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Bioinformatics Advance Access originally published online on July 20, 2009
Bioinformatics 2009 25(19):2500-2505; doi:10.1093/bioinformatics/btp446
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Benchmarking homology detection procedures with low complexity filters

Kristoffer Forslund * and Erik LL Sonnhammer

Stockholm Bioinformatics Center, Stockholm University, SE-10691 Stockholm, Sweden

*To whom correspondence should be addressed.


  Abstract

Background: Low-complexity sequence regions present a common problem in finding true homologs to a protein query sequence. Several solutions to this have been suggested, but a detailed comparison between these on challenging data has so far been lacking. A common benchmark for homology detection procedures is to use SCOP/ASTRAL domain sequences belonging to the same or different superfamilies, but these contain almost no low complexity sequences.

Results: We here introduce an alternative benchmarking strategy based around Pfam domains and clans on whole-proteome data sets. This gives a realistic level of low complexity sequences. We used it to evaluate all six built-in BLAST low complexity filter settings as well as a range of settings in the MSPcrunch post-processing filter. The effect on alignment length was also assessed.

Conclusion: Score matrix adjustment methods provide a low false positive rate at a relatively small loss in sensitivity relative to no filtering, across the range of test conditions we apply. MSPcrunch achieved even less loss in sensitivity, but at a higher false positive rate. A drawback of the score matrix adjustment methods is however that the alignments often become truncated.

Availability: Perl scripts for MSPcrunch BLAST filtering and for generating the benchmark dataset are available at http://sonnhammer.sbc.su.se/download/software/MSPcrunch+Blixem/benchmark.tar.gz

Contact: kristoffer.forslund{at}sbc.su.se

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Dmitrij Frishman

Received on March 16, 2009; revised on July 14, 2009; accepted on July 15, 2009

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Nucleic Acids Res., November 5, 2009; (2009) gkp931v1.
[Abstract] [Full Text] [PDF]


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