List of sequence alignment software

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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[edit]

Name Description Sequence type* Authors Year
BLAST Local search with fast k-tuple heuristic (Basic Local Alignment Search Tool) Both Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ[1] 1990
HPC-BLAST NCBI compliant multinode and multicore BLAST wrapper. Distributed with the latest version of BLAST, this wrapper facilitates parallelization of the algorithm on modern hybrid architectures with many nodes and many cores within each node.[2] Protein Burdyshaw CE, Sawyer S, Horton MD, Brook RG, Rekapalli B 2017
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 Angermueller C, Biegert A, Soeding J[3] 2013
CUDASW++ GPU accelerated Smith Waterman algorithm for multiple shared-host GPUs Protein Liu Y, Maskell DL and Schmidt B 2009/2010
DIAMOND BLASTX and BLASTP aligner based on double indexing Protein Buchfink B, Xie C, Huson DH, Reuter K, Drost HG [4][5] 2015/2021
FASTA Local search with fast k-tuple heuristic, slower but more sensitive than BLAST Both
GGSEARCH, GLSEARCH Global:Global (GG), Global:Local (GL) alignment with statistics Protein
Genome Magician Software for ultra fast local DNA sequence motif search and pairwise alignment for NGS data (FASTA, FASTQ). DNA Hepperle D ( 2020
Genoogle Genoogle uses indexing and parallel processing techniques for searching DNA and Proteins sequences. It is developed in Java and open source. Both Albrecht F 2015
HMMER Local and global search with profile Hidden Markov models, more sensitive than PSI-BLAST Both Durbin R, Eddy SR, Krogh A, Mitchison G[6] 1998
HH-suite Pairwise comparison of profile Hidden Markov models; very sensitive Protein Söding J[7][8] 2005/2012
IDF Inverse Document Frequency Both
Infernal Profile SCFG search RNA Eddy S
KLAST High-performance general purpose sequence similarity search tool Both 2009/2014
LAMBDA High performance local aligner compatible to BLAST, but much faster; supports SAM/BAM Protein Hannes Hauswedell, Jochen Singer, Knut Reinert[9] 2014
MMseqs2 Software suite to search and cluster huge sequence sets. Similar sensitivity to BLAST and PSI-BLAST but orders of magnitude faster Protein Steinegger M, Mirdita M, Galiez C, Söding J[10] 2017
USEARCH Ultra-fast sequence analysis tool Both Edgar, R. C. (2010). "Search and clustering orders of magnitude faster than BLAST". Bioinformatics. 26 (19): 2460–2461. doi:10.1093/bioinformatics/btq461. PMID 20709691. publication 2010
OSWALD OpenCL Smith-Waterman on Altera's FPGA for Large Protein Databases Protein Rucci E, García C, Botella G, De Giusti A, Naiouf M, Prieto-Matías M[11] 2016
parasail Fast Smith-Waterman search using SIMD parallelization Both Daily J 2015
PSI-BLAST Position-specific iterative BLAST, local search with position-specific scoring matrices, much more sensitive than BLAST Protein Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ[12] 1997
PSI-Search Combining the Smith-Waterman search algorithm with the PSI-BLAST profile construction strategy to find distantly related protein sequences, and preventing homologous over-extension errors. Protein Li W, McWilliam H, Goujon M, Cowley A, Lopez R, Pearson WR[13] 2012
R&R Retrieve and Relate (R&R) is a high performance yet sensitive multi-database search engine, capable of searching in parallel through DNA,RNA and Protein sequences. Both 2019
ScalaBLAST Highly parallel Scalable BLAST Both Oehmen et al.[14] 2011
Sequilab Linking and profiling sequence alignment data from NCBI-BLAST results with major sequence analysis servers/services Nucleotide, peptide 2010
SAM Local and global search with profile Hidden Markov models, more sensitive than PSI-BLAST Both Karplus K, Krogh A[15] 1999
SSEARCH Smith-Waterman search, slower but more sensitive than FASTA Both
SWAPHI First parallelized algorithm employing the emerging Intel Xeon Phis to accelerate Smith-Waterman protein database search Protein Liu Y and Schmidt B 2014
SWAPHI-LS First parallel Smith-Waterman algorithm exploiting Intel Xeon Phi clusters to accelerate the alignment of long DNA sequences DNA Liu Y, Tran TT, Lauenroth F, Schmidt B 2014
SWIMM Smith-Waterman implementation for Intel Multicore and Manycore architectures Protein Rucci E, García C, Botella G, De Giusti A, Naiouf M and Prieto-Matías M[16] 2015
SWIMM2.0 Enhanced Smith-Waterman on Intel's Multicore and Manycore architectures based on AVX-512 vector extensions Protein Rucci E, García C, Botella G, De Giusti A, Naiouf M and Prieto-Matías M[17] 2018
SWIPE Fast Smith-Waterman search using SIMD parallelization Both Rognes T 2011

*Sequence type: protein or nucleotide

Pairwise alignment[edit]

Name Description Sequence type* Alignment type** Author Year
ACANA Fast heuristic anchor based pairwise alignment Both Both Huang, Umbach, Li 2005
AlignMe Alignments for membrane protein sequences Protein Both M. Stamm, K. Khafizov, R. Staritzbichler, L.R. Forrest 2013
ALLALIGN For DNA, RNA and protein molecules up to 32MB, aligns all sequences of size K or greater. Similar alignments are grouped together for analysis. Automatic repetitive sequence filter. Both Local E. Wachtel 2017
Bioconductor Biostrings::pairwiseAlignment Dynamic programming Both Both + Ends-free P. Aboyoun 2008
BioPerl dpAlign Dynamic programming Both Both + Ends-free Y. M. Chan 2003
BLASTZ, LASTZ Seeded pattern-matching Nucleotide Local Schwartz et al.[18][19] 2004,2009
CUDAlign DNA sequence alignment of unrestricted size in single or multiple GPUs Nucleotide Local, SemiGlobal, Global E. Sandes[20][21][22] 2011-2015
DNADot Web-based dot-plot tool Nucleotide Global R. Bowen 1998
DOTLET Java-based dot-plot tool Both Global M. Pagni and T. Junier 1998
FEAST Posterior based local extension with descriptive evolution model Nucleotide Local A. K. Hudek and D. G. Brown 2010
Genome Compiler Genome Compiler Align chromatogram files (.ab1, .scf) against a template sequence, locate errors, and correct them instantly. Nucleotide Local Genome Compiler Corporation 2014
G-PAS GPU-based dynamic programming with backtracking Both Local, SemiGlobal, Global W. Frohmberg, M. Kierzynka et al. 2011
GapMis Does pairwise sequence alignment with one gap Both SemiGlobal K. Frousios, T. Flouri, C. S. Iliopoulos, K. Park, S. P. Pissis, G. Tischler 2012
Genome Magician Software for ultra fast local DNA sequence motif search and pairwise alignment for NGS data (FASTA, FASTQ). DNA Local, SemiGlobal, Global Hepperle D ( 2020
GGSEARCH, GLSEARCH Global:Global (GG), Global:Local (GL) alignment with statistics Protein Global in query W. Pearson 2007
JAligner Java open-source implementation of Smith-Waterman Both Local A. Moustafa 2005
K*Sync Protein sequence to structure alignment that includes secondary structure, structural conservation, structure-derived sequence profiles, and consensus alignment scores Protein Both D. Chivian & D. Baker[23] 2003
LALIGN Multiple, non-overlapping, local similarity (same algorithm as SIM) Both Local non-overlapping W. Pearson 1991 (algorithm)
NW-align Standard Needleman-Wunsch dynamic programming algorithm Protein Global Y Zhang 2012
mAlign modelling alignment; models the information content of the sequences Nucleotide Both D. Powell, L. Allison and T. I. Dix 2004
matcher Waterman-Eggert local alignment (based on LALIGN) Both Local I. Longden (modified from W. Pearson) 1999
MCALIGN2 explicit models of indel evolution DNA Global J. Wang et al. 2006
MegAlign Pro (Lasergene Molecular Biology) Software to align DNA, RNA, protein, or DNA + protein sequences via pairwise and multiple sequence alignment algorithms including MUSCLE, Mauve, MAFFT, Clustal Omega, Jotun Hein, Wilbur-Lipman, Martinez Needleman-Wunsch, Lipman-Pearson and Dotplot analysis. Both Both DNASTAR 1993-2016
MUMmer suffix tree based Nucleotide Global S. Kurtz et al. 2004
needle Needleman-Wunsch dynamic programming Both SemiGlobal A. Bleasby 1999
Ngila logarithmic and affine gap costs and explicit models of indel evolution Both Global R. Cartwright 2007
NW Needleman-Wunsch dynamic programming Both Global A.C.R. Martin 1990-2015
parasail C/C++/Python/Java SIMD dynamic programming library for SSE, AVX2 Both Global, Ends-free, Local J. Daily 2015
Path Smith-Waterman on protein back-translation graph (detects frameshifts at protein level) Protein Local M. Gîrdea et al.[24] 2009
PatternHunter Seeded pattern-matching Nucleotide Local B. Ma et al.[25][26] 2002–2004
ProbA (also propA) Stochastic partition function sampling via dynamic programming Both Global U. Mückstein 2002
PyMOL "align" command aligns sequence & applies it to structure Protein Global (by selection) W. L. DeLano 2007
REPuter suffix tree based Nucleotide Local S. Kurtz et al. 2001
SABERTOOTH Alignment using predicted Connectivity Profiles Protein Global F. Teichert, J. Minning, U. Bastolla, and M. Porto 2009
Satsuma Parallel whole-genome synteny alignments DNA Local M.G. Grabherr et al. 2010
SEQALN Various dynamic programming Both Local or global M.S. Waterman and P. Hardy 1996
SIM, GAP, NAP, LAP Local similarity with varying gap treatments Both Local or global X. Huang and W. Miller 1990-6
SIM Local similarity Both Local X. Huang and W. Miller 1991
SPA: Super pairwise alignment Fast pairwise global alignment Nucleotide Global Shen, Yang, Yao, Hwang 2002
SSEARCH Local (Smith-Waterman) alignment with statistics Protein Local W. Pearson 1981 (Algorithm)
Sequences Studio Java applet demonstrating various algorithms from[27] Generic sequence Local and global A.Meskauskas 1997 (reference book)
SWIFOLD Smith-Waterman Acceleration on Intel's FPGA with OpenCL for Long DNA Sequences Nucleotide Local E. Rucci[28][29] 2017-2018
SWIFT suit Fast Local Alignment Searching DNA Local K. Rasmussen,[30] W. Gerlach 2005,2008
stretcher Memory-optimized Needleman-Wunsch dynamic programming Both Global I. Longden (modified from G. Myers and W. Miller) 1999
tranalign Aligns nucleic acid sequences given a protein alignment Nucleotide NA G. Williams (modified from B. Pearson) 2002
UGENE Opensource Smith-Waterman for SSE/CUDA, Suffix array based repeats finder & dotplot Both Both UniPro 2010
water Smith-Waterman dynamic programming Both Local A. Bleasby 1999
wordmatch k-tuple pairwise match Both NA I. Longden 1998
YASS Seeded pattern-matching Nucleotide Local L. Noe and G. Kucherov[31] 2004

*Sequence type: protein or nucleotide **Alignment type: local or global

Multiple sequence alignment[edit]

Name Description Sequence type* Alignment type** Author Year License
ABA A-Bruijn alignment Protein Global B.Raphael et al. 2004 Proprietary, freeware for education, research, nonprofit
ALE manual alignment ; some software assistance Nucleotides Local J. Blandy and K. Fogel 1994 (latest version 2007) Free, GPL2
ALLALIGN For DNA, RNA and protein molecules up to 32MB, aligns all sequences of size K or greater, MSA or within a single molecule. Similar alignments are grouped together for analysis. Automatic repetitive sequence filter. Both Local E. Wachtel 2017 Free
AMAP Sequence annealing Both Global A. Schwartz and L. Pachter 2006
anon. fast, optimal alignment of three sequences using linear gap costs Nucleotides Global D. Powell, L. Allison and T. I. Dix 2000
BAli-Phy Tree+multi-alignment; probabilistic-Bayesian; joint estimation Both + Codons Global BD Redelings and MA Suchard 2005 (latest version 2018) Free, GPL
Base-By-Base Java-based multiple sequence alignment editor with integrated analysis tools Both Local or global R. Brodie et al. 2004 Proprietary, freeware, must register
CHAOS, DIALIGN Iterative alignment Both Local (preferred) M. Brudno and B. Morgenstern 2003
ClustalW Progressive alignment Both Local or global Thompson et al. 1994 Free, LGPL
CodonCode Aligner Multi-alignment; ClustalW & Phrap support Nucleotides Local or global P. Richterich et al. 2003 (latest version 2009)
Compass COmparison of Multiple Protein sequence Alignments with assessment of Statistical Significance Protein Global R.I. Sadreyev, et al. 2009
DECIPHER Progressive-iterative alignment Both Global Erik S. Wright 2014 Free, GPL
DIALIGN-TX and DIALIGN-T Segment-based method Both Local (preferred) or Global A.R.Subramanian 2005 (latest version 2008)
DNA Alignment Segment-based method for intraspecific alignments Both Local (preferred) or Global A.Roehl 2005 (latest version 2008)
DNA Baser Sequence Assembler Multi-alignment; Full automatic sequence alignment; Automatic ambiguity correction; Internal base caller; Command line seq alignment Nucleotides Local or global Heracle BioSoft SRL 2006 (latest version 2018) Commercial (some modules are freeware)
DNADynamo linked DNA to Protein multiple alignment with MUSCLE, Clustal and Smith-Waterman Both Local or global DNADynamo 2004 (newest version 2017)
EDNA Energy Based Multiple Sequence Alignment for DNA Binding Sites Nucleotides Local or global Salama, RA. et al. 2013
FAMSA Progressive alignment for extremely large protein families (hundreds of thousands of members) Protein Global Deorowicz et al. 2016 Free, GPL 3
FSA Sequence annealing Both Global R. K. Bradley et al. 2008
Geneious Progressive-Iterative alignment; ClustalW plugin Both Local or global A.J. Drummond et al. 2005 (latest version 2017)
GUIDANCE Quality control and filtering of multiple sequence alignments Both Local or global O. Penn et al. 2010 (latest version 2015)
Kalign Progressive alignment Both Global T. Lassmann 2005
MACSE Progressive-iterative alignment. Multiple alignment of coding sequences accounting for frameshifts and stop codons. Nucleotides Global V. Ranwez et al. 2011 (latest version, v2.07 2023)
MAFFT Progressive-iterative alignment Both Local or global K. Katoh et al. 2005 Free, BSD
MARNA Multi-alignment of RNAs RNA Local S. Siebert et al. 2005
MAVID Progressive alignment Both Global N. Bray and L. Pachter 2004
MegAlign Pro (Lasergene Molecular Biology) Software to align DNA, RNA, protein, or DNA + protein sequences via pairwise and multiple sequence alignment algorithms including MUSCLE, Mauve, MAFFT, Clustal Omega, Jotun Hein, Wilbur-Lipman, Martinez Needleman-Wunsch, Lipman-Pearson and Dotplot analysis. Both Local or global DNASTAR 1993-2023
MSA Dynamic programming Both Local or global D.J. Lipman et al. 1989 (modified 1995)
MSAProbs Dynamic programming Protein Global Y. Liu, B. Schmidt, D. Maskell 2010
MULTALIN Dynamic programming-clustering Both Local or global F. Corpet 1988
Multi-LAGAN Progressive dynamic programming alignment Both Global M. Brudno et al. 2003
MUSCLE Progressive-iterative alignment Both Local or global R. Edgar 2004
Opal Progressive-iterative alignment Both Local or global T. Wheeler and J. Kececioglu 2007 (latest stable 2013, latest beta 2016)
Pecan Probabilistic-consistency DNA Global B. Paten et al. 2008
Phylo A human computing framework for comparative genomics to solve multiple alignment Nucleotides Local or global McGill Bioinformatics 2010
PMFastR Progressive structure aware alignment RNA Global D. DeBlasio, J Braund, S Zhang 2009
Praline Progressive-iterative-consistency-homology-extended alignment with preprofiling and secondary structure prediction Protein Global J. Heringa 1999 (latest version 2009)
PicXAA Nonprogressive, maximum expected accuracy alignment Both Global S.M.E. Sahraeian and B.J. Yoon 2010
POA Partial order/hidden Markov model Protein Local or global C. Lee 2002
Probalign Probabilistic/consistency with partition function probabilities Protein Global Roshan and Livesay 2006 Free, public domain
ProbCons Probabilistic/consistency Protein Local or global C. Do et al. 2005 Free, public domain
PROMALS3D Progressive alignment/hidden Markov model/Secondary structure/3D structure Protein Global J. Pei et al. 2008
PRRN/PRRP Iterative alignment (especially refinement) Protein Local or global Y. Totoki (based on O. Gotoh) 1991 and later
PSAlign Alignment preserving non-heuristic Both Local or global 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 Wernersson and Pedersen 2003 (newest version 2005)
SAGA Sequence alignment by genetic algorithm Protein Local or global C. Notredame et al. 1996 (new version 1998)
SAM Hidden Markov model Protein Local or global A. Krogh et al. 1994 (most recent version 2002)
Se-Al Manual alignment Both Local A. Rambaut 2002
StatAlign Bayesian co-estimation of alignment and phylogeny (MCMC) Both Global A. Novak et al. 2008
Stemloc Multiple alignment and secondary structure prediction RNA Local or global I. Holmes 2005 Free, GPL 3 (parte de DART)
T-Coffee More sensitive progressive alignment Both Local or global C. Notredame et al. 2000 (newest version 2008) Free, GPL 2
UGENE Supports multiple alignment with MUSCLE, KAlign, Clustal and MAFFT plugins Both Local or global UGENE team 2010 (newest version 2020) Free, GPL 2
VectorFriends VectorFriends Aligner, MUSCLE plugin, and ClustalW plugin Both Local or global BioFriends team 2013 Proprietary, freeware for academic use
GLProbs Adaptive pair-Hidden Markov Model based approach Protein Global Y. Ye et al. 2013

*Sequence type: protein or nucleotide. **Alignment type: local or global

Genomics analysis[edit]

Name Description Sequence type*
EAGLE [32] An ultra-fast tool to find relative absent words in genomic data Nucleotide
ACT (Artemis Comparison Tool) Synteny and comparative genomics Nucleotide
AVID Pairwise global alignment with whole genomes Nucleotide
BLAT Alignment of cDNA sequences to a genome. Nucleotide
DECIPHER Alignment of rearranged genomes using 6 frame translation Nucleotide
FLAK Fuzzy whole genome alignment and analysis Nucleotide
GMAP Alignment of cDNA sequences to a genome. Identifies splice site junctions with high accuracy. Nucleotide
Splign Alignment of cDNA sequences to a genome. Identifies splice site junctions with high accuracy. Able to recognize and separate gene duplications. Nucleotide
Mauve Multiple alignment of rearranged genomes Nucleotide
MGA Multiple Genome Aligner Nucleotide
Mulan Local multiple alignments of genome-length sequences Nucleotide
Multiz Multiple alignment of genomes Nucleotide
PLAST-ncRNA Search for ncRNAs in genomes by partition function local alignment Nucleotide
Sequerome Profiling sequence alignment data with major servers/services Nucleotide, peptide
Sequilab Profiling sequence alignment data from NCBI-BLAST results with major servers-services Nucleotide, peptide
Shuffle-LAGAN Pairwise global alignment of completed genome regions Nucleotide
SIBsim4, Sim4 A program designed to align an expressed DNA sequence with a genomic sequence, allowing for introns Nucleotide
SLAM Gene finding, alignment, annotation (human-mouse homology identification) Nucleotide
SRPRISM An efficient aligner for assemblies with explicit guarantees, aligning reads without splices Nucleotide

*Sequence type: protein or nucleotide

Motif finding[edit]

Name Description Sequence type*
PMS Motif search and discovery Both
FMM Motif search and discovery (can get also positive & negative sequences as input for enriched motif search) Nucleotide
BLOCKS Ungapped motif identification from BLOCKS database Both
eMOTIF Extraction and identification of shorter motifs Both
Gibbs motif sampler Stochastic motif extraction by statistical likelihood Both
HMMTOP Prediction of transmembrane helices and topology of proteins Protein
I-sites Local structure motif library Protein
JCoils Prediction of Coiled coil and Leucine Zipper Protein
MEME/MAST Motif discovery and search Both
CUDA-MEME GPU accelerated MEME (v4.4.0) algorithm for GPU clusters Both
MERCI Discriminative motif discovery and search Both
PHI-Blast Motif search and alignment tool Both
Phyloscan Motif search tool Nucleotide
PRATT Pattern generation for use with ScanProsite Protein
ScanProsite Motif database search tool Protein
TEIRESIAS Motif extraction and database search Both
BASALT Multiple motif and regular expression search Both

*Sequence type: protein or nucleotide


Name Authors
PFAM 30.0 (2016)
SMART (2015) Letunic, Copley, Schmidt, Ciccarelli, Doerks, Schultz, Ponting, Bork
BAliBASE 3 (2015) Thompson, Plewniak, Poch
Oxbench (2011) Raghava, Searle, Audley, Barber, Barton
Benchmark collection (2009) Edgar
HOMSTRAD (2005) Mizuguchi
PREFAB 4.0 (2005) Edgar
SABmark (2004) Van Walle, Lasters, Wyns

Alignment viewers, editors[edit]

Please see List of alignment visualization software.

Short-read sequence alignment[edit]

Name Description paired-end option Use FASTQ quality Gapped Multi-threaded License Reference Year
Arioc Computes Smith-Waterman gapped alignments and mapping qualities on one or more GPUs. Supports BS-seq alignments. Processes 100,000 to 500,000 reads per second (varies with data, hardware, and configured sensitivity). Yes No Yes Yes Free, BSD [33] 2015
BarraCUDA A GPGPU accelerated Burrows–Wheeler transform (FM-index) short read alignment program based on BWA, supports alignment of indels with gap openings and extensions. Yes No Yes Yes, POSIX Threads and CUDA Free, GPL
BBMap Uses a short kmers to rapidly index genome; no size or scaffold count limit. Higher sensitivity and specificity than Burrows–Wheeler aligners, with similar or greater speed. Performs affine-transform-optimized global alignment, which is slower but more accurate than Smith-Waterman. Handles Illumina, 454, PacBio, Sanger, and Ion Torrent data. Splice-aware; capable of processing long indels and RNA-seq. Pure Java; runs on any platform. Used by the Joint Genome Institute. Yes Yes Yes Yes Free, BSD 2010
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 Threads Free, GPL [34] 2009
BigBWA Runs the Burrows–Wheeler Aligner-BWA on a Hadoop cluster. It supports the algorithms BWA-MEM, BWA-ALN, and BWA-SW, working with paired and single reads. It implies an important reduction in the computational time when running in a Hadoop cluster, adding scalability and fault-tolerance. Yes Low quality bases trimming Yes Yes Free, GPL 3 [35] 2015
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.
BLAT Made by Jim Kent. Can handle one mismatch in initial alignment step. Yes, client-server Proprietary, freeware for academic and noncommercial use [36] 2002
Bowtie Uses a Burrows–Wheeler transform 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 Yes No Yes, POSIX Threads Free, Artistic [37] 2009
BWA Uses a Burrows–Wheeler transform to create an index of the genome. It's a bit slower than Bowtie but allows indels in alignment. Yes Low quality bases trimming Yes Yes Free, GPL [38] 2009
BWA-PSSM A probabilistic short read aligner based on the use of position specific scoring matrices (PSSM). The aligner is adaptable in the sense that it can take into account the quality scores of the reads and models of data specific biases, such as those observed in Ancient DNA, PAR-CLIP data or genomes with biased nucleotide compositions.[39] Yes Yes Yes Yes Free, GPL [39] 2014
CASHX Quantify and manage large quantities of short-read sequence data. CASHX pipeline contains a set of tools that can be used together, or separately as modules. This algorithm is very accurate for perfect hits to a reference genome. No Proprietary, freeware for academic and noncommercial use
Cloudburst Short-read mapping using Hadoop MapReduce Yes, Hadoop MapReduce Free, Artistic
CUDA-EC Short-read alignment error correction using GPUs. Yes, GPU enabled
CUSHAW A CUDA compatible short read aligner to large genomes based on Burrows–Wheeler transform Yes Yes No Yes (GPU enabled) Free, GPL [40] 2012
CUSHAW2 Gapped short-read and long-read alignment based on maximal exact match seeds. This aligner supports both base-space (e.g. from Illumina, 454, Ion Torrent and PacBio sequencers) and ABI SOLiD color-space read alignments. Yes No Yes Yes Free, GPL 2014
CUSHAW2-GPU GPU-accelerated CUSHAW2 short-read aligner. Yes No Yes Yes Free, GPL
CUSHAW3 Sensitive and accurate base-space and color-space short-read alignment with hybrid seeding Yes No Yes Yes Free, GPL [41] 2012
drFAST Read mapping alignment software that implements cache obliviousness to minimize main/cache memory transfers like mrFAST and mrsFAST, however designed for the SOLiD sequencing platform (color space reads). It also returns all possible map locations for improved structural variation discovery. Yes Yes, for structural variation Yes No Free, BSD
ELAND Implemented by Illumina. Includes ungapped alignment with a finite read length.
ERNE Extended Randomized Numerical alignEr for accurate alignment of NGS reads. It can map bisulfite-treated reads. Yes Low quality bases trimming Yes Multithreading and MPI-enabled Free, GPL 3
GASSST Finds global alignments of short DNA sequences against large DNA banks Multithreading CeCILL version 2 License. [42] 2011
GEM High-quality alignment engine (exhaustive mapping with substitutions and indels). More accurate and several times faster than BWA or Bowtie 1/2. Many standalone biological applications (mapper, split mapper, mappability, and other) provided. Yes Yes Yes Yes Free, GPL3 [43] 2012
Genalice MAP Ultra fast and comprehensive NGS read aligner with high precision and small storage footprint. Yes Low quality bases trimming Yes Yes Proprietary, commercial
Geneious Assembler Fast, accurate overlap assembler with the ability to handle any combination of sequencing technology, read length, any pairing orientations, with any spacer size for the pairing, with or without a reference genome. Yes Proprietary, commercial
GensearchNGS Complete framework with user-friendly GUI to analyse NGS data. It integrates a proprietary high quality alignment algorithm and plug-in ability to integrate various public aligner into a framework allowing to import short reads, align them, detect variants, and generate reports. It is made for resequencing projects, namely in a diagnostic setting. Yes No Yes Yes Proprietary, commercial
GMAP and GSNAP Robust, fast short-read alignment. GMAP: longer reads, with multiple indels and splices (see entry above under Genomics analysis); GSNAP: shorter reads, with one indel or up to two splices per read. Useful for digital gene expression, SNP and indel genotyping. Developed by Thomas Wu at Genentech. Used by the National Center for Genome Resources (NCGR) in Alpheus. Yes Yes Yes Yes Proprietary, freeware for academic and noncommercial use
GNUMAP Accurately performs gapped alignment of sequence data obtained from next-generation sequencing machines (specifically of Solexa-Illumina) back to a genome of any size. Includes adaptor trimming, SNP calling and Bisulfite sequence analysis. Yes, also supports Illumina *_int.txt and *_prb.txt files with all 4 quality scores for each base Multithreading and MPI-enabled [44] 2009
HIVE-hexagon Uses a hash table and bloom matrix to create and filter potential positions on the genome. For higher efficiency uses cross-similarity between short reads and avoids realigning non unique redundant sequences. It is faster than Bowtie and BWA and allows indels and divergent sensitive alignments on viruses, bacteria, and more conservative eukaryotic alignments. Yes Yes Yes Yes Proprietary, freeware for academic and noncommercial users registered to HIVE deployment instance [45] 2014
IMOS Improved Meta-aligner and Minimap2 On Spark. A long read distributed aligner on Apache Spark platform with linear scalability w.r.t. single node execution. Yes Yes Yes Free
Isaac Fully uses all the computing power available on one server node; thus, it scales well over a broad range of hardware architectures, and alignment performance improves with hardware abilities Yes Yes Yes Yes Free, GPL
LAST Uses adaptative seeds and copes more efficiently with repeat-rich sequences (e.g. genomes). For example: it can align reads to genomes without repeat-masking, without becoming overwhelmed by repetitive hits. Yes Yes Yes Yes Free, GPL [46] 2011
MAQ Ungapped alignment that takes into account quality scores for each base. Free, GPL
mrFAST, mrsFAST Gapped (mrFAST) and ungapped (mrsFAST) alignment software that implements cache obliviousness to minimize main/cache memory transfers. They are designed for the Illumina sequencing platform and they can return all possible map locations for improved structural variation discovery. Yes Yes, for structural variation Yes No Free, BSD
MOM MOM or maximum oligonucleotide mapping is a query matching tool that captures a maximal length match within the short read. Yes
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
MPscan Fast aligner based on a filtration strategy (no indexing, use q-grams and Backward Nondeterministic DAWG Matching) [47] 2009
Novoalign & NovoalignCS Gapped alignment of single end and paired end Illumina GA I & II, ABI Colour space & ION Torrent reads. High sensitivity and specificity, using base qualities at all steps in the alignment. Includes adapter trimming, base quality calibration, Bi-Seq alignment, and options for reporting multiple alignments per read. Use of ambiguous IUPAC codes in reference for common SNPs can improve SNP recall and remove allelic bias. Yes Yes Yes Multi-threading and MPI versions available with paid license Proprietary, freeware single threaded version for academic and noncommercial use
NextGENe Developed for use by biologists performing analysis of next generation sequencing data from Roche Genome Sequencer FLX, Illumina GA/HiSeq, Life Technologies Applied BioSystems’ SOLiD System, PacBio and Ion Torrent platforms. Yes Yes Yes Yes Proprietary, commercial
NextGenMap Flexible and fast read mapping program (twice as fast as BWA), achieves a mapping sensitivity comparable to Stampy. Internally uses a memory efficient index structure (hash table) to store positions of all 13-mers present in the reference genome. Mapping regions where pairwise alignments are required are dynamically determined for each read. Uses fast SIMD instructions (SSE) to accelerate alignment calculations on CPU. If available, alignments are computed on GPU (using OpenCL/CUDA) further reducing runtime 20-50%. Yes No Yes Yes, POSIX Threads, OpenCL/CUDA, SSE Free [48] 2013
Omixon Variant Toolkit Includes highly sensitive and highly accurate tools for detecting SNPs and indels. It offers a solution to map NGS short reads with a moderate distance (up to 30% sequence divergence) from reference genomes. It poses no restrictions on the size of the reference, which, combined with its high sensitivity, makes the Variant Toolkit well-suited for targeted sequencing projects and diagnostics. Yes Yes Yes Yes Proprietary, commercial
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 one CPU. It refines the originally proposed QPALMA approach. Yes Free, GPL
Partek Flow For use by biologists and bioinformaticians. It supports ungapped, gapped and splice-junction alignment from single and paired-end reads from Illumina, Life technologies Solid TM, Roche 454 and Ion Torrent raw data (with or without quality information). It integrates powerful quality control on FASTQ/Qual level and on aligned data. Additional functionality include trimming and filtering of raw reads, SNP and InDel detection, mRNA and microRNA quantification and fusion gene detection. Yes Yes Yes Multiprocessor-core, client-server installation possible Proprietary, commercial, free trial version
PASS Indexes the genome, then extends seeds using pre-computed alignments of words. Works with base space, color space (SOLID), and can align genomic and spliced RNA-seq reads. Yes Yes Yes Yes Proprietary, freeware for academic and noncommercial use
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 Free, GPL [49]
PRIMEX Indexes the genome with a k-mer lookup table with full sensitivity up to an adjustable number of mismatches. It is best for mapping 15-60 bp sequences to a genome. No No Yes No, multiple processes per search [1] 2003
QPalma Can use 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 Free, GPL 2
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. Free, LGPL
REAL, cREAL REAL is an efficient, accurate, and sensitive tool for aligning short reads obtained from next-generation sequencing. The programme can handle an enormous amount of single-end reads generated by the next-generation Illumina/Solexa Genome Analyzer. cREAL is a simple extension of REAL for aligning short reads obtained from next-generation sequencing to a genome with circular structure. Yes Yes Free, GPL
RMAP Can map reads with or without error probability information (quality scores) and supports paired-end reads or bisulfite-treated read mapping. There are no limitations on read length or number of mismatches. Yes Yes Yes Free, GPL 3
rNA A randomized Numerical Aligner for Accurate alignment of NGS reads Yes Low quality bases trimming Yes Multithreading and MPI-enabled Free, GPL 3
RTG Investigator Extremely fast, tolerant to high indel and substitution counts. Includes full read alignment. Product includes comprehensive pipelines for variant detection and metagenomic analysis with any combination of Illumina, Complete Genomics and Roche 454 data. Yes Yes, for variant calling Yes Yes Proprietary, freeware for individual investigator use
Segemehl Can handle insertions, deletions, mismatches; uses enhanced suffix arrays Yes No Yes Yes Proprietary, freeware for noncommercial use [50] 2009
SeqMap Up to 5 mixed substitutions and insertions-deletions; various tuning options and input-output formats Proprietary, freeware for academic and noncommercial use
Shrec Short read error correction with a suffix tree data structure Yes, Java
SHRiMP Indexes the reference genome as of version 2. Uses masks to generate possible keys. Can map ABI SOLiD color space reads. Yes Yes Yes Yes, OpenMP Free, [[BSD licenses Free, BSD]] derivative

[51] [52]

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. Yes Yes No No [53][54] 2009-2010
SOAP, SOAP2, SOAP3, SOAP3-dp SOAP: robust with a small (1-3) number of gaps and mismatches. Speed improvement over BLAT, uses a 12 letter hash table. SOAP2: using bidirectional BWT to build the index of reference, and it is much faster than the first version. SOAP3: GPU-accelerated version that could find all 4-mismatch alignments in tens of seconds per one million reads. SOAP3-dp, also GPU accelerated, supports arbitrary number of mismatches and gaps according to affine gap penalty scores. Yes No Yes, SOAP3-dp Yes, POSIX Threads; SOAP3, SOAP3-dp need GPU with CUDA support Free, GPL [55][56]
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 Free, GPL
SparkBWA Integrates the Burrows–Wheeler Aligner (BWA) on an Apache Spark framework running atop Hadoop. Version 0.2 of October 2016, supports the algorithms BWA-MEM, BWA-backtrack, and BWA-ALN. All of them work with single-reads and paired-end reads. Yes Low quality bases trimming Yes Yes Free, GPL 3 [57] 2016
SSAHA, SSAHA2 Fast for a small number of variants Proprietary, freeware for academic and noncommercial use
Stampy For Illumina reads. High specificity, and sensitive for reads with indels, structural variants, or many SNPs. Slow, but speed increased dramatically by using BWA for first alignment pass. Yes Yes Yes No Proprietary, freeware for academic and noncommercial use [58] 2010
SToRM For Illumina or ABI SOLiD reads, with SAM native output. Highly sensitive for reads with many errors, indels (full from 0 to 15, extended support otherwise). Uses spaced seeds (single hit) and a very fast SSE-SSE2-AVX2-AVX-512 banded alignment filter. For fixed-length reads only, authors recommend SHRiMP2 otherwise. No Yes Yes Yes, OpenMP Free [59] 2010
Subread, Subjunc Superfast and accurate read aligners. Subread can be used to map both gDNA-seq and RNA-seq reads. Subjunc detects exon-exon junctions and maps RNA-seq reads. They employ a novel mapping paradigm named seed-and-vote. Yes Yes Yes Yes Free, GPL 3
Taipan De-novo assembler for Illumina reads Proprietary, freeware for academic and noncommercial use
UGENE Visual interface both for Bowtie and BWA, and an embedded aligner Yes Yes Yes Yes Free, GPL
VelociMapper FPGA-accelerated reference sequence alignment mapping tool from TimeLogic. Faster than Burrows–Wheeler transform-based algorithms like BWA and Bowtie. Supports up to 7 mismatches and/or indels with no performance penalty. Produces sensitive Smith–Waterman gapped alignments. Yes Yes Yes Yes Proprietary, commercial
XpressAlign FPGA based sliding window short read aligner which exploits the embarrassingly parallel property of short read alignment. Performance scales linearly with number of transistors on a chip (i.e. performance guaranteed to double with each iteration of Moore's Law without modification to algorithm). Low power consumption is useful for datacentre equipment. Predictable runtime. Better price/performance than software sliding window aligners on current hardware, but not better than software BWT-based aligners currently. Can manage large numbers (>2) of mismatches. Will find all hit positions for all seeds. Single-FPGA experimental version, needs work to develop it into a multi-FPGA production version. Proprietary, freeware for academic and noncommercial use
ZOOM 100% sensitivity for a reads between 15 and 240 bp with practical mismatches. Very fast. Support insertions and deletions. Works with Illumina & SOLiD instruments, not 454. Yes (GUI), no (CLI) Proprietary, commercial [60]

See also[edit]


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