hhblits1
Fast homology detection method to iteratively search a hmm database
Usage
hhblits -i
query
[options]
Overview
HHblits 3.3.0: HMM-HMM-based lightning-fast iterative sequence search HHblits is a sensitive, general-purpose, iterative sequence search tool that represents both query and database sequences by HMMs. You can search HHblits databases starting with a single query sequence, a multiple sequence alignment (MSA), or an HMM. HHblits prints out a ranked list of database HMMs/MSAs and can also generate an MSA by merging the significant database HMMs/MSAs onto the query MSA.
Steinegger M, Meier M, Mirdita M, V??hringer H, Haunsberger S J, and S??ding J (2019) HH-suite3 for fast remote homology detection and deep protein annotation. BMC Bioinformatics, doi:10.1186/s12859-019-3019-7 (c) The HH-suite development team
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-i <file> -
input/query: single sequence or multiple sequence alignment (MSA) in a3m, a2m, or FASTA format, or HMM in hhm format
<file> may be 'stdin' or 'stdout' throughout.
Options
-
-d <name> -
database name (e.g. uniprot20_29Feb2012) Multiple databases may be specified with '-d <db1>
-d<db2> ...'
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-n -
[1,8] number of iterations (default=2)
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-e -
[0,1] E-value cutoff for inclusion in result alignment (def=0.001)
Input alignment format:
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-M a2m -
use A2M/A3M (default): upper case = Match; lower case = Insert;
-
' -' = Delete; '.' = gaps aligned to inserts (may be omitted)
-
-M first -
use FASTA: columns with residue in 1st sequence are match states
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-M [0,100] -
use FASTA: columns with fewer than X% gaps are match states
-tags/-notags-
do NOT / do neutralize His-, C-myc-, FLAG-tags, and trypsin recognition sequence to background distribution (def=-notags)
Output options:
-
-o <file> -
write results in standard format to file (default=<infile.hhr>)
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-oa3m <file> -
write result MSA with significant matches in a3m format
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-opsi <file> -
write result MSA of significant matches in PSI-BLAST format
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-ohhm <file> -
write HHM file for result MSA of significant matches
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-oalis <name> -
write MSAs in A3M format after each iteration
-blasttab <name> write result in tabular BLAST format (compatible to -m 8 or -outfmt 6 output)
1
|
2 3 4 5 6 8 9 10 11 12 |
|---|---|
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'query target #match/tLen #mismatch #gapOpen qstart qend tstart tend eval score' |
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-add_cons -
generate consensus sequence as master sequence of query MSA (default=don't)
-
-hide_cons -
don't show consensus sequence in alignments (default=show)
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-hide_pred -
don't show predicted 2ndary structure in alignments (default=show)
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-hide_dssp -
don't show DSSP 2ndary structure in alignments (default=show)
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-show_ssconf -
show confidences for predicted 2ndary structure in alignments
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-Ofas <file> -
write pairwise alignments in FASTA xor A2M (
-Oa2m) xor A3M (-Oa3m) format
-
-seq <int> -
max. number of query/template sequences displayed (default=1)
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-aliw <int> -
number of columns per line in alignment list (default=80)
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-p [0,100] -
minimum probability in summary and alignment list (default=20)
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-E [0,inf[ -
maximum E-value in summary and alignment list (default=1E+06)
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-Z <int> -
maximum number of lines in summary hit list (default=500)
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-z <int> -
minimum number of lines in summary hit list (default=10)
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-B <int> -
maximum number of alignments in alignment list (default=500)
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-b <int> -
minimum number of alignments in alignment list (default=10)
Prefilter options
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-noprefilt -
disable all filter steps
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-noaddfilter -
disable all filter steps (except for fast prefiltering)
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-maxfilt -
max number of hits allowed to pass 2nd prefilter (default=20000)
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-min_prefilter_hits -
min number of hits to pass prefilter (default=100)
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-prepre_smax_thresh -
min score threshold of ungapped prefilter (default=10)
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-pre_evalue_thresh -
max E-value threshold of Smith-Waterman prefilter score (default=1000.0)
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-pre_bitfactor -
prefilter scores are in units of 1 bit / pre_bitfactor (default=4)
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-pre_gap_open -
gap open penalty in prefilter Smith-Waterman alignment (default=20)
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-pre_gap_extend -
gap extend penalty in prefilter Smith-Waterman alignment (default=4)
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-pre_score_offset -
offset on sequence profile scores in prefilter S-W alignment (default=50)
Filter options applied to query MSA, database MSAs, and result MSA
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-all -
show all sequences in result MSA; do not filter result MSA
-interim_filter NONE|FULL
-
filter sequences of query MSA during merging to avoid early stop (default: FULL)
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NONE: disables the intermediate filter FULL: if an early stop occurs compare filter seqs in an all vs. all comparison
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-id -
[0,100] maximum pairwise sequence identity (def=90)
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-diff [0,inf[ -
filter MSAs by selecting most diverse set of sequences, keeping at least this many seqs in each MSA block of length 50 Zero and non-numerical values turn off the filtering. (def=1000)
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-cov -
[0,100] minimum coverage with master sequence (%) (def=0)
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-qid -
[0,100] minimum sequence identity with master sequence (%) (def=0)
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-qsc -
[0,100] minimum score per column with master sequence (default=-20.0)
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-neff [1,inf] -
target diversity of multiple sequence alignment (default=off)
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-mark -
do not filter out sequences marked by ">@"in their name line
HMM-HMM alignment options:
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-norealign -
do NOT realign displayed hits with MAC algorithm (def=realign)
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-realign_old_hits -
realign hits from previous iterations
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-mact [0,1[ -
posterior prob threshold for MAC realignment controlling greediness at alignment ends: 0:global >0.1:local (default=0.35)
-glob/-loc-
use global/local alignment mode for searching/ranking (def=local)
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-realign -
realign displayed hits with max. accuracy (MAC) algorithm
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-realign_max <int> -
realign max. <int> hits (default=500)
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-ovlp <int> -
banded alignment: forbid <ovlp> largest diagonals |i-j| of DP matrix (def=0)
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-alt <int> -
show up to this many alternative alignments with raw score > smin(def=4)
-premerge <int> merge <int> hits to query MSA before aligning remaining hits (def=3)
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-smin <float> -
minimum raw score for alternative alignments (def=20.0)
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-shift [-1,1] -
profile-profile score offset (def=-0.03)
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-corr [0,1] -
weight of term for pair correlations (def=0.10)
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-sc -
<int> amino acid score (tja: template HMM at column j) (def=1)
0
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= log2 Sum(tja*qia/pa) (pa: aa background frequencies) |
|---|---|
1
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= log2 Sum(tja*qia/pqa) (pqa = 1/2*(pa+ta) ) |
2
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= log2 Sum(tja*qia/ta) (ta: av. aa freqs in template) |
3
|
= log2 Sum(tja*qia/qa) (qa: av. aa freqs in query) |
5
|
local amino acid composition correction |
-
-ssm {0,..,4} -
0: no ss scoring 1,2: ss scoring after or during alignment [default=2] 3,4: ss scoring after or during alignment, predicted vs. predicted
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-ssw [0,1] -
weight of ss score (def=0.11)
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-ssa [0,1] -
ss confusion matrix = (1-ssa)*I + ssa*psipred-confusion-matrix [def=1.00)
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-wg -
use global sequence weighting for realignment!
Gap cost options:
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-gapb [0,inf[ -
Transition pseudocount admixture (def=1.00)
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-gapd [0,inf[ -
Transition pseudocount admixture for open gap (default=0.15)
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-gape [0,1.5] -
Transition pseudocount admixture for extend gap (def=1.00)
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-gapf ]0,inf] -
factor to increase/reduce gap open penalty for deletes (def=0.60)
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-gapg ]0,inf] -
factor to increase/reduce gap open penalty for inserts (def=0.60)
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-gaph ]0,inf] -
factor to increase/reduce gap extend penalty for deletes(def=0.60)
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-gapi ]0,inf] -
factor to increase/reduce gap extend penalty for inserts(def=0.60)
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-egq -
[0,inf[ penalty (bits) for end gaps aligned to query residues (def=0.00)
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-egt -
[0,inf[ penalty (bits) for end gaps aligned to template residues (def=0.00)
Pseudocount (pc) options:
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Context specific hhm pseudocounts:
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-pc_hhm_contxt_mode {0,..,3} -
position dependence of pc admixture 'tau' (pc mode, default=2)
- 0: no pseudo counts:
-
tau = 0
- 1: constant
-
tau = a
-
2: diversity-dependent: tau = a/(1+((Neff[i]-1)/b)^c) 3: CSBlast admixture: tau = a(1+b)/(Neff[i]+b) (Neff[i]: number of effective seqs in local MSA around column i)
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-pc_hhm_contxt_a -
[0,1] overall pseudocount admixture (def=0.9)
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-pc_hhm_contxt_b -
[1,inf[ Neff threshold value for mode 2 (def=4.0)
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-pc_hhm_contxt_c -
[0,3] extinction exponent c for mode 2 (def=1.0)
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Context independent hhm pseudocounts (used for templates; used for query if contxt file is not available):
-
-pc_hhm_nocontxt_mode {0,..,3} -
position dependence of pc admixture 'tau' (pc mode, default=2)
- 0: no pseudo counts:
-
tau = 0
- 1: constant
-
tau = a
-
2: diversity-dependent: tau = a/(1+((Neff[i]-1)/b)^c) (Neff[i]: number of effective seqs in local MSA around column i)
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-pc_hhm_nocontxt_a -
[0,1] overall pseudocount admixture (def=1.0)
-
-pc_hhm_nocontxt_b -
[1,inf[ Neff threshold value for mode 2 (def=1.5)
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-pc_hhm_nocontxt_c -
[0,3] extinction exponent c for mode 2 (def=1.0)
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Context specific prefilter pseudocounts:
-
-pc_prefilter_contxt_mode {0,..,3} -
position dependence of pc admixture 'tau' (pc mode, default=3)
- 0: no pseudo counts:
-
tau = 0
- 1: constant
-
tau = a
-
2: diversity-dependent: tau = a/(1+((Neff[i]-1)/b)^c) 3: CSBlast admixture: tau = a(1+b)/(Neff[i]+b) (Neff[i]: number of effective seqs in local MSA around column i)
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-pc_prefilter_contxt_a -
[0,1] overall pseudocount admixture (def=0.8)
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-pc_prefilter_contxt_b -
[1,inf[ Neff threshold value for mode 2 (def=2.0)
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-pc_prefilter_contxt_c -
[0,3] extinction exponent c for mode 2 (def=1.0)
-
Context independent prefilter pseudocounts (used if context file is not available):
-
-pc_prefilter_nocontxt_mode {0,..,3} -
position dependence of pc admixture 'tau' (pc mode, default=2)
- 0: no pseudo counts:
-
tau = 0
- 1: constant
-
tau = a
-
2: diversity-dependent: tau = a/(1+((Neff[i]-1)/b)^c) (Neff[i]: number of effective seqs in local MSA around column i)
-
-pc_prefilter_nocontxt_a -
[0,1] overall pseudocount admixture (def=1.0)
-
-pc_prefilter_nocontxt_b -
[1,inf[ Neff threshold value for mode 2 (def=1.5)
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-pc_prefilter_nocontxt_c -
[0,3] extinction exponent c for mode 2 (def=1.0)
-
Context-specific pseudo-counts:
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-nocontxt -
use substitution-matrix instead of context-specific pseudocounts
-contxt <file> context file for computing context-specific pseudocounts (default=)
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-csw -
[0,inf] weight of central position in cs pseudocount mode (def=1.6)
-
-csb -
[0,1] weight decay parameter for positions in cs pc mode (def=0.9)
Other options:
-
-v <int> -
verbose mode: 0:no screen output 1:only warings 2: verbose (def=2)
-neffmax ]1,20] skip further search iterations when diversity Neff of query MSA
-
becomes larger than neffmax (default=20.0)
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-cpu <int> -
number of CPUs to use (for shared memory SMPs) (default=2)
-scores <file> write scores for all pairwise comparisons to file
-filter_matrices filter matrices for similarity to output at most 100 matrices
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-atab -
<file> write all alignments in tabular layout to file
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-maxseq <int> -
max number of input rows (def=65535)
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-maxres <int> -
max number of HMM columns (def=20001)
-maxmem [1,inf[ limit memory for realignment (in GB) (def=3.0)
Examples
hhblits -i query.fas -o query.hhr -d ./uniclust30
hhblits -i query.fas -o query.hhr -oa3m query.a3m -n 1 -d ./uniclust30
Download databases from <http://wwwuser.gwdg.de/~compbiol/data/hhsuite/databases/hhsuite_dbs/>.
Releases
7 releases since Debian 7 (Wheezy); the text changed 6 times.
-add_cons since Debian 9 (Stretch);
-corr since Debian 9 (Stretch);
-csb since Debian 9 (Stretch);
-csw since Debian 9 (Stretch);
-hide_cons since Debian 9 (Stretch);
-hide_dssp since Debian 9 (Stretch);
-hide_pred since Debian 9 (Stretch);
-mark since Debian 9 (Stretch);
-maxseq since Debian 11 (Bullseye);
-min_prefilter_hits since Debian 9 (Stretch);
-ovlp since Debian 9 (Stretch);
-pc_hhm_contxt_a since Debian 9 (Stretch);
-pc_hhm_contxt_b since Debian 9 (Stretch);
-pc_hhm_contxt_c since Debian 9 (Stretch);
-pc_hhm_contxt_mode since Debian 9 (Stretch);
-pc_hhm_nocontxt_a since Debian 9 (Stretch);
-pc_hhm_nocontxt_b since Debian 9 (Stretch);
-pc_hhm_nocontxt_c since Debian 9 (Stretch);
-pc_hhm_nocontxt_mode since Debian 9 (Stretch);
-pc_prefilter_contxt_a since Debian 9 (Stretch);
-pc_prefilter_contxt_b since Debian 9 (Stretch);
-pc_prefilter_contxt_c since Debian 9 (Stretch);
-pc_prefilter_contxt_mode since Debian 9 (Stretch);
-pc_prefilter_nocontxt_a since Debian 9 (Stretch);
-pc_prefilter_nocontxt_b since Debian 9 (Stretch);
-pc_prefilter_nocontxt_c since Debian 9 (Stretch);
-pc_prefilter_nocontxt_mode since Debian 9 (Stretch);
-pre_bitfactor since Debian 9 (Stretch);
-pre_evalue_thresh since Debian 9 (Stretch);
-pre_gap_extend since Debian 9 (Stretch);
-pre_gap_open since Debian 9 (Stretch);
-pre_score_offset since Debian 9 (Stretch);
-prepre_smax_thresh since Debian 9 (Stretch);
-realign since Debian 9 (Stretch);
-realign_old_hits since Debian 9 (Stretch);
-sc since Debian 9 (Stretch);
-show_ssconf since Debian 9 (Stretch);
-smin since Debian 9 (Stretch);
-ssa since Debian 9 (Stretch);
-wg since Debian 9 (Stretch).
-addss until Debian 8 (Jessie);
-cslib until Debian 8 (Jessie);
-nodbfilter until Debian 8 (Jessie);
-oa2m until Debian 7 (Wheezy);
-pca until Debian 8 (Jessie);
-pcb until Debian 8 (Jessie);
-pcc until Debian 8 (Jessie);
-pcm until Debian 8 (Jessie);
-pre_pca until Debian 8 (Jessie);
-psipred_data until Debian 8 (Jessie);
-qhhm until Debian 8 (Jessie).