor repertoires by means of high-throughput sequencing has become an attractive approach for adaptive immunity studies, but its power is substantially compromised by the accumulation of PCR and sequencing errors. Here we report MIGEC (molecular identifier groups–based error correction), a strategy for high-throughput sequencing data analysis. MIGEC allows for nearly absolute error correction while fully preserving the natural diversity of complex immune repertoires.

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Figure 1: MIGEC analysis.
Figure 2: MIGEC analysis for control clones.

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References

  1. Robins, H.S. et al. Blood 114, 4099–4107 (2009).

    CAS  Article  Google Scholar 

  2. Warren, R.L. et al. Genome Res. 21, 790–797 (2011).

    CAS  Article  Google Scholar 

  3. Venturi, V. et al. J. Immunol. 186, 4285–4294 (2011).

    CAS  Article  Google Scholar 

  4. Mamedov, I.Z. et al. EMBO Mol. Med. 3, 201–207 (2011).

    CAS  Article  Google Scholar 

  5. Klarenbeek, P.L. et al. PLoS Pathog. 8, e1002889 (2012).

    CAS  Article  Google Scholar 

  6. Britanova, O.V. et al. Bone Marrow Transplant. 47, 1479–1481 (2012).

    CAS  Article  Google Scholar 

  7. Bashford-Rogers, R.J. et al. Genome Res. 23, 1874–1884 (2013).

    CAS  Article  Google Scholar 

  8. Putintseva, E.V. et al. Front. Immunol. 4, 463 (2013).

    Article  Google Scholar 

  9. Britanova, O.V. et al. J. Immunol. 192, 2689–2698 (2014).

    CAS  Article  Google Scholar 

  10. Wang, C. et al. J. Immunol. 192, 603–611 (2014).

    CAS  Article  Google Scholar 

  11. Nguyen, P. et al. BMC Genomics 12, 106 (2011).

    CAS  Article  Google Scholar 

  12. Bolotin, D.A. et al. Eur. J. Immunol. 42, 3073–3083 (2012).

    CAS  Article  Google Scholar 

  13. Campbell, P.J. et al. Proc. Natl. Acad. Sci. USA 105, 13081–13086 (2008).

    CAS  Article  Google Scholar 

  14. Logan, A.C. et al. Proc. Natl. Acad. Sci. USA 108, 21194–21199 (2011).

    CAS  Article  Google Scholar 

  15. Kivioja, T. et al. Nat. Methods 9, 72–74 (2012).

    CAS  Article  Google Scholar 

  16. Kinde, I., Wu, J., Papadopoulos, N., Kinzler, K.W. & Vogelstein, B. Proc. Natl. Acad. Sci. USA 108, 9530–9535 (2011).

    Article  Google Scholar 

  17. Douek, D.C. et al. J. Immunol. 168, 3099–3104 (2002).

    CAS  Article  Google Scholar 

  18. Bolotin, D.A. et al. Nat. Methods 10, 813–814 (2013).

    CAS  Article  Google Scholar 

  19. Shapiro, E., Biezuner, T. & Linnarsson, S. Nat. Rev. Genet. 14, 618–630 (2013).

    CAS  Article  Google Scholar 

  20. Brodin, J. et al. PLoS ONE 8, e70388 (2013).

    CAS  Article  Google Scholar 

  21. Brochet, X., Lefranc, M.-P. & Giudicelli, V. Nucleic Acids Res. 36, W503–W508 (2008).

    CAS  Article  Google Scholar 

  22. Ye, J., Ma, N., Madden, T.L. & Ostell, J.M. Nucleic Acids Res. 41, W34–W40 (2013).

    Article  Google Scholar 

  23. Glanville, J. et al. Proc. Natl. Acad. Sci. USA 106, 20216–20221 (2009).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We are grateful to M. Eisenstein for the English editing. This work was supported by the Molecular and Cell Biology program RAS, Russian Foundation for Basic Research 12-04-33139 (to D.M.C.), 13-04-00998 (to O.V.B.) and 14-04-01247 (to E.M.M.), Russian President grant MD-3044.2014.4 (to D.M.C.) and European Regional Development Fund (CZ.1.05/1.1.00/02.0068).

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Authors and Affiliations

Authors

Contributions

M.S., O.V.B., D.A.B., D.S., S.P. and D.M.C. designed experiments. O.V.B., E.M.M., M.A.T., I.Z.M., T.R.T., D.B.S., E.V.P., K.P. and C.L. performed experiments. M.S., D.A.B. and D.M.C. designed the MIGEC algorithm and analyzed and interpreted results. M.S., S.L., T.N.S. and D.M.C. wrote the manuscript.

Corresponding author

Correspondence to Dmitriy M Chudakov.

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The authors declare no competing financial interests.

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Supplementary Figures 1–11 and Supplementary Tables 1–4 (PDF 4939 kb)

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Shugay, M., Britanova, O., Merzlyak, E. et al. Towards error-free profiling of immune repertoires. Nat Methods 11, 653–655 (2014). https://doi.org/10.1038/nmeth.2960

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