--- name: "hhalign" section: "1" platform: "linux" package: "hhsuite" version: "3.3.0+ds-8+b3" release: "Debian 13 (Trixie)" platforms: ["linux"] url: "https://new.carta.tech/hhalign" --- # hhalign(1) align a query alignment/HMM to a template alignment/HMM ## NAME hhalign - align a query alignment/HMM to a template alignment/HMM ## SYNOPSIS **hhalign** *-i query -t template* \[*options*\] ## DESCRIPTION HHalign 3.3.0 Align a query alignment/HMM to a template alignment/HMM by HMM-HMM alignment If only one alignment/HMM is given it is compared to itself and the best off-diagonal alignment plus all further non-overlapping alignments above significance threshold are shown. 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 - **-i** \ input/query: single sequence or multiple sequence alignment (MSA) in a3m, a2m, or FASTA format, or HMM in hhm format - **-t** \ input/template: single sequence or multiple sequence alignment (MSA) in a3m, a2m, or FASTA format, or HMM in hhm format \ may be 'stdin' or 'stdout' throughout. ### Input alignment format: - **-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 - **-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** \ write results in standard format to file (default=\) - **-oa3m** \ write query alignment in a3m or PSI-BLAST format (**-opsi**) to file (default=none) - **-aa3m** \ append query alignment in a3m (**-aa3m**) or PSI-BLAST format (**-apsi** )to file (default=none) - **-Ofas** \ write pairwise alignments in FASTA xor A2M (**-Oa2m**) xor A3M (**-Oa3m**) format - **-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) - **-hide\_pred** don't show predicted 2ndary structure in alignments (default=show) - **-hide\_dssp** don't show DSSP 2ndary structure in alignments (default=show) - **-show\_ssconf** show confidences for predicted 2ndary structure in alignments - **-seq** \ max. number of query/template sequences displayed (default=1) - **-aliw** \ number of columns per line in alignment list (default=80) - **-p** \[0,100\] minimum probability in summary and alignment list (default=0) - **-E** \[0,inf\[ maximum E-value in summary and alignment list (default=1E+06) - **-Z** \ maximum number of lines in summary hit list (default=100) - **-z** \ minimum number of lines in summary hit list (default=1) - **-B** \ maximum number of alignments in alignment list (default=100) - **-b** \ minimum number of alignments in alignment list (default=1) Filter options applied to query MSA, template MSA, and result MSA - **-id** \[0,100\] maximum pairwise sequence identity (def=90) - **-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=100) - **-cov** \[0,100\] minimum coverage with master sequence (%) (def=0) - **-qid** \[0,100\] minimum sequence identity with master sequence (%) (def=0) - **-qsc** \[0,100\] minimum score per column with master sequence (default=-20.0) - **-mark** do not filter out sequences marked by "\>@"in their name line ### HMM-HMM alignment options: - **-norealign** do NOT realign displayed hits with MAC algorithm (def=realign) - **-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) - **-realign** realign displayed hits with max. accuracy (MAC) algorithm - **-excl** \ exclude query positions from the alignment, e.g. '1-33,97-168' - **-template\_excl** \ exclude template positions from the alignment, e.g. '1-33,97-168' - **-ovlp** \ banded alignment: forbid \ largest diagonals \|i-j\| of DP matrix (def=0) - **-alt** \ show up to this many alternative alignments with raw score \> smin(def=1) - **-smin** \ minimum raw score for alternative alignments (def=20.0) - **-shift** \[-1,1\] profile-profile score offset (def=-0.03) - **-corr** \[0,1\] weight of term for pair correlations (def=0.10) - **-sc** \ amino acid score (tja: template HMM at column j) (def=1) - 0 \= log2 Sum(tja\*qia/pa) (pa: aa background frequencies) - 1 \= log2 Sum(tja\*qia/pqa) (pqa = 1/2\*(pa+ta) ) - 2 \= 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} secondary structure scoring \[default=2\] - 0: \= no ss scoring - 1,2: \= ss scoring after or during alignment - 3,4: \= ss scoring after or during alignment, predicted vs. predicted - **-ssw** \[0,1\] weight of ss score (def=0.11) - **-ssa** \[0,1\] ss confusion matrix = (1-ssa)\*I + ssa\*psipred-confusion-matrix \[def=1.00) - **-wg** use global sequence weighting for realignment! ### Gap cost options: - **-gapb** \[0,inf\[ Transition pseudocount admixture (def=1.00) - **-gapd** \[0,inf\[ Transition pseudocount admixture for open gap (default=0.15) - **-gapd** \[0,inf\[ Transition pseudocount admixture for open gap (default=0.15) - **-gape** \[0,1.5\] Transition pseudocount admixture for extend gap (def=1.00) - **-gapf** \]0,inf\] factor to increase/reduce the gap open penalty for deletes (def=0.60) - **-gapg** \]0,inf\] factor to increase/reduce the gap open penalty for inserts (def=0.60) - **-gaph** \]0,inf\] factor to increase/reduce the gap extend penalty for deletes(def=0.60) - **-gapi** \]0,inf\] factor to increase/reduce the gap extend penalty for inserts(def=0.60) - **-egq** \[0,inf\[ penalty (bits) for end gaps aligned to query residues (def=0.00) - **-egt** \[0,inf\[ penalty (bits) for end gaps aligned to template residues (def=0.00) ### Pseudocount (pc) options: - Context specific hhm pseudocounts: - **-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) - **-pc\_hhm\_contxt\_a** \[0,1\] overall pseudocount admixture (def=0.9) - **-pc\_hhm\_contxt\_b** \[1,inf\[ Neff threshold value for mode 2 (def=4.0) - **-pc\_hhm\_contxt\_c** \[0,3\] extinction exponent c for mode 2 (def=1.0) - 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) - **-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) - **-pc\_hhm\_nocontxt\_c** \[0,3\] extinction exponent c for mode 2 (def=1.0) - Context-specific pseudo-counts: - **-nocontxt** use substitution-matrix instead of context-specific pseudocounts **-contxt** \ context file for computing context-specific pseudocounts (default=) - **-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** \ verbose mode: 0:no screen output 1:only warings 2: verbose (def=2) - **-atab** \ write all alignments in tabular layout to file - **-maxseq** \ max number of input rows (def=65535) - **-maxres** \ max number of HMM columns (def=20001) **-maxmem** \[1,inf\[ limit memory for realignment (in GB) (def=3.0) Example: hhalign **-i** T0187.a3m **-t** d1hz4a\_.hhm **-o** result.hhr