For each multiple sequence alignment in <msafile> build a profile HMM and save it to a new file <hmmfile out>.
The alphabet type (amino, DNA, or RNA) is autodetected by default, by looking at the composition of the msafile. Autodetection is normally quite reliable, but occasionally alphabet type may be ambiguous and autodetection can fail (for instance, on tiny toy alignments of just a few residues). To avoid this, or to increase robustness in automated analysis pipelines, you may specify the alphabet type of msafile with these options.
Options Controlling Profile Construction
These options control how consensus columns are defined in an alignment.
--fast
Define consensus columns as those that have a fraction >= symfrac of residues as opposed to gaps. (See below for the --symfrac option.) This is the default.
--hand
Define consensus columns in next profile using reference annotation to the multiple alignment. This allows you to define any consensus columns you like.
--symfrac
Define the residue fraction threshold necessary to define a consensus column when using the --fast option. The default is 0.5. The symbol fraction in each column is calculated after taking relative sequence weighting into account, and ignoring gap characters corresponding to ends of sequence fragments (as opposed to internal insertions/deletions). Setting this to 0.0 means that every alignment column will be assigned as consensus, which may be useful in some cases. Setting it to 1.0 means that only columns that include 0 gaps (internal insertions/deletions) will be assigned as consensus.
--fragthresh
We only want to count terminal gaps as deletions if the aligned sequence is known to be full-length, not if it is a fragment (for instance, because only part of it was sequenced). HMMER uses a simple rule to infer fragments: if the sequence length L is less than or equal to a fraction <x> times the alignment length in columns, then the sequence is handled as a fragment. The default is 0.5. Setting --fragthresh0 will define no (nonempty) sequence as a fragment; you might want to do this if you know you’ve got a carefully curated alignment of full-length sequences. Setting --fragthresh1 will define all sequences as fragments; you might want to do this if you know your alignment is entirely composed of fragments, such as translated short reads in metagenomic shotgun data.
HMMER uses an ad hoc sequence weighting algorithm to downweight closely related sequences and up-weight distantly related ones. This has the effect of making models less biased by uneven phylogenetic representation. For example, two identical sequences would typically each receive half the weight that one sequence would. These options control which algorithm gets used.
--wpb
Use the Henikoff position-based sequence weighting scheme [Henikoff and Henikoff, J. Mol. Biol. 243:574, 1994]. This is the default.
--wgsc
Use the Gerstein/Sonnhammer/Chothia weighting algorithm [Gerstein et al, J. Mol. Biol. 235:1067, 1994].
--wblosum
Use the same clustering scheme that was used to weight data in calculating BLOSUM subsitution matrices [Henikoff and Henikoff, Proc. Natl. Acad. Sci 89:10915, 1992]. Sequences are single-linkage clustered at an identity threshold (default 0.62; see --wid) and within each cluster of c sequences, each sequence gets rela- tive weight 1/c.
--wnone
No relative weights. All sequences are assigned uniform weight.
--wid
Sets the identity threshold used by single-linkage clustering when using --wblosum. Invalid with any other weighting scheme. Default is 0.62.
After relative weights are determined, they are normalized to sum to a total effective sequence number, eff nseq. This number may be the actual number of sequences in the alignment, but it is almost always smaller than that. The default entropy weighting method (--eent) reduces the effective sequence num- ber to reduce the information content (relative entropy, or average expected score on true homologs) per consensus position. The target relative entropy is controlled by a two-parameter function, where the two parameters are settable with --ere and --esigma.
--eent
Adjust effective sequence number to achieve a specific relative entropy per position (see --ere). This is the default.
--eclust
Set effective sequence number to the number of single-linkage clusters at a specific identity threshold (see --eid). This option is not recommended; it’s for experiments evaluating how much better --eent is.
--enone
Turn off effective sequence number determination and just use the actual number of sequences. One reason you might want to do this is to try to maximize the relative entropy/position of your model, which may be useful for short models.
--eset
Explicitly set the effective sequence number for all models to <x>.
--ere
Set the minimum relative entropy/position target to <x>. Requires --eent. Default depends on the sequence alphabet. For protein sequences, it is 0.59 bits/position; for nucleotide sequences, it is 0.45 bits/position.
--esigma
Sets the minimum relative entropy contributed by an entire model alignment, over its whole length. This has the effect of making short models have higher relative entropy per position than --ere alone would give. The default is 45.0 bits.
--eid
Sets the fractional pairwise identity cutoff used by single linkage clustering with the --eclust option. The default is 0.62.
By default, weighted counts are converted to mean posterior probability parameter estimates using mixture Dirichlet priors. Default mixture Dirichlet prior parameters for protein models and for nucleic acid (RNA and DNA) models are built in. The following options allow you to override the default priors.
No priors (--pnone)
Don’t use any priors. Probability parameters will simply be the observed frequencies, after relative sequence weighting.
Laplace +1 prior
Use a Laplace +1 prior in place of the default mixture Dirichlet prior.
By default, the first iteration uses a search model constructed from a single query sequence. This model is constructed using a standard 20x20 substitution matrix for residue probabilities, and two additional pa- rameters for position-independent gap open and gap extend probabilities. These options allow the default single-sequence scoring parameters to be changed.
Gap Open (--popen)
Set the gap open probability for a single sequence query model to <x>
Gap Extend (--pextend)
Set the gap extend probability for a single sequence query model to <x>.
--mx/--mxfile
These options are not currently supported
H3 uses three short random sequence simulations to estimating the location parameters for the expected score distributions for MSV scores, Viterbi scores, and Forward scores. These options allow these simulations to be modified.
--EmL
Sets the sequence length in simulation that estimates the location parameter mu for MSV E-values. Default is 200.
--EmN
Sets the number of sequences in simulation that estimates the location parameter mu for MSV E-values. Default is 200.
--EvL
Sets the sequence length in simulation that estimates the location parameter mu for Viterbi E-values. Default is 200.
--EvN
Sets the number of sequences in simulation that estimates the location parameter mu for Viterbi E-values. Default is 200.
--EfL
Sets the sequence length in simulation that estimates the location parameter tau for Forward E-values. Default is 100.
--EfN
Sets the number of sequences in simulation that estimates the location parameter tau for Forward E-values. Default is 200.
--Eft
Sets the tail mass fraction to fit in the simulation that estimates the location param- eter tau for Forward evalues. Default is 0.04.
Seed the random number generator with <n>, an integer >= 0. If <n> is nonzero, any stochastic simulations will be reproducible; the same command will give the same results. If <n> is 0, the random number generator is seeded arbitrarily, and stochastic simulations will vary from run to run of the same command.
Window length tail mass (--w_beta)
The upper bound, W, on the length at which nhmmer expects to find an instance of the model is set such that the fraction of all sequences generated by the model with length >= W is less than <x>. The default is 1e-7.
Model instance length upper bound (--w length)
Override the model instance length upper bound, W, which is otherwise controlled by --w beta. It should be larger than the model length. The value of W is used deep in the acceleration pipeline, and modest changes are not expected to impact results (though larger values of W do lead to longer run time).
This Galaxy tool relies on HMMER3 from http://hmmer.janelia.org/ Internally the software is cited as:
# hmmscan :: search sequence(s) against a profile database # HMMER 3.1 (February 2013); http://hmmer.org/ # Copyright (C) 2011 Howard Hughes Medical Institute. # Freely distributed under the GNU General Public License (GPLv3). # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
The wrappers were written by Eric Rasche and is licensed under Apache2. The documentation is copied from the HMMER3 documentation.