Advertisement

Immunoglobulin Classification Using the Colored Antibody Graph

  • Stefano R. BonissoneEmail author
  • Pavel A. Pevzner
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 9029)

Abstract

The somatic recombination of V, D, and J gene-segments in B-cells, introduces a great deal of diversity, and divergence from reference segments. Many recent studies of antibodies focus on the population of antibody transcripts that show which V, D, and J gene-segments have been favored for a particular antigen, a repertoire. To properly describe the antibody repertoire, each antibody must be labeled by its constituting V, D, and J gene-segment, a task made difficult by somatic recombination and hypermutation events. While previous approaches to repertoire analysis were based on sequential alignments, we describe a new de Bruijn graph based algorithm to perform VDJ labeling, and benchmark its performance.

Keywords

Simulated Dataset Jaccard Index Somatic Hypermutation Nucleic Acid Research Antibody Repertoire 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Angly, F.E., Willner, D., Rohwer, F., Hugenholtz, P., Tyson, G.W.: Grinder: a versatile amplicon and shotgun sequence simulator. Nucleic Acids Research 40(12), e94–e94 (2012)CrossRefGoogle Scholar
  2. 2.
    Arnaout, R., Lee, W., Cahill, P., Honan, T., Sparrow, T., Weiand, M., Nusbaum, C., Rajewsky, K., Koralov, S.: High-resolution description of antibody heavy-chain repertoires in humans. PloS One 6(8), e22365 (2011)CrossRefGoogle Scholar
  3. 3.
    Basu, M., Hegde, M.V., Modak, M.J.: Synthesis of compositionally unique dna by terminal deoxynucleotidyl transferase. Biochemical and Biophysical Research Communications 111(3), 1105–1112 (1983)CrossRefGoogle Scholar
  4. 4.
    Brochet, X., Lefranc, M., Giudicelli, V.: IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized VJ and VDJ sequence analysis. Nucleic Acids Research 36(suppl 2), W503–W508 (2008)CrossRefGoogle Scholar
  5. 5.
    Chen, W., Prabakaran, P., Zhu, Z., Feng, Y., Streaker, E., Dimitrov, D.: Identification of cross-reactive IgG antibodies from an acute HIV-1-infected patient using phage display and high-throughput sequencing technologies. Experimental and Molecular Pathology (2012)Google Scholar
  6. 6.
    Clark, L.A., Ganesan, S., Papp, S., van Vlijmen, H.W.: Trends in antibody sequence changes during the somatic hypermutation process. The Journal of Immunology 177(1), 333–340 (2006)CrossRefGoogle Scholar
  7. 7.
    Compeau, P.E., Pevzner, P.A., Tesler, G.: How to apply de Bruijn graphs to genome assembly. Nature Biotechnology 29(11), 987–991 (2011)CrossRefGoogle Scholar
  8. 8.
    Desiderio, S.V., Yancopoulos, G.D., Paskind, M., Thomas, E., Boss, M.A., Landau, N., Alt, F.W., Baltimore, D.: Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature 311, 752–755 (1984)CrossRefGoogle Scholar
  9. 9.
    Dörner, T., Foster, S.J., Farner, N.L., Lipsky, P.E.: Somatic hypermutation of human immunoglobulin heavy chain genes: targeting of RGYW motifs on both DNA strands. European Journal of Immunology 28(10), 3384–3396 (1998)CrossRefGoogle Scholar
  10. 10.
    Gaëta, B.A., Malming, H.R., Jackson, K.J., Bain, M.E., Wilson, P., Collins, A.M.: iHMMune-align: hidden Markov model-based alignment and identification of germline genes in rearranged immunoglobulin gene sequences. Bioinformatics 23(13), 1580–1587 (2007)CrossRefGoogle Scholar
  11. 11.
    Iqbal, Z., Caccamo, M., Turner, I., Flicek, P., McVean, G.: De novo assembly and genotyping of variants using colored de Bruijn graphs. Nature Genetics 44(2), 226–232 (2012)CrossRefGoogle Scholar
  12. 12.
    Jackson, K.J., Boyd, S., Gaëta, B.A., Collins, A.M.: Benchmarking the performance of human antibody gene alignment utilities using a 454 sequence dataset. Bioinformatics 26(24), 3129–3130 (2010)CrossRefGoogle Scholar
  13. 13.
    Jackson, K.J., Gaeta, B., Sewell, W., Collins, A.M.: Exonuclease activity and P nucleotide addition in the generation of the expressed immunoglobulin repertoire. BMC Immunology 5(1), 19 (2004)CrossRefGoogle Scholar
  14. 14.
    Jiang, N., He, J., Weinstein, J.A., Penland, L., Sasaki, S., He, X.S., Dekker, C.L., Zheng, N.Y., Huang, M., Sullivan, M., Wilson, P.C., Greenberg, H.B., Davis, M.M., Fisher, D.S., Quake, S.R.: Lineage structure of the human antibody repertoire in response to influenza vaccination. Science Translational Medicine 5(171), 171ra19 (2013)CrossRefGoogle Scholar
  15. 15.
    Ohm-Laursen, L., Nielsen, M., Larsen, S.R., Barington, T.: No evidence for the use of DIR, D-D fusions, chromosome 15 open reading frames or VHreplacement in the peripheral repertoire was found on application of an improved algorithm, JointML, to 6329 human immunoglobulin H rearrangements. Immunology 119(2), 265–277 (2006)CrossRefGoogle Scholar
  16. 16.
    Pevzner, P.A., Tang, H., Tesler, G.: De novo repeat classification and fragment assembly. Genome Research 14(9), 1786–1796 (2004)CrossRefGoogle Scholar
  17. 17.
    Robinson, J., Halliwell, J.A., McWilliam, H., Lopez, R., Parham, P., Marsh, S.G.: The IMGT/HLA database. Nucleic Acids Research 41(D1), D1222–D1227 (2013)CrossRefGoogle Scholar
  18. 18.
    Rogozin, I.B., Kolchanov, N.A.: Somatic hypermutagenesis in immunoglobulin genes: II. influence of neighbouring base sequences on mutagenesis. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression 1171(1), 11–18 (1992)CrossRefGoogle Scholar
  19. 19.
    Souto-Carneiro, M.M., Longo, N.S., Russ, D.E., Sun, H.W., Lipsky, P.E.: Characterization of the human Ig heavy chain antigen binding complementarity determining region 3 using a newly developed software algorithm, JOINSOLVER. The Journal of Immunology 172(11), 6790–6802 (2004)CrossRefGoogle Scholar
  20. 20.
    Volpe, J.M., Cowell, L.G., Kepler, T.B.: SoDA: implementation of a 3D alignment algorithm for inference of antigen receptor recombinations. Bioinformatics 22(4), 438–444 (2006)CrossRefGoogle Scholar
  21. 21.
    Wang, X., Wu, D., Zheng, S., Sun, J., Tao, L., Li, Y., Cao, Z.: Ab-origin: an enhanced tool to identify the sourcing gene segments in germline for rearranged antibodies. BMC Bioinformatics 9(Suppl 12), S20 (2008)CrossRefGoogle Scholar
  22. 22.
    Weinstein, J., Jiang, N., White, R., Fisher, D., Quake, S.: High-throughput sequencing of the zebrafish antibody repertoire. Science 324(5928), 807–810 (2009)CrossRefGoogle Scholar
  23. 23.
    Ye, J., Ma, N., Madden, T.L., Ostell, J.M.: IgBLAST: an immunoglobulin variable domain sequence analysis tool. Nucleic Acids Research 41(W1), W34–W40 (2013)CrossRefGoogle Scholar
  24. 24.
    Zerbino, D.R., Birney, E.: Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Research 18(5), 821–829 (2008)CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Bioinformatics Program and Department of Computer Science and EngineeringUniversity of California at San DiegoSan Diego, La JollaUSA

Personalised recommendations