Table 1.
Summary of algorithms and features of the examined read alignment methods. We surveyed 107 alignment tools published from 1988 to 2020 (indicated in column “Year of publication”). The table is sorted by year of publication, and then grouped according to the area(s) of application (indicated in column “Application”) within each year. In column “Indexing,” we document the algorithms used to index the genome (the first step in read alignment). In column “Global Positioning,” we document the algorithms used to determine a global position of the read in the reference genome (the second step). In column “Pairwise alignment,” we document the algorithm used to determine the similarity between the read and the corresponding region of the reference genome (the last step). SW, NW, HD, and DP stand for Smith-Waterman algorithm, Needleman-Wunsch algorithm, Hamming distance, and dynamic programming, respectively. In column “Wrapper,” we document the read alignment algorithms that are built on top of other read alignment tools. Finally, we report the maximum read length tested in the corresponding paper in column “Max. Read Length Tested in the Paper (bp).” The tested read length in each paper is not necessarily the maximum read length that each tool can handle
| Aligner | URL | Year of publication | Application | Indexing | Global Positioning | Pairwise alignment | Wrapper | Max. read length tested in the paper (bp) | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Fix length seed | Spaced seed | Seed chaining | ||||||||
| FASTA [30] | https://fasta.bioch.virginia.edu/fasta_www2/fasta_list2.shtml | 1988 | DNA | Hashing | Y | N | Y | SW and NW | N | 1500 |
| BLAST [31] | https://blast.ncbi.nlm.nih.gov/Blast.cgi | 1990 | DNA | Hashing | Y | N | Y | Non-DP Heuristic | N | 73360 |
| Gapped BLAST [32] | https://blast.ncbi.nlm.nih.gov/Blast.cgi | 1997 | DNA | Hashing | Y | N | Y | SW | N | 246 |
| SSAHA [33] | https://www.sanger.ac.uk/science/tools/ssaha | 2001 | DNA | Hashing | Y | N | N | NW | N | 500 |
| PatternHunter [34–37] | https://www.bioinfor.com/ | 2002 | DNA | Hashing | Y | Y | Y | Non-DP heuristic | N | 500 |
| BLAT [38] | https://genome.ucsc.edu/cgi-bin/hgBlat | 2002 | DNA | Hashing | Y | N | Y | Non-DP heuristic | N | 500 |
| BLASTZ [39] | https://www.bx.psu.edu/miller_lab/ | 2003 | DNA | Hashing | Y | N | N | SW | Y | 3000 |
| C4 [40] | https://github.com/nathanweeks/exonerate | 2005 | DNA | Hashing | Y | N | Y | Sparse DP | N | N/A |
| GMAP [41] | https://github.com/juliangehring/GMAP-GSNAP | 2005 | DNA | Hashing | N | N | Y | NW | N | N/A |
| BWT-SW [42] | https://github.com/mruffalo/bwt-sw | 2008 | DNA | BWT | Y | N | N | SW | N | 2000 |
| MAQ [43] | http://maq.sourceforge.net/maq-man.shtml | 2008 | DNA | Hashing | Y | Y | N | SW | N | 63 |
| RMAP [44] | https://github.com/smithlabcode/rmap | 2008 | DNA | Hashing | Y | N | N | HD | N | 36 |
| SOAP [45] | https://github.com/ShujiaHuang/SOAPaligner | 2008 | DNA | Hashing | Y | N | N | Non-DP heuristic | N | 50 |
| SOCS [46] | http://socs.biology.gatech.edu/ | 2008 | DNA | Hashing | Y | N | N | Rabin-Karp Algorithm | N | 35 |
| SeqMap [47] | http://www-personal.umich.edu/~jianghui/seqmap/ | 2008 | DNA | Hashing | Y | N | N | Non-DP Heuristic | N | 30 |
| ZOOM [48] | http://www.bioinfor.com/zoom-1-3-gui-release-next-gen-seq/ | 2008 | DNA | Hashing | Y | Y | N | SW | N | 36 |
| QPALMA [49, 50] | http://www.raetschlab.org/suppl/qpalma | 2008 | RNA-Seq | Suffix array | Y | N | Y | SW | Y | 36 |
| BRAT [51] | http://compbio.cs.ucr.edu/brat/ | 2009 | BS-Seq | Hashing | Y | N | N | HD | N | 26 |
| BSMAP [52] | https://github.com/genome-vendor/bsmap | 2009 | BS-Seq | Hashing | Y | N | N | HD | N | 32 |
| BFAST [53] | https://github.com/nh13/BFAST/ | 2009 | DNA | Hashing | N | Y | N | SW | N | 55 |
| BWA [54] | https://github.com/lh3/bwa | 2009 | DNA | BWT-FM | N | N | N | Semi-Global | N | 125 |
| Bowtie [55] | http://bowtie-bio.sourceforge.net/manual.shtml | 2009 | DNA | BWT-FM | Y | N | N | HD | N | 76 |
| CloudBurst [56] | https://sourceforge.net/projects/cloudburst-bio/ | 2009 | DNA | Hashing | Y | N | N | Landau-Vishkin | N | 36 |
| GNUMAP [57] | https://github.com/byucsl/gnumap | 2009 | DNA | Hashing | Y | N | Y | NW | N | 36 |
| GenomeMapper [58] | http://1001genomes.org/software/genomemapper_singleref.html | 2009 | DNA | Hashing | Y | N | Y | NW | N | 200 |
| MOM [59] | https://github.com/hugheaves/MOM | 2009 | DNA | Hashing | Y | N | N | HD | N | 40 |
| PASS [60] | http://pass.cribi.unipd.it/cgi-bin/pass.pl | 2009 | DNA | Hashing | Y | N | Y | NW | N | 32 |
| PerM [61] | https://code.google.com/archive/p/perm/downloads | 2009 | DNA | Hashing | Y | Y | N | HD | N | 47 |
| RazerS [62] | https://github.com/seqan/seqan/tree/master/apps/razers | 2009 | DNA | Hashing | Y | Y | Y | Myers Bit Vector | N | 76 |
| SHRiMP [63] | http://compbio.cs.toronto.edu/shrimp/ | 2009 | DNA | Hashing | N | N | N | SW | N | 35 |
| SOAP2 [64] | https://github.com/ShujiaHuang/SOAPaligner | 2009 | DNA | BWT-FM | Y | N | N | SW | N | 44 |
| Slider [65] | http://www.bcgsc.ca/platform/bioinfo/software/slider | 2009 | DNA | Hashing | Y | N | N | HD | N | 36 |
| segemehl [66] | https://www.bioinf.uni-leipzig.de/Software/segemehl/ | 2009 | DNA | Suffix array | N | N | Y | SW | N | 35 |
| TopHat [67] | https://ccb.jhu.edu/software/tophat/index.shtml | 2009 | RNA-Seq | BWT-FM | Y | N | N | HD | Y | 42 |
| BS-Seeker [68] | http://pellegrini-legacy.mcdb.ucla.edu/bs_seeker/BS_Seeker.html | 2010 | BS-Seq | BWT-FM | Y | N | N | HD | Y | 36 |
| BWA-SW [54] | https://github.com/lh3/bwa | 2010 | DNA | BWT-FM | N | N | N | SW | N | 10000 |
| GASSST [35] | http://www.irisa.fr/symbiose/projects/gassst/ | 2010 | DNA | Hashing | Y | Y | Y | Semi-Global | N | 500 |
| GSNAP [37] | https://github.com/juliangehring/GMAP-GSNAP | 2010 | DNA | Hashing | Y | N | Y | Non-DP Heuristic | N | 100 |
| SMALT [69] | https://github.com/rcallahan/smalt | 2010 | DNA | Hashing | Y | N | Y | SW | N | 150 |
| Slider II [70] | http://www.bcgsc.ca/platform/bioinfo/software/SliderII | 2010 | DNA | Hashing | Y | N | N | HD | Y | 42 |
| VMATCH [71] | http://www.vmatch.de/ | 2010 | DNA | Suffix array | Y | N | Y | SW | Y | N/A |
| mrsFAST [72] | https://github.com/sfu-compbio/mrsfast | 2010 | DNA | Hashing | Y | N | N | HD | N | 100 |
| MapSplice [73] | https://github.com/LiuBioinfo/MapSplice | 2010 | RNA-Seq | BWT-FM | Y | N | N | HD | Y | 100 |
| MicroRazerS [74] | https://github.com/seqan/seqan/tree/master/apps/micro_razers | 2010 | RNA-Seq | Hashing | Y | N | Y | HD | N | 36 |
| SpliceMap [75] | http://web.stanford.edu/group/wonglab/SpliceMap/ | 2010 | RNA-Seq | Hashing | Y | N | N | HD | Y | 50 |
| Supersplat [76] | http://mocklerlab.org/tools/1/manual | 2010 | RNA-Seq | Hashing | N | N | N | NA | N | 36 |
| Bismark [77] | https://github.com/FelixKrueger/Bismark | 2011 | BS-Seq | BWT-FM | Y | N | Y | SW & NW | Y | 50 |
| LAST [78] | http://last.cbrc.jp/ | 2011 | DNA/BS-Seq/RNA | Suffix array | N | Y | N | SW & NW | N | 105 |
| DynMap [79] | https://dl.acm.org/citation.cfm?id=2147845&dl=ACM&coll=DL | 2011 | DNA | Hashing | Y | N | N | NW | N | 52 |
| SHRiMP2 [80] | http://compbio.cs.toronto.edu/shrimp/ | 2011 | DNA | Hashing | Y | Y | Y | SW | N | 75 |
| SNAP [81] | http://snap.cs.berkeley.edu/ | 2011 | DNA | Hashing | Y | N | N | NW | N | 10000 |
| Stampy [82] | https://www.well.ox.ac.uk/project-stampy | 2011 | DNA | Hashing | Y | N | N | NW | N | 4500 |
| TMAP | https://github.com/iontorrent/TS/tree/master/Analysis/TMAP | 2011 | DNA | BWT-FM | N | N | Y | SW | N | N/A |
| X-Mate [83] | http://grimmond.imb.uq.edu.au/X-MATE/ | 2011 | DNA | Hashing | N | N | N | Non-DP Heuristic | N | 50 |
| SOAPSplice [84] | http://soap.genomics.org.cn/soapsplice.html | 2011 | RNA-Seq | BWT-FM | Y | N | N | Non-DP Heuristic | N | 150 |
| BRAT-BW [51] | http://compbio.cs.ucr.edu/brat/ | 2012 | BS-Seq | BWT-FM | N | N | N | HD | N | 62 |
| BLASR [85] | https://github.com/mchaisso/blasr/ | 2012 | DNA | Suffix array | Y | N | Y | NW | N | 8000 |
| Batmis [86] | https://code.google.com/archive/p/batmis/ | 2012 | DNA | BWT-ST | Y | N | N | HD | N | 100 |
| Bowtie2 [87] | http://bowtie-bio.sourceforge.net/bowtie2 | 2012 | DNA | BWT-FM | Y | N | Y | SW & NW | N | 400 |
| GEM [88] | https://github.com/smarco/gem3-mapper | 2012 | DNA | BWT-FM | N | N | Y | SW & NW | N | 150 |
| RazerS3 [89] | https://github.com/seqan/seqan/tree/master/apps/razers3 | 2012 | DNA | Hashing | Y | Y | Y | Banded Myers Bit Vector | N | 800 |
| SeqAlto [90] | https://web.stanford.edu/group/wonglab/seqalto/ | 2012 | DNA | Hashing | Y | N | N | NW | N | 200 |
| SplazerS [91] | https://github.com/seqan/seqan/blob/master/apps/splazers/README | 2012 | DNA | Hashing | Y | N | Y | Banded Myers Bit Vector | N | 150 |
| WHAM [92] | http://pages.cs.wisc.edu/~jignesh/wham/ | 2012 | DNA | Hashing | Y | N | N | NW | N | 74 |
| YAHA [93] | https://github.com/GregoryFaust/yaha | 2012 | DNA | Hashing | Y | N | Y | SW | N | 10000 |
| OSA [94] | http://www.arrayserver.com/wiki/index.php?title=OSA | 2012 | RNA-Seq | Hashing | Y | N | N | NA | N | 100 |
| Passion [95] | https://trac.nbic.nl/passion/ | 2012 | RNA-Seq | Hashing | Y | N | Y | SW | Y | 75 |
| BS-Seeker2 [96] | https://github.com/BSSeeker/BSseeker2 | 2013 | BS-Seq | BWT-FM | Y | N | Y | SW & NW | Y | 250 |
| Subread [97] | http://subread.sourceforge.net/ | 2013 | DNA/RNA-Seq | Hashing | Y | Y | Y | SW | N | 202 |
| BWA-MEM [98] | https://github.com/lh3/bwa | 2013 | DNA | BWT-FM | N | N | Y | SW & NW | N | 650 |
| Masai [99] | http://www.seqan.de/projects/masai | 2013 | DNA | Suffix tree | N | N | Y | Banded Myers Bit Vector | N | 150 |
| NextGenMap [100] | http://cibiv.github.io/NextGenMap/ | 2013 | DNA | Hashing | Y | N | N | SW & NW | N | 250 |
| SRmapper [101] | http://www.umsl.edu/~wongch/software.html | 2013 | DNA | Hashing | Y | N | N | HD | N | 100 |
| mrFAST [102] | https://github.com/BilkentCompGen/mrfast | 2013 | DNA | Hashing | Y | N | N | Semi-Global | N | 180 |
| CRAC [103] | http://crac.gforge.inria.fr/ | 2013 | RNA-Seq | BWT-FM | Y | N | N | Non-DP Heuristic | N | 200 |
| STAR [104] | https://github.com/alexdobin/STAR | 2013 | RNA-Seq | Suffix array | N | N | Y | SW | N | 5000 |
| TopHat2 [105] | https://ccb.jhu.edu/software/tophat/index.shtml | 2013 | RNA-Seq | BWT-FM | Y | N | Y | SW & NW | Y | 101 |
| Subjunc [106] | http://subread.sourceforge.net/ | 2013 | RNA-seq | Hashing | Y | Y | Y | NW | N | 202 |
| BWA-PSSM [107] | http://bwa-pssm.binf.ku.dk/ | 2014 | DNA | BWT-FM | Y | N | N | SW | Y | 100 |
| CUSHAW3 [108] | http://cushaw3.sourceforge.net/homepage.htm#latest | 2014 | DNA | BWT-FM | Y | N | Y | SW & Semi-Global | N | 100 |
| Hobbes2 [109] | https://hobbes.ics.uci.edu/download.shtml | 2014 | DNA | Hashing | Y | N | Y | Banded Myers Bit Vector | N | 100 |
| MOSAIK [110] | https://github.com/wanpinglee/MOSAIK | 2014 | DNA | Hashing | Y | N | N | SW | N | 100 |
| hpg-Aligner [111] | https://github.com/opencb/hpg-aligner | 2014 | DNA | Suffix array | N | N | Y | SW | N | 5000 |
| mrsFAST-Ultra [112] | https://github.com/sfu-compbio/mrsfast | 2014 | DNA | Hashing | Y | N | N | HD | N | 100 |
| JAGuaR [113] | http://www.bcgsc.ca/platform/bioinfo/software/jaguar | 2014 | RNA-Seq | BWT-FM | Y | N | N | SW | Y | 100 |
| ContextMap 2 [114] | http://www.bio.ifi.lmu.de/ContextMap | 2015 | RNA-Seq | BWT-FM | Y | N | Y | SW & NW | Y | 76 |
| HISAT [115] | http://www.ccb.jhu.edu/software/hisat/index.shtml | 2015 | RNA-Seq | BWT-FM | Y | N | N | Non-DP Heuristic | N | 100 |
| ERNE 2 [116] | http://erne.sourceforge.net/ | 2016 | DNA/BS-Seq | BWT-FM + hashing | Y | N | N | HD | N | 100 |
| GraphMap [117] | https://github.com/isovic/graphmap | 2016 | DNA | Hashing | Y | Y | Y | Semi-global | N | 9000 |
| NanoBLASTer [118] | https://github.com/ruhulsbu/NanoBLASTer | 2016 | DNA | Hashing | Y | N | Y | NW | N | 7040 |
| minimap [119] | https://github.com/lh3/minimap | 2016 | DNA | Hashing | Y | N | N | N/A | N | 13000 |
| rHAT [120] | https://github.com/dfguan/rHAT | 2016 | DNA | Hashing | Y | N | Y | SW | N | 8000 |
| KART [121] | https://github.com/hsinnan75/KART | 2017 | DNA | BWT-FM | N | N | Y | NW | N | 7118 |
| LAMSA [122] | https://github.com/hitbc/LAMSA | 2017 | DNA | BWT-FM + hashing | Y | N | Y | Sparse DP | Y | 100000 |
| DART [123] | https://github.com/hsinnan75/DART | 2017 | RNA-Seq | BWT-FM | N | N | Y | NW | N | 251 |
| minimap2 [124] | https://github.com/lh3/minimap2 | 2018 | DNA/RNA-Seq | Hashing | Y | N | Y | NW | N | 11628 |
| DREAM-Yara [125] | https://gitlab.com/pirovc/dream_yara/ | 2018 | DNA | BWT-FM | Y | N | N | Banded Myers Bit Vector | Y | 150 |
| MUMmer4 [126] | https://github.com/mummer4/mummer | 2018 | DNA | Suffix array | Y | N | Y | SW | Y | 7821 |
| NGMLR [127] | https://github.com/philres/ngmlr | 2018 | DNA | Hashing | Y | N | Y | SW | N | 50000 |
| lordFAST [128] | https://github.com/vpc-ccg/lordfast | 2018 | DNA | BWT-FM + hashing | N | N | Y | SW & NW | N | 35489 |
| BatMeth2 [129] | https://github.com/GuoliangLi-HZAU/BatMeth2/ | 2019 | BS-Seq | BWT-FM | Y | N | Y | SW & NW | N | 125 |
| GraphMap2 [130] | https://github.com/lbcb-sci/graphmap2 | 2019 | DNA/RNA-Seq | Hashing | Y | Y | Y | Semi-global | N | 9000 |
| Magic-BLAST [131] | https://github.com/ncbi/magicblast | 2019 | DNA/RNA-Seq | Hashing | Y | N | N | Non-DP Heuristic | N | 90000 |
| BWA-MEM2 [132] | https://github.com/bwa-mem2/bwa-mem2 | 2019 | DNA | BWT-FM | N | N | Y | SW | N | 650 |
| HISAT2 [133] | https://ccb.jhu.edu/software/hisat2/index.shtml | 2019 | DNA | BWT-FM | Y | N | N | Non-DP Heuristic | N | 100 |
| deSALT [134] | https://github.com/hitbc/deSALT | 2019 | RNA-seq | Hashing | Y | N | Y | SW | N | 8000 |
| conLSH [135] | https://www.dropbox.com/s/3jcu4i240kyu2tc/source%20code%20conLSH_bio.tar.gz?dl=0 | 2020 | DNA | Hashing | Y | N | Y | Sparse DP | N | 8000 |