Novel Computational Methods for Large Scale Genome Comparison

  • Todd J. Treangen
  • Xavier Messeguer
Part of the Advances in Soft Computing book series (AINSC, volume 49)

Summary

The current wealth of available genomic data provides an unprecedented opportunity to compare and contrast evolutionary histories of closely and distantly related organisms. The focus of this dissertation is on developing novel algorithms and software for efficient global and local comparison of multiple genomes and the application of these methods for a biologically relevant case study. The thesis research is organized into three successive phases, specifically: (1) multiple genome alignment of closely related species, (2) local multiple alignment of interspersed repeats, and finally, (3) a comparative genomics case study of Neisseria. In Phase 1, we first develop an efficient algorithm and data structure for maximal unique match search in multiple genome sequences. We implement these contributions in an interactive multiple genome comparison and alignment tool, M-GCAT, that can efficiently construct multiple genome comparison frameworks in closely related species. In Phase 2, we present a novel computational method for local multiple alignment of interspersed repeats. Our method for local alignment of interspersed repeats features a novel method for gapped extensions of chained seed matches, joining global multiple alignment with a homology test based on a hidden Markov model (HMM). In Phase 3, using the results from the previous two phases we perform a case study of neisserial genomes by tracking the propagation of repeat sequence elements in attempt to understand why the important pathogens of the neisserial group have sexual exchange of DNA by natural transformation. In conclusion, our global contributions in this dissertation have focused on comparing and contrasting evolutionary histories of related organisms via multiple alignment of genomes.

Keywords

Comparative genomics genome alignment interspersed repeats suffix tree Hidden Markov Model DNA uptake sequences homologous recombination 

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References

  1. 1.
    Liolos, K., Tavernarakis, N., Hugenholtz, P., Kyrpides, N.: The Genomes On Line Database (GOLD) v.2: a monitor of genome projects worldwide. Nucleic Acids Research 34, 332–334 (2006)CrossRefGoogle Scholar
  2. 2.
    Edgar, R.: MUSCLE: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32 (2004)Google Scholar
  3. 3.
    Thompson, J.D., Higgins, D.G., Gibson, T.: Clustal W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673–4680 (1994)CrossRefGoogle Scholar
  4. 4.
    Notredame, C., Higgins, D.G., Heringa, J.: T-Coffee: A novel method for fast and accurate multiple sequence alignment. Journal of Molecular Biology 302, 205–217 (2000)CrossRefGoogle Scholar
  5. 5.
    Wang, L., Jiang, T.: On the complexity of multiple sequence alignment. J. Comput. Biol. 1, 337–348 (1994)CrossRefGoogle Scholar
  6. 6.
    Treangen, T.J., Roset, R., Messeguer, X.: Optimized search for common unique substrings, on both forward and reverse strands, in multiple DNA sequences. In: Poster proceedings of the 1st internation conference on Bioinformatics Research and Development BIRD (2007)Google Scholar
  7. 7.
    Treangen, T.J., Messeguer, X.: M-GCAT: Interactively and efficiently constructing large-scale multiple genome comparison frameworks in closely related species. BMC Bioinformatics 7, 433 (2006)CrossRefGoogle Scholar
  8. 8.
    Darling, A.E., Treangen, T.J., Zhang, L., Kuiken, C., Messeguer, X., Perna, N.T.: Procrastination leads to efficient filtration for local multiple alignment. In: Bücher, P., Moret, B.M.E. (eds.) WABI 2006. LNCS (LNBI), vol. 4175. Springer, Heidelberg (2006)CrossRefGoogle Scholar
  9. 9.
    Treangen, T.J., Darling, A.E., Ragan, M.A., Messeguer, X.: Gapped Extension for Local Multiple Alignment of Interspersed DNA Repeats. In: LNBI proceedings of the International Symposium on Bioinformatics Research and Applications ISBRA (2008)Google Scholar
  10. 10.
    Treangen, T.J., Ambur, O.H., Tonjum, T., Rocha, E.P.C.: The impact of the neisserial DNA uptake sequences on genome evolution and stability. Genome Biology 9(3), R60 (2008)CrossRefGoogle Scholar
  11. 11.
    Goodman, S.D., Scocca, J.J.: Factors influencing the specific interaction of Neisseria gonorrhoeae with transforming DNA. J. Bacteriol. 173, 5921–5923 (1991)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Todd J. Treangen
    • 1
    • 2
  • Xavier Messeguer
    • 3
  1. 1.Institut Pasteur, Microbial Evolutionary Genomics, CNRS, URA2171 
  2. 2.UPMC Univ Paris 06, Atelier de BioInformatiqueParisFrance
  3. 3.Dept. of SoftwareUniversitat Politècnica de CatalunyaBarcelonaSpain

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