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Evaluating the Statistical Significance of Multiple Distinct Local Alignments

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Theoretical and Computational Methods in Genome Research

Abstract

A comparison of two sequences may uncover multiple regions of local similarity. While the significance of each local alignment may be evaluated independently, sometimes a combined assessment is appropriate. This paper discusses a variety of statistical and algorithmic issues that such an assessment presents.

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References

  1. Smith, T.F. & Waterman, M.S. (1981). Identification of common molecular subsequences. J. Mol. Biol. 147:195–197.

    Article  PubMed  CAS  Google Scholar 

  2. Pearson, W.R. & Lipman, D.J. (1988). Improved tools for biological sequence comparison. Proc. Natl. Acad. Sci. U.S.A. 85:2444–2448.

    Article  PubMed  CAS  Google Scholar 

  3. Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. (1990). Basic local alignment search tool. J. Mol. Biol. 215:403–410.

    PubMed  CAS  Google Scholar 

  4. Smith, T.F., Waterman, M.S. & Burks, C. (1985). The statistical distribution of nucleic acid similarities. Nucl. Acids Res. 13:645–656.

    Article  PubMed  CAS  Google Scholar 

  5. Altschul, S.F. & Erickson, B.W. (1986). A nonlinear measure of subalignment similarity and its significance levels. Bull. Math. Biol. 48:617–632.

    PubMed  CAS  Google Scholar 

  6. Arratia, R., Gordon, L. & Waterman, M.S. (1986). An extreme value theory for sequence matching. Ann. Stat. 14:971–993.

    Article  Google Scholar 

  7. Collins, J.F., Coulson, A.F.W. & Lyall, A. (1988). The significance of protein sequence similarities. CABIOS 4:67–71.

    PubMed  CAS  Google Scholar 

  8. Arratia, R. & Waterman, M.S. (1989). The Erdos-Renyi strong law for pattern matching with a given proportion of mismatches. Ann. Prob. 17:1152–1169.

    Article  Google Scholar 

  9. Karlin, S. & Altschul, S.F. (1990). Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. Proc. Natl. Acad. Sci. U.S.A. 87:2264–2268

    Article  PubMed  CAS  Google Scholar 

  10. Dembo, A. & Karlin, S. (1991). Strong limit theorems of empirical functionals for large exceedances of partial sums of i.i.d. variables. Ann. Prob. 19:1737–1755.

    Article  Google Scholar 

  11. Dembo, A. & Karlin, S. (1991). Strong limit theorems of empirical distributions for large segmental exceedances of partial sums of Markov variables. Ann. Prob. 19:1756–1767.

    Article  Google Scholar 

  12. Mott, R. (1992). Maximum-likelihood estimation of the statistical distribution of Smith-Waterman local sequence similarity scores. Bull. Math. Biol. 54:59–75.

    Google Scholar 

  13. Altschul, S.F. (1993). A protein alignment scoring system sensitive at all evolutionary distances. J. Mol. Evol. 36:290–300.

    Article  PubMed  CAS  Google Scholar 

  14. Arratia, R. & Waterman, M.S. (1994). A phase transition for the score in matching random sequences allowing deletions. Ann. Appl. Prob. 4:200–225.

    Article  Google Scholar 

  15. Dembo, A., Karlin, S. & Zeitouni, O. (1994). Limit distribution of maximal non-aligned two-sequence segmental score. Ann. Prob. 22:2022–2039.

    Article  Google Scholar 

  16. Waterman, M.S. & Vingron, M. (1994). Sequence comparison significance and Poisson approximation. Stat. Sci. 9:367–381.

    Article  Google Scholar 

  17. Altschul, S.F. & Gish, W. (1996). Local alignment statistics. Meth. Enzymol. 266:460–480.

    Article  PubMed  CAS  Google Scholar 

  18. Sellers, P.H. (1984). Pattern recognition in genetic sequences by mismatch density. Bull. Math. Biol. 46:501–514

    CAS  Google Scholar 

  19. Altschul, S.F. & Erickson, B.W. (1986). Locally optimal subalignments using nonlinear similarity functions. Bull. Math. Biol. 48:633–660.

    PubMed  CAS  Google Scholar 

  20. Waterman, M.S. & Eggert, M. (1987). A new algorithm for best subsequence alignments with applications to tRNA-rRNA comparisons. J. Mol. Biol. 197:723–728.

    Article  PubMed  CAS  Google Scholar 

  21. Huang, X., Hardison, R.C. & Miller, W. (1990). A space-efficient algorithm for local similarities. CABIOS 6:373–381.

    PubMed  CAS  Google Scholar 

  22. Karlin, S. & Altschul, S.F. (1993). Applications and statistics for multiple high-scoring segments in molecular sequences. Proc. Natl. Acad. Sci. U.S.A. 90:5873–5877.

    Article  PubMed  CAS  Google Scholar 

  23. Gumbel, E.J. (1958). Statistics of extremes. Columbia University Press, New York.

    Google Scholar 

  24. Woodsmall, R.M. & Benson, D.A. (1993). Information resources at the National Center for Biotechnology Information. Bull. Med. Libr. Assoc. 81:282–284.

    PubMed  CAS  Google Scholar 

  25. Altschul, S.F., Boguski, M.S., Gish, W. & Wootton, J.C. (1994). Issues in searching molecular sequence databases. Nature Genet. 6:119–129.

    Article  PubMed  CAS  Google Scholar 

  26. Henikoff, S. & Henikoff, J.G. (1991). Automated assembly of protein blocks for database searching. Nucleic Acids Res. 19:6565–6572.

    Article  PubMed  CAS  Google Scholar 

  27. Lawrence, C.E., Altschul, S.F., Boguski, M.S., Liu, J.S., Neuwald, A.F. & Wootton, J.C. (1993). Detecting subtle sequence signals: A Gibbs sampling strategy for multiple alignment. Science 262:208–214.

    Article  PubMed  CAS  Google Scholar 

  28. Altschul, S.F. (1991). Amino acid substitution matrices from an information theoretic perspective. J. Mol. Biol. 219:555–565.

    Article  PubMed  CAS  Google Scholar 

  29. Gotoh, O. (1982). An improved algorithm for matching biological sequences. J. Mol. Biol. 162:705–708.

    Article  PubMed  CAS  Google Scholar 

  30. Fitch, W.M. & Smith, T.F. (1983). Optimal sequence alignments. Proc. Natl. Acad. Sci. USA 80:1382–1386.

    Article  PubMed  CAS  Google Scholar 

  31. Altschul, S.F. & Erickson, B.W. (1986). Optimal sequence alignment using affine gap costs. Bull. Math. Biol. 48:603–616.

    PubMed  CAS  Google Scholar 

  32. Myers, E.W. & Miller, W. (1988). Optimal alignments in linear space. CABIOS 4:11–17.

    PubMed  CAS  Google Scholar 

  33. Henikoff, S. & Henikoff, J.G. (1992). Amino acid substitution matrices from protein blocks. Proc. Natl. Acad. Sci. USA 89:10915–10919.

    Article  PubMed  CAS  Google Scholar 

  34. Bairoch, A. & Boeckmann, B. (1994). The SWISS-PROT protein sequence data bank: current status. Nucleic Acids Res. 22:3578–3580.

    Article  PubMed  CAS  Google Scholar 

  35. Xu, G.F., O’Connell, P., Viskochil, D., Cawthon, R., Robertson, M., Culver, M., Dunn, D., Stevens, J., Gesteland, R., White, R. & Weiss, R. (1990). The neurofibromatosis type I gene encodes a protein related to GAP. Cell 62:599–608.

    Article  PubMed  CAS  Google Scholar 

  36. Cvrckova, F. & Nasmyth, K. (1993). Yeast G1 cyclins CLNI and CLN2 and a GAP-like protein have a role in bud formation. EMBO J. 12:5277–5286.

    PubMed  CAS  Google Scholar 

  37. Wootton, J.C. & Federhen, S. (1993). Statistics of local complexity in amino acid sequences and sequence databases. Comput. Chem. 17:149–163.

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. National Center for Biotechnology Information National Library of Medicine, National Institutes of Health, Bethesda, Maryland, 20894, USA

    Stephen F. Altschul

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  1. Stephen F. Altschul
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Editor information

Editors and Affiliations

  1. German Cancer Research Center, Heidelberg, Germany

    Sándor Suhai

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© 1997 Springer Science+Business Media New York

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Altschul, S.F. (1997). Evaluating the Statistical Significance of Multiple Distinct Local Alignments. In: Suhai, S. (eds) Theoretical and Computational Methods in Genome Research. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5903-0_1

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  • DOI: https://doi.org/10.1007/978-1-4615-5903-0_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7708-5

  • Online ISBN: 978-1-4615-5903-0

  • eBook Packages: Springer Book Archive

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