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Bioinformatics Advance Access published online on July 20, 2009
Bioinformatics, 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 1,* and Erik L.L. Sonnhammer 1

1Stockholm Bioinformatics Center, Stockholm University, SE-10691 Stockholm, Sweden

*To whom correspondence should be addressed. Mr. Kristoffer Forslund, E-mail: Kristoffer.Forslund{at}sbc.su.se


  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: See journal webpage.

Associate Editor: Prof. Dmitrij Frishman

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

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