hmmsearch - Online in the Cloud

PROGRAM:

NAME

hmmsearch - search profile(s) against a sequence database

SYNOPSIS

hmmsearch [options] <hmmfile> <seqdb>

DESCRIPTION

hmmsearch is used to search one or more profiles against a sequence database. For each
profile in <hmmfile>, use that query profile to search the target database of sequences in
<seqdb>, and output ranked lists of the sequences with the most significant matches to the
profile. To build profiles from multiple alignments, see hmmbuild.

Either the query <hmmfile> or the target <seqdb> may be '-' (a dash character), in which
case the query profile or target database input will be read from a <stdin> pipe instead
of from a file. Only one input source can come through <stdin>, not both. An exception is
that if the <hmmfile> contains more than one profile query, then <seqdb> cannot come from
<stdin>, because we can't rewind the streaming target database to search it with another
profile.

The output format is designed to be human-readable, but is often so voluminous that
reading it is impractical, and parsing it is a pain. The --tblout and --domtblout options
save output in simple tabular formats that are concise and easier to parse. The -o option
allows redirecting the main output, including throwing it away in /dev/null.

OPTIONS

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

OPTIONS FOR CONTROLLING OUTPUT

-o <f> Direct the main human-readable output to a file <f> instead of the default stdout.

-A <f> Save a multiple alignment of all significant hits (those satisfying inclusion
thresholds) to the file <f>.

--tblout <f>
Save a simple tabular (space-delimited) file summarizing the per-target output,
with one data line per homologous target sequence found.

--domtblout <f>
Save a simple tabular (space-delimited) file summarizing the per-domain output,
with one data line per homologous domain detected in a query sequence for each
homologous model.

--acc Use accessions instead of names in the main output, where available for profiles
and/or sequences.

--noali
Omit the alignment section from the main output. This can greatly reduce the output
volume.

--notextw
Unlimit the length of each line in the main output. The default is a limit of 120
characters per line, which helps in displaying the output cleanly on terminals and
in editors, but can truncate target profile description lines.

--textw <n>
Set the main output's line length limit to <n> characters per line. The default is
120.

OPTIONS CONTROLLING REPORTING THRESHOLDS

Reporting thresholds control which hits are reported in output files (the main output,
--tblout, and --domtblout). Sequence hits and domain hits are ranked by statistical
significance (E-value) and output is generated in two sections called per-target and per-
domain output. In per-target output, by default, all sequence hits with an E-value <= 10
are reported. In the per-domain output, for each target that has passed per-target
reporting thresholds, all domains satisfying per-domain reporting thresholds are reported.
By default, these are domains with conditional E-values of <= 10. The following options
allow you to change the default E-value reporting thresholds, or to use bit score
thresholds instead.

-E <x> In the per-target output, report target sequences with an E-value of <= <x>. The
default is 10.0, meaning that on average, about 10 false positives will be reported
per query, so you can see the top of the noise and decide for yourself if it's
really noise.

-T <x> Instead of thresholding per-profile output on E-value, instead report target
sequences with a bit score of >= <x>.

--domE <x>
In the per-domain output, for target sequences that have already satisfied the per-
profile reporting threshold, report individual domains with a conditional E-value
of <= <x>. The default is 10.0. A conditional E-value means the expected number
of additional false positive domains in the smaller search space of those
comparisons that already satisfied the per-target reporting threshold (and thus
must have at least one homologous domain already).

--domT <x>
Instead of thresholding per-domain output on E-value, instead report domains with a
bit score of >= <x>.

OPTIONS FOR INCLUSION THRESHOLDS

Inclusion thresholds are stricter than reporting thresholds. Inclusion thresholds control
which hits are considered to be reliable enough to be included in an output alignment or a
subsequent search round, or marked as significant ("!") as opposed to questionable ("?")
in domain output.

--incE <x>
Use an E-value of <= <x> as the per-target inclusion threshold. The default is
0.01, meaning that on average, about 1 false positive would be expected in every
100 searches with different query sequences.

--incT <x>
Instead of using E-values for setting the inclusion threshold, instead use a bit
score of >= <x> as the per-target inclusion threshold. By default this option is
unset.

--incdomE <x>
Use a conditional E-value of <= <x> as the per-domain inclusion threshold, in
targets that have already satisfied the overall per-target inclusion threshold.
The default is 0.01.

--incdomT <x>
Instead of using E-values, use a bit score of >= <x> as the per-domain inclusion
threshold.

OPTIONS FOR MODEL-SPECIFIC SCORE THRESHOLDING

Curated profile databases may define specific bit score thresholds for each profile,
superseding any thresholding based on statistical significance alone.

To use these options, the profile must contain the appropriate (GA, TC, and/or NC)
optional score threshold annotation; this is picked up by hmmbuild from Stockholm format
alignment files. Each thresholding option has two scores: the per-sequence threshold <x1>
and the per-domain threshold <x2> These act as if -T<x1> --incT<x1> --domT<x2>
--incdomT<x2> has been applied specifically using each model's curated thresholds.

--cut_ga
Use the GA (gathering) bit scores in the model to set per-sequence (GA1) and per-
domain (GA2) reporting and inclusion thresholds. GA thresholds are generally
considered to be the reliable curated thresholds defining family membership; for
example, in Pfam, these thresholds define what gets included in Pfam Full
alignments based on searches with Pfam Seed models.

--cut_nc
Use the NC (noise cutoff) bit score thresholds in the model to set per-sequence
(NC1) and per-domain (NC2) reporting and inclusion thresholds. NC thresholds are
generally considered to be the score of the highest-scoring known false positive.

--cut_tc
Use the TC (trusted cutoff) bit score thresholds in the model to set per-sequence
(TC1) and per-domain (TC2) reporting and inclusion thresholds. TC thresholds are
generally considered to be the score of the lowest-scoring known true positive that
is above all known false positives.

OPTIONS CONTROLLING THE ACCELERATION PIPELINE

HMMER3 searches are accelerated in a three-step filter pipeline: the MSV filter, the
Viterbi filter, and the Forward filter. The first filter is the fastest and most
approximate; the last is the full Forward scoring algorithm. There is also a bias filter
step between MSV and Viterbi. Targets that pass all the steps in the acceleration pipeline
are then subjected to postprocessing -- domain identification and scoring using the
Forward/Backward algorithm.

Changing filter thresholds only removes or includes targets from consideration; changing
filter thresholds does not alter bit scores, E-values, or alignments, all of which are
determined solely in postprocessing.

--max Turn off all filters, including the bias filter, and run full Forward/Backward
postprocessing on every target. This increases sensitivity somewhat, at a large
cost in speed.

--F1 <x>
Set the P-value threshold for the MSV filter step. The default is 0.02, meaning
that roughly 2% of the highest scoring nonhomologous targets are expected to pass
the filter.

--F2 <x>
Set the P-value threshold for the Viterbi filter step. The default is 0.001.

--F3 <x>
Set the P-value threshold for the Forward filter step. The default is 1e-5.

--nobias
Turn off the bias filter. This increases sensitivity somewhat, but can come at a
high cost in speed, especially if the query has biased residue composition (such as
a repetitive sequence region, or if it is a membrane protein with large regions of
hydrophobicity). Without the bias filter, too many sequences may pass the filter
with biased queries, leading to slower than expected performance as the
computationally intensive Forward/Backward algorithms shoulder an abnormally heavy
load.

OTHER OPTIONS

--nonull2
Turn off the null2 score corrections for biased composition.

-Z <x> Assert that the total number of targets in your searches is <x>, for the purposes
of per-sequence E-value calculations, rather than the actual number of targets
seen.

--domZ <x>
Assert that the total number of targets in your searches is <x>, for the purposes
of per-domain conditional E-value calculations, rather than the number of targets
that passed the reporting thresholds.

--seed <n>
Set the random number seed to <n>. Some steps in postprocessing require Monte
Carlo simulation. The default is to use a fixed seed (42), so that results are
exactly reproducible. Any other positive integer will give different (but also
reproducible) results. A choice of 0 uses a randomly chosen seed.

--tformat <s>
Assert that the target sequence database file is in format <s>. Accepted formats
include fasta, embl, genbank, ddbj, uniprot, stockholm, pfam, a2m, and afa. The
default is to autodetect the format of the file.

--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,
HMMER_NCPU.

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

--stall
For debugging the MPI master/worker version: pause after start, to enable the
developer to attach debuggers to the running master and worker(s) processes. Send
SIGCONT signal to release the pause. (Under gdb: (gdb) signal SIGCONT) (Only
available if optional MPI support was enabled at compile-time.)

--mpi Run in MPI master/worker mode, using mpirun. (Only available if optional MPI
support was enabled at compile-time.)

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