Provided by: infernal_1.1.2-2_amd64 bug

NAME

       cmsearch - search covariance model(s) against a sequence database

SYNOPSIS

       cmsearch [options] <cmfile> <seqdb>

DESCRIPTION

       cmsearch  is  used  to  search  one  or  more  covariance  models (CMs) against a sequence
       database.  For each CM in <cmfile>, use that query CM to search  the  target  database  of
       sequences  in  <seqdb>, and output ranked lists of the sequences with the most significant
       matches to the CM.  To build CMs from multiple alignments, see cmbuild.

       The query <cmfile> must have been calibrated for E-values with cmcalibrate.  As a  special
       exception,  any  models  in  <cmfile> that have zero basepairs need not be calibrated. For
       these models, profile HMM search algorithms will be used instead of CM ones, as  discussed
       further below.

       The query <cmfile> may be '-' (a dash character), in which case the query CM input will be
       read from a <stdin> pipe instead of from a file. The <seqdb> may not be  '-'  because  the
       current implementation needs to be able to rewind the database, which is not possible with
       stdin input.

       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 option saves output in a
       simple tabular format that  is  concise  and  easier  to  parse.   The  -o  option  allows
       redirecting the main output, including throwing it away in /dev/null.

       cmsearch reexamines the 5' and 3' termini of target sequences using specialized algorithms
       for detection of truncated hits, in which part of the 5' and/or 3' end of the actual  full
       length  homologous  sequence  is  missing in the target sequence file. These types of hits
       will be most common in sequence files  consisting  of  unassembled  sequencing  reads.  By
       default,  any  5'  truncated  hit  is  required to include the first residue of the target
       sequence it derives from in <seqdb>, and any 3' truncated hit is required to  include  the
       final  residue  of  the  target sequence it derives from. Any 5' and 3' truncated hit must
       include the first and final residue of the target sequence it derives from. The --anytrunc
       option  will relax the requirements for hit inclusion of sequence endpoints, and truncated
       hits are allowed to start and stop at  any  positions  of  target  sequences.  Importantly
       though, with --anytrunc, hit E-values will be less accurate because model calibration does
       not consider the possibility of truncated hits, so use it  with  caution.   The  --notrunc
       option can be used to turn off truncated hit detection.  --notrunc will reduce the running
       time of cmsearch, most significantly for target <seqdb>  files  that  include  many  short
       sequences.

       Truncated  hit  detection  is  automatically turned off when the --max, --nohmm, --qdb, or
       --nonbanded options are used because it relies on the use of  an  accelerated  HMM  banded
       alignment strategy that is turned off by any of those options.

OPTIONS

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

       -g     Turn  on the glocal alignment algorithm, global with respect to the query model and
              local with respect  to  the  target  database.  By  default,  the  local  alignment
              algorithm  is  used which is local with respect to both the target sequence and the
              model. In local mode, the alignment to span two or more subsequences  if  necessary
              (e.g.  if  the structures of the query model and target sequence are only partially
              shared), allowing certain large insertions and deletions in  the  structure  to  be
              penalized  differently  than normal indels. Local mode performs better on empirical
              benchmarks and is significantly  more  sensitive  for  remote  homology  detection.
              Empirically,  glocal searches return many fewer hits than local searches, so glocal
              may be desired for some applications. With -g, all models must be calibrated,  even
              those with zero basepairs.

       -Z <x> Calculate  E-values as if the search space size was <x> megabases (Mb). Without the
              use of this option, the search space  size  is  defined  as  the  total  number  of
              nucleotides  in  <seqdb> times 2, because both strands of each target sequence will
              be searched.

       --devhelp
              Print help, as with -h , but also include expert options  that  are  not  displayed
              with  -h  .   These  expert  options  are  not expected to be relevant for the vast
              majority of users and so are not described in the manual page.  The only  resources
              for  understanding what they actually do are the brief one-line descriptions output
              when --devhelp is enabled, and the source code.

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 hits found, with one
              data line per hit. The format of this  file  is  described  in  section  6  of  the
              Infernal user guide.

       --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.

       --verbose
              Include extra search pipeline statistics  in  the  main  output,  including  filter
              survival  statistics  for truncated hit detection and number of envelopes discarded
              due to matrix size overflows.

OPTIONS CONTROLLING REPORTING THRESHOLDS

       Reporting thresholds control which hits are reported in output files (the main output  and
       --tblout)  Hits  are  ranked  by statistical significance (E-value).  By default, all hits
       with an E-value <= 10 are reported.  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-CM output on E-value, report target  sequences  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
       in  a  possible  subsequent  search  round,  or  marked as significant ("!") as opposed to
       questionable ("?") in hit output.

       --incE <x>
              Use an E-value of <= <x> as the hit 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 hit inclusion threshold.  By default this option is unset.

OPTIONS FOR MODEL-SPECIFIC SCORE THRESHOLDING

       Curated CM databases may define specific bit score thresholds for each CM, 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 cmbuild from Stockholm format
       alignment files. Each thresholding option has a score of <x> bits, and acts as if  -T  <x>
       --incT <x> has been applied specifically using each model's curated thresholds.

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

       --cut_nc
              Use  the  NC  (noise cutoff) bit score thresholds in the model to set hit 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 hit 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

       Infernal  1.1  searches  are  accelerated  in  a six-stage filter pipeline. The first five
       stages use a profile HMM to define envelopes that are passed  to  the  stage  six  CM  CYK
       filter.  Any envelopes that survive all filters are assigned final scores using the the CM
       Inside algorithm. (See the user guide for more information.)

       The profile HMM filter is built by the cmbuild program and is stored in <cmfile>.

       Each  successive  filter  is  slower  than  the  previous  one,  but  better  than  it  at
       disciminating between subsequences that may contain high-scoring CM hits and those that do
       not. The first three HMM filter stages are the same as those used in HMMER3.  Stage 1 (F1)
       is  the  local  HMM  SSV filter modified for long sequences. Stage 2 (F2) is the local HMM
       Viterbi filter. Stage 3 (F3) is the local HMM Forward filter.  Each  of  the  first  three
       stages  uses  the profile HMM in local mode, which allows a target subsequence to align to
       any region of the HMM. Stage 4 (F4) is a  glocal  HMM  filter,  which  requires  a  target
       subsequence  to  align  to  the  full-length  profile  HMM. Stage 5 (F5) is the glocal HMM
       envelope definition filter, which uses HMMER3's domain identification heursitics to define
       envelope  boundaries.  After each stage from 2 to 5 a bias filter step (F2b, F3b, F4b, and
       F5b) is used to remove sequences that appear to have  passed  the  filter  due  to  biased
       composition  alone.  Any envelopes that survive stages F1 through F5b are then passed with
       the local CM CYK filter. The CYK filter uses  constraints  (bands)  derived  from  an  HMM
       alignment  of  the  envelope  to reduce the number of required calculations and save time.
       Any envelopes that pass CYK are scored with the local CM Inside algorithm, again using HMM
       bands for acceleration.

       The  default filter thresholds that define the minimum score required for a subsequence to
       survive each stage are defined based on the size of the database in <seqdb> (or  the  size
       <x> in megabases (Mb) specified by the -Z <x> or --FZ <x> options).  For larger databases,
       the filters are more strict leading to more acceleration but potentially a greater loss of
       sensitivity.  The  rationale is that for larger databases, hits must have higher scores to
       achieve statistical  significance,  so  stricter  filtering  that  removes  lower  scoring
       insignificant hits is acceptable.

       The  P-value  thresholds  for  all  possible  search space sizes and all filter stages are
       listed next. (A P-value threshold of 0.01 means that roughly 1%  of  the  highest  scoring
       nonhomologous  subsequence are expected to pass the filter.) Z is defined as the number of
       nucleotides in the complete target sequence file times 2  because  both  strands  will  be
       searched with each model.

       If  Z is less than 2 Mb: F1 is 0.35; F2 and F2b are off; F3, F3b, F4, F4b and F5 are 0.02;
       F6 is 0.0001.

       If Z is between 2 Mb and 20 Mb: F1 is 0.35; F2 and F2b are off; F3, F3b, F4,  F4b  and  F5
       are 0.005; F6 is 0.0001.

       If Z is between 20 Mb and 200 Mb: F1 is 0.35; F2 and F2b are 0.15; F3, F3b, F4, F4b and F5
       are 0.003; F6 is 0.0001.

       If Z is between 200 Mb and 2 Gb: F1 is 0.15; F2 and F2b are 0.15; F3, F3b,  F4,  F4b,  F5,
       and F5b are 0.0008; and F6 is 0.0001.

       If Z is between 2 Gb and 20 Gb: F1 is 0.15; F2 and F2b are 0.15; F3, F3b, F4, F4b, F5, and
       F5b are 0.0002; and F6 is 0.0001.

       If Z is more than 20 Gb: F1 is 0.06; F2 and F2b are 0.02; F3, F3b, F4, F4b,  F5,  and  F5b
       are 0.0002; and F6 is 0.0001.

       These  thresholds  were  chosen based on performance on an internal benchmark testing many
       different possible settings.

       There are five options for controlling the general filtering level. These options are,  in
       order  from  least  strict  (slowest but most sensitive) to most strict (fastest but least
       sensitive): --max, --nohmm, --mid, --default, (this is the default setting), --rfam.   and
       --hmmonly.   With --default the filter thresholds will be database-size dependent. See the
       explanation of each of these individual options below for more information.

       Additionally, an expert user can precisely control each filter stage score threshold  with
       the  --F1, --F1b, --F2, --F2b, --F3, --F3b, --F4, --F4b, --F5, --F5b, and --F6 options. As
       well as turn each stage on or off with  the  --noF1,  --doF1b,  --noF2,  --noF2b,  --noF3,
       --noF3b,  --noF4, --noF4b, --noF5, and --noF6.  options.  These options are only displayed
       if the --devhelp option  is  used  to  keep  the  number  of  displayed  options  with  -h
       reasonable, and because they are only expected to be useful to a small minority of users.

       As  a  special  case,  for  any  models in <cmfile> which have zero basepairs, profile HMM
       searches are run instead of CM  searches.  HMM  algorithms  are  more  efficient  than  CM
       algorithms,  and  the  benefit  of  CM  algorithms  is  lost  for models with no secondary
       structure (zero basepairs). These profile HMM searches will run significantly faster  than
       the  CM  searches.  You  can  force  HMM-only searches with the --hmmonly option. For more
       information on HMM-only searches see the description of the --hmmonly  option  below,  and
       the user guide.

       --max  Turn  off  all  filters,  and  run  non-banded  Inside  on every full-length target
              sequence. This increases sensitivity somewhat, at an extremely large cost in speed.

       --nohmm
              Turn off all HMM filter stages (F1 through F5b). The CYK filter, using  QDBs,  will
              be run on every full-length target sequence and will enforce a P-value threshold of
              0.0001. Each subsequence that survives CYK will be passed  to  Inside,  which  will
              also  use  QDBs  (but a looser set). This increases sensitivity somewhat, at a very
              large cost in speed.

       --mid  Turn off the HMM SSV and Viterbi filter stages (F1 through F2b).  Set remaining HMM
              filter  thresholds  (F3 through F5b) to 0.02 by default, but changeable to <x> with
              --Fmid <x> sequence. This may increase sensitivity, at a significant cost in speed.

       --default
              Use the default filtering strategy. This  option  is  on  by  default.  The  filter
              thresholds are determined based on the database size.

       --rfam Use a strict filtering strategy devised for large databases (more than 20 Gb). This
              will accelerate the search at a potential cost to  sensitivity.  It  will  have  no
              effect if the database is larger than 20 Gb.

       --hmmonly
              Only  use  the  filter  profile  HMM  for searches, do not use the CM.  Only filter
              stages F1 through F3 will be executed, using strict P-value  thresholds  (0.02  for
              F1,  0.001  for  F2 and 0.00001 for F3).  Additionally a bias composition filter is
              used after the F1 stage (with P=0.02 survival threshold).  Any  hit  that  survives
              all  stages  and has an HMM E-value or bit score above the reporting threshold will
              be output.  The user can change the HMM-only filter  thresholds  and  options  with
              --hmmF1,  --hmmF2,  --hmmF3,  --hmmnobias, --hmmnonull2, and --hmmmax.  By default,
              searches for any model with zero basepairs will be run in HMM-only mode.  This  can
              be  turned  off,  forcing CM searches for these models with the --nohmmonly option.
              These options are only displayed if the --devhelp option is used.

       --FZ <x>
              Set filter thresholds as the defaults used if the database were <x> megabases (Mb).
              If  used  with  <x>  greater  than 20000 (20 Gb) this option has the same effect as
              --rfam.

       --Fmid <x>
              With the --mid option set the HMM filter thresholds (F3 through F5b)  to  <x>.   By
              default, <x> is 0.02.

OTHER OPTIONS

       --notrunc
              Turn off truncated hit detection.

       --anytrunc
              Allow  truncated  hits  to  begin  and end at any position in a target sequence. By
              default, 5' truncated hits must include the first residue of their target  sequence
              and 3' truncated hits must include the final residue of their target sequence. With
              this option you may observe fewer full length hits that extend to the beginning and
              end of the query CM.

       --nonull3
              Turn  off the null3 CM score corrections for biased composition. This correction is
              not used during the HMM filter stages.

       --mxsize <x>
              Set the maximum allowable CM DP matrix size to <x> megabytes. By default this  size
              is  128  Mb.   This  should  be  large  enough  for  the vast majority of searches,
              especially with smaller models.  If cmsearch encounters an envelope in the  CYK  or
              Inside  stage  that  requires a larger matrix, the envelope will be discounted from
              consideration. This behavior is like an additional filter that  prevents  expensive
              (slow)  CM  DP  calculations, but at a potential cost to sensitivity.  Note that if
              cmsearch is being run in <n> multiple threads on  a  multicore  machine  then  each
              thread may have an allocated matrix of up to size <x> Mb at any given time.

       --smxsize <x>
              Set  the  maximum  allowable  CM search DP matrix size to <x> megabytes. By default
              this size is 128 Mb.  This option is only relevant if  the  CM  will  not  use  HMM
              banded  matrices,  i.e.  if  the  --max,  --nohmm,  --qdb,  --fqdb, --nonbanded, or
              --fnonbanded options are also used. Note that if  cmsearch  is  being  run  in  <n>
              multiple  threads  on  a  multicore  machine then each thread may have an allocated
              matrix of up to size <x> Mb at any given time.

       --cyk  Use the CYK algorithm, not Inside, to determine the final score of all hits.

       --acyk Use the CYK algorithm to align hits. By default, the Durbin/Holmes optimal accuracy
              algorithm  is  used, which finds the alignment that maximizes the expected accuracy
              of all aligned residues.

       --wcx <x>
              For each CM, set the W parameter, the expected maximum length  of  a  hit,  to  <x>
              times  the  consensus length of the model. By default, the W parameter is read from
              the CM file and was calculated based on the transition probabilities of  the  model
              by cmbuild.  You can find out what the default W is for a model using cmstat.  This
              option should be used with caution as it impacts the filtering pipeline at  several
              different  stages  in  nonobvious  ways.  It  is  only recommended for expert users
              searching for hits that are much longer than any of the homologs used to build  the
              model  in  cmbuild,  e.g.  ones with large introns or other large insertions.  This
              option cannot be used in combination with the  --nohmm,  --fqdb  or  --qdb  options
              because in those cases W is limited by query-dependent bands.

       --toponly
              Only  search  the  top (Watson) strand of target sequences in <seqdb>.  By default,
              both strands are searched. This will halve the database size (Z).

       --bottomonly
              Only search the bottom (Crick) strand of target sequences in <seqdb>.  By  default,
              both strands are searched.  This will halve the database size (Z).

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

       --cpu <n>
              Set  the  number of parallel worker threads to <n>.  By default, Infernal 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, INFERNAL_NCPU.  This option is only available if  Infernal  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.  To use --mpi, the sequence file must
              have first been 'indexed' using the esl-sfetch  program,  which  is  included  with
              Infernal,  in  the  easel/miniapps/  subdirectory.  (Only available if optional MPI
              support was enabled at compile-time.)

SEE ALSO

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

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

COPYRIGHT

       Copyright (C) 2016 Howard Hughes Medical Institute.
       Freely distributed under a BSD open source license.

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

AUTHOR

       The Eddy/Rivas Laboratory
       Janelia Farm Research Campus
       19700 Helix Drive
       Ashburn VA 20147 USA
       http://eddylab.org