Localized Genome Assembly from Reads to Scaffolds: Practical Traversal of the Paired String Graph

  • Rayan Chikhi
  • Dominique Lavenier
Part of the Lecture Notes in Computer Science book series (LNCS, volume 6833)

Abstract

Next-generation de novo short reads assemblers typically use the following strategy: (1) assemble unpaired reads using heuristics leading to contigs; (2) order contigs from paired reads information to produce scaffolds. We propose to unify these two steps by introducing localized assembly: direct construction of scaffolds from reads. To this end, the paired string graph structure is introduced, along with a formal framework for building scaffolds as paths of reads. This framework leads to the design of a novel greedy algorithm for memory-efficient, parallel assembly of paired reads. A prototype implementation of the algorithm has been developed and applied to the assembly of simulated and experimental short reads. Our experiments show that our methods yields longer scaffolds than recent assemblers, and is capable of assembling diploid genomes significantly better than other greedy methods.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ariyaratne, P.N., Sung, W.: PE-Assembler: de novo assembler using short paired-end reads. Bioinformatics (December 2010)Google Scholar
  2. 2.
    Batzoglou, S., Jaffe, D.B., Stanley, K., Butler, J., Gnerre, S., Mauceli, E., Berger, B., Mesirov, J.P., Lander, E.S.: ARACHNE: a whole-genome shotgun assembler. Genome Research 12(1), 177 (2002)CrossRefGoogle Scholar
  3. 3.
    Boisvert, S., Laviolette, F., Corbeil, J.: Ray: Simultaneous assembly of reads from a mix of High-Throughput sequencing technologies. Journal of Computational Biology, 3389–3402 (2010)Google Scholar
  4. 4.
    Bryant, D.W., Wong, W.K., Mockler, T.C.: QSRA – a quality-value guided de novo short read assembler. BMC Bioinformatics 10(1), 69 (2009)CrossRefGoogle Scholar
  5. 5.
    Butler, J., MacCallum, I., Kleber, M., Shlyakhter, I.A., Belmonte, M.K., Lander, E.S., Nusbaum, C., Jaffe, D.B.: ALLPATHS: de novo assembly of whole-genome shotgun microreads. Genome Research 18(5), 810–820 (2008), http://genome.cshlp.org/content/18/5/810.abstract CrossRefGoogle Scholar
  6. 6.
    Chikhi, R., Lavenier, D.: Paired-end read length lower bounds for genome re-sequencing. BMC Bioinformatics 10(suppl. 13), O2 (2009)CrossRefGoogle Scholar
  7. 7.
    Donmez, N., Brudno, M.: Hapsembler: An assembler for highly polymorphic genomes. In: Bafna, V., Sahinalp, S.C. (eds.) RECOMB 2011. LNCS, vol. 6577, pp. 38–52. Springer, Heidelberg (2011)CrossRefGoogle Scholar
  8. 8.
    Ferragina, P., Manzini, G.: Indexing compressed text. Journal of the ACM (JACM) 52(4), 552–581 (2005)CrossRefMATHGoogle Scholar
  9. 9.
    Gnerre, S., MacCallum, I., Przybylski, D., Ribeiro, F.J., Burton, J.N., Walker, B.J., Sharpe, T., Hall, G., Shea, T.P., Sykes, S., Berlin, A.M., Aird, D., Costello, M., Daza, R., Williams, L., Nicol, R., Gnirke, A., Nusbaum, C., Lander, E.S., Jaffe, D.B.: High-quality draft assemblies of mammalian genomes from massively parallel sequence data. Proceedings of the National Academy of Sciences 108(4), 1513–1518 (2011), http://www.pnas.org/content/108/4/1513.abstract CrossRefGoogle Scholar
  10. 10.
    Hossain, M., Azimi, N., Skiena, S.: Crystallizing short-read assemblies around seeds. BMC Bioinformatics 10(suppl. 1), S16 (2009), http://www.biomedcentral.com/1471-2105/10/S1/S16 CrossRefGoogle Scholar
  11. 11.
    Huson, D.H., Reinert, K., Myers, E.W.: The greedy path-merging algorithm for contig scaffolding. Journal of the ACM (JACM) 49(5), 603–615 (2002)CrossRefMATHGoogle Scholar
  12. 12.
    Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R.: The sequence alignment/map format and SAMtools. Bioinformatics 25(16), 2078 (2009)CrossRefGoogle Scholar
  13. 13.
    Li, R., Zhu, H., Ruan, J., Qian, W., Fang, X., Shi, Z., Li, Y., Li, S., Shan, G., Kristiansen, K., Li, S., Yang, H., Wang, J., Wang, J.: De novo assembly of human genomes with massively parallel short read sequencing. Genome Research 20(2), 265–272 (2010), http://genome.cshlp.org/content/20/2/265.abstract CrossRefGoogle Scholar
  14. 14.
    Medvedev, P., Pham, S., Chaisson, M., Tesler, G., Pevzner, P.: Paired de bruijn graphs: A novel approach for incorporating mate pair information into genome assemblers. In: Bafna, V., Sahinalp, S.C. (eds.) RECOMB 2011. LNCS, vol. 6577, pp. 238–251. Springer, Heidelberg (2011)CrossRefGoogle Scholar
  15. 15.
    Miller, J.R., Koren, S., Sutton, G.: Assembly algorithms for next-generation sequencing data. Genomics (2010)Google Scholar
  16. 16.
    Myers, E.W.: Toward simplifying and accurately formulating fragment assembly. Journal of Computational Biology 2(2), 275–290 (1995)CrossRefGoogle Scholar
  17. 17.
    Nagarajan, N., Pop, M.: Parametric complexity of sequence assembly: Theory and applications to next generation sequencing. Journal of Computational Biology 16(7), 897–908 (2009)CrossRefGoogle Scholar
  18. 18.
    Pop, M., Kosack, D.S., Salzberg, S.L.: Hierarchical scaffolding with bambus. Genome Research 14(1), 149–159 (2004), http://genome.cshlp.org/content/14/1/149.abstract CrossRefGoogle Scholar
  19. 19.
    Schmidt, B., Sinha, R., Beresford-Smith, B., Puglisi, S.J.: A fast hybrid short read fragment assembly algorithm. Bioinformatics 25(17), 2279 (2009)CrossRefGoogle Scholar
  20. 20.
    Simpson, J.T., Durbin, R.: Efficient construction of an assembly string graph using the FM-index. Bioinformatics 26(12), i367 (2010)CrossRefGoogle Scholar
  21. 21.
    Simpson, J., Wong, K., Jackman, S., Schein, J., Jones, S., Birol, İ.: ABySS: A parallel assembler for short read sequence data. Genome Research 19(6), 1117 (2009)CrossRefGoogle Scholar
  22. 22.
    Sutton, G., Miller, J.R., Delcher, A.L., Koren, S., Venter, E., Walenz, B.P., Brownley, A., Johnson, J., Li, K., Mobarry, C.: Aggressive assembly of pyrosequencing reads with mates. Bioinformatics 24(24), 2818–2824 (2008), http://bioinformatics.oxfordjournals.org/cgi/content/abstract/24/24/2818 CrossRefGoogle Scholar
  23. 23.
    Warren, R.L., Sutton, G.G., Jones, S.J.M., Holt, R.A.: Assembling millions of short DNA sequences using SSAKE. Bioinformatics 23(4), 500–501 (2007), http://bioinformatics.oxfordjournals.org/cgi/content/abstract/23/4/500 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), http://genome.cshlp.org/content/18/5/821.abstract CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Rayan Chikhi
    • 1
  • Dominique Lavenier
    • 1
  1. 1.Computer Science departmentENS Cachan/IRISARennesFrance

Personalised recommendations