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       hmmbuild - construct profile HMM(s) from multiple sequence alignment(s)


       hmmbuild [options] <hmmfile_out> <msafile>


       For each multiple sequence alignment in <msafile> build a profile HMM and save it to a new
       file <hmmfile_out>.

       <msafile> may be '-' (dash), which means reading this input from stdin rather than a file.
       To  use  '-',  you  must also specify the alignment file format with --informat <s>, as in
       --informat stockholm (because of a current limitation  in  our  implementation,  MSA  file
       formats cannot be autodetected in a nonrewindable input stream.)

       <hmmfile_out>  may  not  be  '-'  (stdout),  because  sending the HMM file to stdout would
       conflict with the other text output of the program.


       -h     Help; print a brief reminder of command line usage and all available options.

       -n <s> Name the new profile <s>.  The default is to use the name of the alignment (if  one
              is  present  in the msafile, or, failing that, the name of the hmmfile.  If msafile
              contains more than one alignment, -n doesn't work, and every alignment must have  a
              name annotated in the msafile (as in Stockholm #=GF ID annotation).

       -o <f> Direct the summary output to file <f>, rather than to stdout.

       -O <f> After  each  model  is  constructed,  resave  annotated,  possibly  modified source
              alignments to a file <f> in Stockholm format.  The alignments are annotated with  a
              reference  annotation line indicating which columns were assigned as consensus, and
              sequences are annotated with what relative sequence  weights  were  assigned.  Some
              residues  of the alignment may have been shifted to accommodate restrictions of the
              Plan7 profile architecture, which disallows transitions between insert  and  delete


       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.

              Specify that all sequences in msafile are proteins.

       --dna  Specify that all sequences in msafile are DNAs.

       --rna  Specify that all sequences in msafile are RNAs.


       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 <x>
              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 <x>
              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  range  of  a
              sequence  in  the  alignment (the number of alignment columns between the first and
              last positions of the sequence) 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 upweight 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].

              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  relative  weight

              No relative weights. All sequences are assigned uniform weight.

       --wid <x>
              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 number 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.

              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.

              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 <x>
              Explicitly set the effective sequence number for all models to <x>.

       --ere <x>
              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 <x>
              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 <x>
              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.

              Don't   use  any  priors.  Probability  parameters  will  simply  be  the  observed
              frequencies, after relative sequence weighting.

              Use a Laplace +1 prior in place of the default mixture Dirichlet prior.


       The location parameters for the  expected  score  distributions  for  MSV  filter  scores,
       Viterbi filter scores, and Forward scores require three short random sequence simulations.

       --EmL <n>
              Sets the sequence length in simulation that estimates the location parameter mu for
              MSV filter E-values. Default is 200.

       --EmN <n>
              Sets the number of sequences in simulation that estimates the location parameter mu
              for MSV filter E-values. Default is 200.

       --EvL <n>
              Sets the sequence length in simulation that estimates the location parameter mu for
              Viterbi filter E-values. Default is 200.

       --EvN <n>
              Sets the number of sequences in simulation that estimates the location parameter mu
              for Viterbi filter E-values. Default is 200.

       --EfL <n>
              Sets  the  sequence  length in simulation that estimates the location parameter tau
              for Forward E-values. Default is 100.

       --EfN <n>
              Sets the number of sequences in simulation that estimates  the  location  parameter
              tau for Forward E-values. Default is 200.

       --Eft <x>
              Sets  the  tail  mass fraction to fit in the simulation that estimates the location
              parameter tau for Forward evalues. Default is 0.04.


       --cpu <n>
              Set the number of parallel worker threads to <n>.  By default, HMMER sets  this  to
              the  number of CPU cores it detects in your machine - that is, it tries to maximize
              the use of your available processor cores. Setting <n> higher than  the  number  of
              available  cores is of little if any value, but you may want to set it to something
              less. You can  also  control  this  number  by  setting  an  environment  variable,

              This  option  is  only  available if HMMER was compiled with POSIX threads support.
              This is the default, but it may have been turned off for your site or  machine  for
              some reason.

       --informat <s>
              Declare  that  the input msafile is in format <s>.  Currently the accepted multiple
              alignment sequence file formats include Stockholm,  Aligned  FASTA,  Clustal,  NCBI
              PSI-BLAST,  PHYLIP, Selex, and UCSC SAM A2M. Default is to autodetect the format of
              the file.

       --seed <n>
              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.  The default
              seed is 42.

       --w_beta <x>
              Window length tail mass.  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.

       --w_length <n>
              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).

       --mpi  Run  as a parallel MPI program. Each alignment is assigned to a MPI worker node for
              construction. (Therefore, the maximum parallelization cannot exceed the  number  of
              alignments  in  the  input  msafile.)   This  is useful when building large profile
              libraries. This option is only available if optional MPI capability was enabled  at

              For  debugging  MPI  parallelization:  arrest  program  execution immediately after
              start, and wait for a debugger to attach to the running  process  and  release  the

       --maxinsertlen <n>
              Restrict  insert  length  parameterization  such that the expected insert length at
              each position of the model is no more than <n>.


       See hmmer(1) for a master man page with a  list  of  all  the  individual  man  pages  for
       programs in the HMMER package.

       For  complete  documentation,  see  the  user guide that came with your HMMER distribution
       (Userguide.pdf); or see the HMMER web page ().


       Copyright (C) 2015 Howard Hughes Medical Institute.
       Freely distributed under the GNU General Public License (GPLv3).

       For additional information on copyright and licensing, see the file  called  COPYRIGHT  in
       your HMMER source distribution, or see the HMMER web page ().


       Eddy/Rivas Laboratory
       Janelia Farm Research Campus
       19700 Helix Drive
       Ashburn VA 20147 USA