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This list of sequence alignment software is a compilation of software tools and web portals used in pairwise sequence alignment and multiple sequence alignment. See structural alignment software for structural alignment of proteins.


Database search only

Name Description Sequence Type* Link Authors Year

Name Description Sequence Type* Link Authors Year
BLAST local search with fast k-tuple heuristic (Basic Local Alignment Search Tool) Both NCBI EBI DDBJ DDBJ (psi-blast) GenomeNet PIR (protein only) Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ[1] 1990
CS-BLAST sequence-context specific BLAST, more sensitive than BLAST, FASTA, and SSEARCH. Position-specific iterative version CSI-BLAST more sensitive than PSI-BLAST Protein CS-BLAST server download Biegert A, Söding J[2] 2009
FASTA local search with fast k-tuple heuristic, slower but more sensitive than BLAST Both EBI DDBJ GenomeNet PIR (protein only)
GGSEARCH / GLSEARCH Global:Global (GG), Global:Local (GL) alignment with statistics Protein FASTA server
HMMER local and global search with profile Hidden Markov models, more sensitive than PSI-BLAST Both download Durbin R, Eddy SR, Krogh A, Mitchison G[3] 1998
HHpred / HHsearch pairwise comparison of profile Hidden Markov models; very sensitive, but can only search alignment databases (Pfam, PDB, InterPro...) Protein server download Söding J[4] 2005
IDF Inverse Document Frequency Both download
Infernal profile SCFG search RNA download Eddy S
PSI-BLAST position-specific iterative BLAST, local search with position-specific scoring matrices, much more sensitive than BLAST Protein NCBI PSI-BLAST Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ[5] 1997
SAM local and global search with profile Hidden Markov models, more sensitive than PSI-BLAST Both SAM Karplus K, Krogh A[6] 1999
SSEARCH Smith-Waterman search, slower but more sensitive than FASTA Both EBI DDBJ
*Sequence Type: Protein or nucleotide

Pairwise alignment

Name Description Sequence Type* Alignment Type** Link Author Year
Bioconductor Biostrings::pairwiseAlignment Dynamic programming Both Both + Ends-free site P. Aboyoun 2008
BioPerl dpAlign Dynamic programming Both Both + Ends-free site Y. M. Chan 2003
BLASTZ,LASTZ Seeded pattern-matching Nucleotide Local download,download Schwartz et al. 2004,2009
DNADot Web-based dot-plot tool Nucleotide Global server R. Bowen 1998
DOTLET Java-based dot-plot tool Both Global applet M. Pagni and T. Junier 1998
GGSEARCH, GLSEARCH Global:Global (GG), Global:Local (GL) alignment with statistics Protein Global in query FASTA server W. Pearson 2007
JAligner Open source Java implementation of Smith-Waterman Both Local JWS A. Moustafa 2005
LALIGN Multiple, non-overlapping, local similarity (same algorithm as SIM) Both Local non-overlapping server FASTA server W. Pearson 1991 (algorithm)
mAlign modelling alignment; models the information content of the sequences Nucleotide Both [1] [2] D. Powell, L. Allison and T. I. Dix 2004
matcher Memory-optimized Needleman-Wunsch dynamic programming (based on LALIGN) Both Local Pasteur I. Longden (modified from W. Pearson) 1999
MCALIGN2 explicit models of indel evolution DNA Global server J. Wang et al. 2006
MUMmer suffix tree based Nucleotide Global download S. Kurtz et al. 2004
needle Needleman-Wunsch dynamic programming Both SemiGlobal EBIPasteur A. Bleasby 1999
Ngila logarithmic and affine gap costs and explicit models of indel evolution Both Global download R. Cartwright 2007
Path Smith-Waterman on protein back-translation graph (detects frameshifts at protein level) Protein Local server download M. Gîrdea et al. 2009
PatternHunter Seeded pattern-matching Nucleotide Local download B. Ma et al. 2002–2004
ProbA (also propA) Stochastic partition function sampling via dynamic programming Both Global download U. Mückstein 2002
PyMOL "align" command aligns sequence & applies it to structure Protein Global (by selection) site W. L. DeLano 2007
REPuter suffix tree based Nucleotide Local download S. Kurtz et al. 2001
SABERTOOTH Alignment using predicted Connectivity Profiles Protein Global download on request F. Teichert, J. Minning, U. Bastolla, and M. Porto 2009
SEQALN Various dynamic programming Both Local or Global server M.S. Waterman and P. Hardy 1996
SIM, GAP, NAP, LAP Local similarity with varying gap treatments Both Local or global server X. Huang and W. Miller 1990-6
SIM Local similarity Both Local servers X. Huang and W. Miller 1991
SLIM Search Ultra-fast blocked alignment Both Both site S. Inglis, J. Cleary, S. Irvine, L. Trigg, L. Bloksberg et al. 2004
SSEARCH Local (Smith-Waterman) alignment with statistics Protein Local EBI FASTA server W. Pearson 1981 (Algorithm)
Sequences Studio Java applet demonstrating various algorithms from [7] Generic sequence Local and global code applet A.Meskauskas 1997 (reference book)
SWIFT suit Fast Local Alignment Searching DNA Local site K. Rasmussen, W. Gerlach 2005,2008
stretcher Memory-optimized but slow dynamic programming Both Global Pasteur I. Longden (modified from G. Myers and W. Miller) 1999
tranalign Aligns nucleic acid sequences given a protein alignment Nucleotide NA Pasteur G. Williams (modified from B. Pearson) 2002
water Smith-Waterman dynamic programming Both Local EBIPasteur A. Bleasby 1999
wordmatch k-tuple pairwise match Both NA Pasteur I. Longden 1998
YASS Seeded pattern-matching Nucleotide Local server download L. Noe and G. Kucherov 2003–2007
*Sequence Type: Protein or nucleotide. **Alignment Type: Local or global

Multiple sequence alignment

Name Description Sequence Type* Alignment Type** Link Author Year
ABA A-Bruijn alignment Protein Global download B.Raphaelet al. 2004
ALE manual alignment ; some software assistance Nucleotides Local download J. Blandy and K. Fogel 1994 (latest version 2007)
AMAP Sequence annealing Both Global server A. Schwartz and L. Pachter 2006
anon. fast, optimal alignment of three sequences using linear gap costs Nucleotides Global paper software D. Powell, L. Allison and T. I. Dix 2000
BAli-Phy Tree+Multi alignment ; Probabilistic/Bayesian ; Joint Estimation Both Global WWW+download BD Redelings and MA Suchard 2005 (latest version 2010)
CHAOS/DIALIGN Iterative alignment Both Local (preferred) server M. Brudno and B. Morgenstern 2003
ClustalW Progressive alignment Both Local or Global download EBI DDBJ PBIL EMBNet GenomeNet Thompson et al. 1994
CodonCode Aligner Multi alignment; ClustalW & Phrap support Nucleotides Local or Global download P. Richterich et al. 2003 (latest version 2009)
DIALIGN-TX and DIALIGN-T Segment-based method Both Local (preferred) or Global download and server A.R.Subramanian 2005 (latest version 2008)
DNA Alignment Segment-based method for intraspecific alignments Both Local (preferred) or Global server A.Roehl 2005 (latest version 2008)
FSA Sequence annealing Both Global download and server R. K. Bradley et al. 2008
Geneious Progressive/Iterative alignment; ClustalW plugin Both Local or Global download A.J. Drummond et al. 2005 (latest version 2009)
Kalign Progressive alignment Both Global serverEBI MPItoolkit T. Lassmann 2005
MAFFT Progressive/iterative alignment Both Local or Global GenomeNet MAFFT K. Katoh et al. 2005
MARNA Multiple Alignment of RNAs RNA Local server download S. Siebert et al. 2005
MAVID Progressive alignment Both Global server N. Bray and L. Pachter 2004
MSA Dynamic programming Both Local or Global download D.J. Lipman et al. 1989 (modified 1995)
MSAProbs Dynamic programming Protein Global download Y. Liu, B. Schmidt, D. Maskell 2010
MULTALIN Dynamic programming/clustering Both Local or Global server F. Corpet 1988
Multi-LAGAN Progressive dynamic programming alignment Both Global server M. Brudno et al. 2003
MUSCLE Progressive/iterative alignment Both Local or Global server R. Edgar 2004
Opal Progressive/iterative alignment Both Local or Global download T. Wheeler and J. Kececioglu 2007
Pecan Probabilistic/consistency DNA Global download B. Paten et al. 2008
POA Partial order/hidden Markov model Protein Local or Global download C. Lee 2002
Probalign Probabilistic/consistency with partition function probabilities Protein Global server Roshan and Livesay 2006
ProbCons Probabilistic/consistency Protein Local or Global server C. Do et al. 2005
PROMALS3D Progressive alignment/hidden Markov model/Secondary structure/3D structure Protein Global server J. Pei et al. 2008
PRRN/PRRP Iterative alignment (especially refinement) Protein Local or Global PRRP PRRN Y. Totoki (based on O. Gotoh) 1991 and later
PSAlign Alignment preserving non-heuristic Both Local or Global download S.H. Sze, Y. Lu, Q. Yang. 2006
RevTrans Combines DNA and Protein alignment, by back translating the protein alignment to DNA. DNA/Protein (special) Local or Global server Wernersson and Pedersen 2003 (newest version 2005)
SAGA Sequence alignment by genetic algorithm Protein Local or Global download C. Notredame et al. 1996 (new version 1998)
SAM Hidden Markov model Protein Local or Global server A. Krogh et al. 1994 (most recent version 2002)
StatAlign Bayesian co-estimation of alignment and phylogeny (MCMC) Both Global download A. Novak et al. 2008
Stemloc Multiple alignment and secondary structure prediction RNA Local or Global download I. Holmes 2005
T-Coffee More sensitive progressive alignment Both Local or Global server download C. Notredame et al. 2000 (newest version 2008)
UGENE Supports multiple alignment with MUSCLE and KAlign plugins, local sequences alignment with Smith-Waterman algorithm. Both Local or Global download UGENE team 2009
*Sequence Type: Protein or nucleotide. **Alignment Type: Local or global

Genomics analysis

Name Description Sequence Type* Link
SLAM Gene finding, alignment, annotation (human-mouse homology identification) Nucleotide server
Mauve Multiple alignment of rearranged genomes Nucleotide download
MGA Multiple Genome Aligner Nucleotide download
Mulan Local multiple alignments of genome-length sequences Nucleotide server
Multiz Multiple alignment of genomes Nucleotide download
PLAST-ncRNA Search for ncRNAs in genomes by partition function local alignment Nucleotide server
Sequerome Profiling sequence alignment data with major servers/services Nucleotide/peptide server
AVID Pairwise global alignment with whole genomes Nucleotide server
SIBsim4 / Sim4 A program designed to align an expressed DNA sequence with a genomic sequence, allowing for introns Nucleotide download
Shuffle-LAGAN Pairwise glocal alignment of completed genome regions Nucleotide server
ACT (Artemis Comparison Tool) Synteny and comparative genomics Nucleotide server
*Sequence Type: Protein or nucleotide

Motif finding

Name Description Sequence Type* Link
MEME/MAST Motif discovery and search Both server
BLOCKS Ungapped motif identification from BLOCKS database Both server
eMOTIF Extraction and identification of shorter motifs Both servers
Gibbs motif sampler Stochastic motif extraction by statistical likelihood Both server (one of many implementations)
HMMTOP Prediction of transmembrane helices and topology of proteins Protein homepage & download
JCoils Prediction of Coiled coil and Leucine Zipper Protein homepage & download
TEIRESIAS Motif extraction and database search Both server
PRATT Pattern generation for use with ScanProsite Protein server
ScanProsite Motif database search tool Protein server
PHI-Blast Motif search and alignment tool Both Pasteur
I-sites Local structure motif library Protein server
*Sequence Type: Protein or nucleotide

Benchmarking

Name Link Authors
BAliBASE download Thompson, Plewniak, Poch
HOMSTRAD download Stebbings, Mizuguchi
Oxbench download Raghava, Searle, Audley, Barber, Barton
PFAM download
PREFAB download Edgar
SABmark download Van Walle, Lasters, Wyns
SMART download Letunic, Copley, Schmidt, Ciccarelli, Doerks, Schultz, Ponting, Bork

Alignment Viewers/Editors
Please see the List of alignment visualization software.

Short-Read Sequence Alignment

Name Description Multi-threaded License Link
BFAST Explicit time and accuracy tradeoff with a prior accuracy estimation, supported by indexing the reference sequences. Optimally compresses indexes. Can handle billions of short reads. Can handle insertions, deletions, SNPs, and color errors (can map ABI SOLiD color space reads). Performs a full Smith Waterman alignment. Yes (POSIX) GPL link
BLASTN BLAST's nucleotide alignment program, slow and not accurate for short reads, and uses a sequence database (EST, sanger sequence) rather than a reference genome. link
BLAT Made by Jim Kent. Can handle one mismatch in initial alignment step. Yes (client/server). Free for academic and non-commercial use. link
Bowtie Uses a Burrows-Wheeler to create a permanent, reusable index of the genome; 1.3 GB memory footprint for human genome. Aligns more than 25 million Illumina reads in 1 CPU hour. Supports Maq-like and SOAP-like alignment policies. Yes (POSIX) Artistic License link
CASHX Quantify and manage large quantities of short-read sequence data. CASHX pipeline contains a set of tools that can be used together or as independent modules on their own. This algorithm is very accurate for perfect hits to a reference genome. No Free for academic and non-commercial use. link
CUDA-EC Short-read alignment error correction using GPUs. Yes (GPU enabled) CUDA-EC-
ELAND Implemented by Illumina. Includes ungapped alignment with a finite read length.
GMAP and GSNAP Robust, fast, short-read alignment. GMAP: singleton reads; GSNAP: paired reads. Useful for digital gene expression, SNP and indel genotyping. Developed by Tom Wu at Genentech. Implemented by NCGR in Alpheus. Yes Free for academic and non-commercial use. [3]
LAST link
MAQ Ungapped alignment that takes into account quality scores for each base. GPL link
MOM MOM or maximum oligonucleotide mapping is a query matching tool that captures a maximal length match within the short read. Yes [4]
MOSAIK Fast gapped aligner and reference-guided assembler. Aligns reads using a banded Smith-Waterman algorithm seeded by results from a k-mer hashing scheme. Supports reads ranging in size from very short to very long. Yes link
Novoalign Gapped alignment of single end and paired end Illumina GA I & II reads and reads from the new Helicos Heliscope Genome Analyzer. High sensitivity and specificity, using base qualities at all steps in the alignment. Includes adapter trimming, base quality calibration, Bi-Seq alignment, and option to report multiple alignments per read. Multi-threading and MPI versions available with paid license. Single threaded version free for academic and non-commercial use. Novocraft
PALMapper PALMapper, efficiently computes both spliced and unspliced alignments at high accuracy. Relying on a machine learning strategy combined with a fast mapping based on a banded Smith-Waterman-like algorithm it aligns around 7 million reads per hour on a single CPU. It refines the originally proposed QPALMA approach. Yes GPL [5]
PerM Indexes the genome with periodic seeds to quickly find alignments with full sensitivity up to four mismatches. It can map Illumina and SOLiD reads. Unlike most mapping programs, speed increases for longer read lengths. Yes GPL link
QPalma Is able to take advantage of quality scores, intron lengths and computation splice site predictions to perform and performs an unbiased alignment. Can be trained to the specifics of a RNA-seq experiment and genome. Useful for splice site/intron discovery and for gene model building. (See PALMapper for a faster version). Yes (client/server) GPLv2 link
RazerS No read length limit. Hamming or edit distance mapping with configurable error rates. Configurable and predictable sensitivity (runtime/sensitivity tradeoff). Supports paired-end read mapping. LGPL link
RMAP Read lengths can range from 20bp to at most 64bp. Uses the "exclusion principle" to allow for mismatches and look-up reads in an index. link
SeqMap Up to 5 mixed substitutions and insertions/deletions. Various tuning options and input/output formats. Free for academic and non-commercial use. link
Shrec Short read error correction with a Suffix trie data structure. Yes (Java) link
SHRiMP Indexes the reads instead of the reference genome. Uses masks to generate possible keys. Can map ABI SOLiD color space reads. BSD derivative link
SLIDER Slider is an application for the Illumina Sequence Analyzer output that uses the "probability" files instead of the sequence files as an input for alignment to a reference sequence or a set of reference sequences. link
SLIM Search Extremely fast, tolerant to high indel and substitution counts. Includes full read alignment. Yes Commercial/High-use customers can join beta programme (Q2 '09) link
SOAP Robust with a small (1-3) number of gaps and mismatches. Speed improvement over BLAT, uses a 12 letter hash table.Now SOAP2 is much faster than the first version. YES(MULTITHREAD) GPL; SOAP2 source is currently unavailable link
SOCS For ABI SOLiD technologies. Significant increase in time to map reads with mismatches (or color errors). Uses an iterative version of the Rabin-Karp string search algorithm. Yes link
SSAHA and SSAHA2 Fast for a small number of variants. Free for academic and non-commercial use. link
Taipan de-novo Assembler for Illumina reads Free for academic and non-commercial use. link
ZOOM 100% sensitivity for a reads between 15 - 240bp with practical mismatches. Very fast. Support insertions and deletions. Works with Illumina & SOLiD instruments, not 454. Yes (GUI) No (CLI). Commercial link

See also
* List of open source bioinformatics software

References
1. ^ Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (October 1990). "Basic local alignment search tool". Journal of Molecular Biology 215 (3): 403–10. doi:10.1006/jmbi.1990.9999. PMID 2231712.
2. ^ Biegert A, Söding J (March 2009). "Sequence context-specific profiles for homology searching". Proceedings of the National Academy of Sciences of the United States of America 106 (10): 3770–5. doi:10.1073/pnas.0810767106. PMID 19234132.
3. ^ Durbin, Richard; Eddy, Sean R.; Krogh, Anders et al., eds (1998). Biological sequence analysis: probalistic models of proteins and nucleic acids. Cambridge, UK: Cambridge University Press. ISBN 978-0-521-62971-3. [page needed]
4. ^ Söding J (April 2005). "Protein homology detection by HMM-HMM comparison". Bioinformatics 21 (7): 951–60. doi:10.1093/bioinformatics/bti125. PMID 15531603.
5. ^ Altschul SF, Madden TL, Schäffer AA, et al. (September 1997). "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs". Nucleic Acids Research 25 (17): 3389–402. doi:10.1093/nar/25.17.3389. PMID 9254694.
6. ^ Hughey, R, Karplus, K., and Krogh, A. (1999) SAM: sequence alignment and modeling software system. Technical report UCSC-CRL 99-11. University of California, Santa Cruz, CA.
7. ^ Dan Gusfield (1997). Algorithms on strings, trees and sequences. Cambridge university press, ISBN 0-521-58519-8.

External links
* Pollard et al. (2004) (PubMed Central free fulltext): The authors discuss LAGAN, CHAOS, and Dialign as the most effective tools tested for certain uses.

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