Remote Homology Detection of HMMERHEAD and HMMER 2.5.1 Forward and Viterbi. Each of the 2,521 benchmarking models was scored against the test database using either HMMER 2.5.1 or HMMERHEAD with Forward or Viterbi scoring. The results of the searches were combined and scored. This procedure was then repeated for each of the 1000 bootstrapping replicate test sets. The average number of true positives was plotted versus errors per query. Minimum and maximum numbers of true positives from the replicates are shown as error bars. HMMERHEAD Forward (Red) performance is shown relative to default HMMER 2.5.1 Forward (Blue), WU-BLAST (Black dashed), and WU-BLAST Family Pairwise Search (Black). Default HMMERHEAD Forward detects an average of 269 fewer true positives than default HMMER 2.5.1 Forward and detects significantly more true positives than either pairwise sequence comparison method. HMMERHEAD Viterbi (Red dashed) performance is shown relative to default HMMER 2.5.1 Viterbi (Blue dashed). Default HMMERHEAD Viterbi detects an average of 173 fewer true positives than default HMMER 2.5.1 Viterbi and again outperforms either pairwise comparison method. The total number of true homologous pairs between the 2,521 models and the test database is 39,733, and thus 8,000 true positives correspond to identifying 20% of the homologs.