NAME
SYNOPSIS hmmfs [options] hmmfile seqfile DESCRIPTION hmmfs searches a sequence database seqfile looking for matches to the HMM in hmmfile. An optimal set of non-overlapping multiple hits to subsequences and to fragments of the model are allowed for each database sequence -- i.e., the program does a multiple-hit variant of Smith/Waterman searching.
hmmfs is designed to be particularly useful for detecting repeated motifs in long sequences. It has been used successfully for Alu detection in human cosmid sequences, and for recognizing multiple tandem domains in mosaic proteins.
The memory requirement is linear in the length of the longest database sequence, not quadratic, permitting very long genomic DNA sequences (> 1 Mb) to be searched.
The scores reported by hmmfs are in bits of information. Specifically, they are log-odds scores: the log of the ratio of the probability of the sequence given the model and the probability of the sequence given a simple random sequence model. This score is related to the statistical significance of the alignment. A score of zero is marginal; according to the model's statistics, it's 50% likely that the alignment is a real match to the model, and 50% likely that it's not. The higher the score, the better; a score of 100 means that it is 2par100-fold more likely that the sequence is a match to the model than not. In practice, a database contains many more unrelated sequences than related ones, so the actual score required for statistical significance is somewhat higher than zero -- as a rule of thumb for protein database searches, don't trust scores lower than the log2 of the number of seqs in the database). This is 16 bits for our current SWIR5 composite protein database of 57,000 sequences. See the User Guide for more details.
Note the differences between the different HMM searching programs. hmms looks for a global alignment of HMM to sequences (Needleman/Wunsch style); overhangs of unmatches sequence are not permitted, and the full model must be matched. hmmls looks for one or more local alignments of the full model to a subsequence of each database sequence; unmatches sequence overhangs are allowed. hmmsw looks for the best fragmentary match of a subsequence to part of the model (Smith/Waterman style). hmmfs looks for multiple non-overlapping matches of subsequences to parts of the model (modified multiple-hit Smith/Waterman). hmms is useful for scoring or detecting whole proteins with complete models; hmmls is useful for scoring or detecting intact domains in protein sequences or complete repeats in nucleic acid sequences; hmmsw is useful for general protein database searching, allowing for possible incomplete matches to a model; hmmfs is useful for general nucleic acid database searching or for scoring/detecting domains in multidomain proteins, allowing for multiple non-overlapping matches per sequence.
OPTIONS
SEE ALSO
Overview page: hmmer(l)
Individual man pages: hmma(l), hmmb(l), hmme(l), hmmls(l), hmms(l), hmmsw(l), hmmt(l), hmm-convert(l)
User guide and tutorial: Userguide.ps
BUGS No major bugs known.
Not very tolerant of errors on the command line.
NOTES This software and documentation is Copyright (C) 1992-1995, Sean R. Eddy. It is freely distributable under terms of the GNU General Public License. See COPYING, in the source code distribution, for more details, or contact me.
Sean Eddy Dept. of Genetics, Washington Univ. School of Medicine 660 S. Euclid Box 8232 St Louis, MO 63110 USA Phone: 1-314-362-7666 FAX : 1-314-362-2985 Email: eddy@genetics.wustl.edu