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BLOSUM62 miscalculations improve search performance

Nature Biotechnology volume 26, pages 274–275 (2008)Cite this article

To the editor:

The BLOSUM1 family of substitution matrices, and particularly BLOSUM62, is the de facto standard in protein database searches and sequence alignments. In the course of analyzing the evolution of the Blocks database2, we noticed errors in the software source code used to create the initial BLOSUM family of matrices (available online at ftp://ftp.ncbi.nih.gov/repository/blocks/unix/blosum/blosum.tar.Z). The result of these errors is that the BLOSUM matrices—BLOSUM62, BLOSUM50, etc.—are quite different from the matrices that should have been calculated using the algorithm described by Henikoff and Henikoff1. Obviously, minor errors in research, and particularly in software source code, are quite common. This case is noteworthy for three reasons: first, the BLOSUM matrices are ubiquitous in computational biology; second, these errors have gone unnoticed for 15 years; and third, the 'incorrect' matrices perform better than the 'intended' matrices.

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Figure 1: Performance difference between BLOSUM62 and RBLOSUM64 as assessed by pairwise sequence comparison evaluation (PSCE) tools4.

References

  1. Henikoff, S. & Henikoff, J.G. Proc. Natl. Acad. Sci. USA 89, 10915–10919 (1992).

    Article  CAS  Google Scholar 

  2. Henikoff, J.G., Greene, E.A., Pietrokovski, S. & Henikoff, S. Nucleic Acids Res. 28, 228–230 (2000).

    Article  CAS  Google Scholar 

  3. Altschul, S.F. J. Mol. Biol. 219, 555–565 (1991).

    Article  CAS  Google Scholar 

  4. Price, G.A., Crooks, G.E., Green, R.E. & Brenner, S.E. Bioinformatics 21, 3824–3831 (2005).

    Article  CAS  Google Scholar 

  5. Smith, T.F. & Waterman, M.S. J. Mol. Biol. 147, 195–197 (1981).

    Article  CAS  Google Scholar 

  6. Pearson, W.R. Methods Enzymol. 183, 63–98 (1990).

    Article  CAS  Google Scholar 

  7. Pearson, W.R. Genomics 11, 635–650 (1991).

    Article  CAS  Google Scholar 

  8. Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. J. Mol. Biol. 215, 403–410 (1990).

    Article  CAS  Google Scholar 

  9. Brenner, S.E., Koehl, P. & Levitt, M. Nucleic Acids Res. 28, 254–256 (2000).

    Article  CAS  Google Scholar 

  10. Murzin, A.G., Brenner, S.E., Hubbard, T. & Chothia, C. J. Mol. Biol. 247, 536–540 (1995).

    CAS  PubMed  Google Scholar 

  11. Henikoff, S., Henikoff, J.G., Alford, W.J. & Pietrokovski, S. Gene 162, GC17–GC26 (1995).

    Google Scholar 

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Author notes

  1. Mark P Styczynski

    Present address: Current address: Broad Institute, Room 6175X, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.,

  2. Mark P Styczynski and Kyle L Jensen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469c, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Mark P Styczynski & Gregory Stephanopoulos

  2. Department of Plant Sciences, Public Intellectual Property Resource for Agriculture, University of California, One Shields Avenue, Plant Reproductive Biology Building–Mail Stop 5, Davis, 95616, California, USA

    Kyle L Jensen

  3. Harvard-MIT Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Kyle L Jensen

  4. IBM Research Division, Thomas J. Watson Research Center, 1101 Kitchawan Road, PO Box 218, Yorktown Heights, 10598, New York, USA

    Isidore Rigoutsos

Authors
  1. Mark P Styczynski
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  2. Kyle L Jensen
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  3. Isidore Rigoutsos
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  4. Gregory Stephanopoulos
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Styczynski, M., Jensen, K., Rigoutsos, I. et al. BLOSUM62 miscalculations improve search performance. Nat Biotechnol 26, 274–275 (2008). https://doi.org/10.1038/nbt0308-274

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