Background: Profile hidden Markov model (HMM) techniques are among the most powerful methods for protein homology detection. Yet, the critical features for successful modelling are not fully known. In the present work we approached this by using two of the most popular HMM packages: SAM and HMMER. The programs' abilities to build models and score sequences were compared on a SCOP/Pfam based test set. The comparison was done separately for local and global HMM scoring. Results: Using default settings, SAM was overall more sensitive. SAM's model estimation was superior, while HMMER's model scoring was more accurate. Critical features for model building were then analysed by comparing the two packages' algorithmic choices and parameters. The weighting between prior probabilities and multiple alignment counts held the primary explanation why SAM's model building was superior. Our analysis suggests that HMMER gives too much weight to the sequence counts. SAM's...
Markus Wistrand, Erik L. L. Sonnhammer