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Fast and accurate long-read alignment with Burrows-Wheeler transform.
Open accessAbstract
Motivation: Many programs for aligning short sequencing reads to a reference genome have been developed in the last 2 years. Most of them are very efficient for short reads but inefficient or not applicable for reads >200 bp because the algorithms are heavily and specifically tuned for short queries with low sequencing error rate. However, some sequencing platforms already produce longer reads and others are expected to become available soon. For longer reads, hashing-based software such as BLAT and SSAHA2 remain the only choices. Nonetheless, these methods are substantially slower than short-read aligners in terms of aligned bases per unit time. Results: We designed and implemented a new algorithm, Burrows-Wheeler Aligner's Smith-Waterman Alignment (BWA-SW), to align long sequences up to 1 Mb against a large sequence database (e.g. the human genome) with a few gigabytes of memory. The algorithm is as accurate as SSAHA2, more accurate than BLAT, and is several to tens of times faster than both. Availability: http://bio-bwa.sourceforge.net Contact: rd@sanger.ac.uk
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![Fig. 1. Prefix trie and prefix DAWG of string ‘GOOGOL’. (A) Prefix trie. Symbol ‘∧’ marks the start of a string. The two numbers in a node gives the SA interval of the node. (B) Prefix DAWG constructed by collapsing nodes with the identical SA interval. For example, in the prefix trie, three nodes has SA interval [4, 4]. Their parents have interval [1, 2], [1, 2] and [1, 1], respectively. In the prefix DAWG, the [4, 4] node thus has parents [1, 2] and [1, 1]. Node [4, 4] represents three strings ‘OG’, ‘OGO’ and ‘OGOL’ with the first two strings being the prefix of ‘OGOL’. (A) is modified from Figure 1 in Li and Durbin (2009).](/paper-figures/1df6af5164514755b0a07be87022bd5e/fast-and-accurate-long-read-alignment-with-burrows-wheeler-transform-figure-1.jpg)
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“Software confirmed to be working for this approach include (but are not limited to) Bowtie2 11, BWA 12, HISAT2 13, STAR 14 or any tool wrapping one of these aligners.”
From SNPsplit: Allele-specific splitting of alignments between genomes with known SNP genotypes (2016) · cites this paper as [12]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Mapping reads to specific genes is relatively straightforward with the bioinformatics tools available today [10-13], but using these tools to distinguish between reads derived from alternative alleles of the same gene remains challenging [9].”
From Sources of bias in measures of allele-specific expression derived from RNA-seq data aligned to a single reference genome (2013) · cites this paper as [11]
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Self-citationFast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
Self-citationUltrafast and memory-efficient alignment of short DNA sequences to the human genome.
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Influential<tt>BLAT</tt> —The <tt>BLAST</tt> -Like Alignment Tool
Kent, W. J. (2002) · Genome Research · doi:10.1101/gr.229202 · Cited by 8,480 · cited 1×
“…and PatternHunter (Ma et al ., 2002), greatly speeding up matching capillary sequencing technologies arrived that generated millions of short (<100bp) reads, a variety of new algorithms were developed which were 10–1000 times faster, including SOAP (Li,R. et al 2008), MAQ (Li,H. et al ., 2009).”
A Greedy Algorithm for Aligning DNA Sequences
Zhang, Z., Schwartz, S., Wagner, L., & Miller, W. (2000) · Journal of Computational Biology · doi:10.1089/10665270050081478 · Cited by 5,459 · cited 1×
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SOAP: Short oligonucleotide alignment program
Li, R., Li, Y., Kristiansen, K., & Wang, J. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn025 · Cited by 3,597
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- Burrows, 1994, A block-sorting lossless data compression algorithm
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Protective TMEM106B-rs3173615 delays age at onset in GRN mutation carriers
Pagano, L., Saraceno, C., Geviti, A., Fostinelli, S., Facconi, A., Laganà, V., Giacomucci, G., Cotelli, M. S., Ingannato, A., Bagnoli, S., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03653-w
“The remaining high-quality reads were then aligned to the hg38 reference genome using BWA-MEM (version 0.7.17-r1188) [34].”
InfluentialGenomic insights into the probiotic potential of Bacillus velezensis D-18 for aquaculture
Monzón-Atienza, L., Felipe, Á. L., Cabrera-Guerle, N., Gómez-Mercader, A., Carlino-Costa, C., Ramos-Vivas, J., Zhang, M.-L., Montero, D., Acosta, F., & Galindo-Villegas, J. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1824441
“7.17) (Li and Durbin, 2010), and duplicate reads were removed with Sambamba (v0.”
InfluentialXu, K., Zhang, K., Li, J., Huang, Y.-X., Gou, J., Zhou, J.-L., Wang, Y., Chen, F.-F., & Xiao, P. (2026) · BMC Genomics · doi:10.1186/s12864-026-12943-0
“7.17 [15].”
InfluentialUprety, T., Goehring, L., Rozhbayani, A., Meyer, A., Todd, S., Abdelrazek, S., Lahmers, K., & Erol, E. (2026) · Microbiology Resource Announcements · doi:10.1128/mra.01347-25
Gwayi, S., Tomoka, T., Chimusa, E. R., Fedoriw, G., & Kumwenda, B. (2026) · African Journal of Laboratory Medicine · doi:10.4102/ajlm.v15i1.3073
“28 Variant calling was performed on recalibrated bases via Genome Analysis Toolkit Haplotype Caller, followed by joint genotype calling on the individual sample generating a genotype Variant Call Format file.”
A novel hemizygous missense variant in the BEND2 gene is associated with nonobstructive azoospermia
Luo, C.-H., Yu, Z.-Q., Wang, H.-Y., Zhou, H., Wu, Y.-H., Shao, L.-F., Liu, H.-C., Zhan, J.-F., Xie, C., Ke, S.-W., et al. (2026) · Asian Journal of Andrology · doi:10.4103/aja2025122
Gil-Polo, A., Bledsoe, R. B., Calvert, M. B., Cherry, L., Epstein, B., Fudge, R., Harris, J. E., Tiffin, P., & Burghardt, L. (2026) · mBio · doi:10.1128/mbio.03793-25
“7.17; [37]; NCBI BioProject: PRJNA388336).”
InfluentialZhang, N., Li, L., Ta, K.-W., Shi, C., Seim, I., Zhang, Y., Zhang, W.-J., Cui, Z., Xiang, X., Jia, L.-M., et al. (2026) · bioRxiv · doi:10.64898/2026.05.06.723128
A chromosome-level whole genome of Red mahseer (Tor sinensis)
Que, Y.-F., Li, W.-T., Wu, J., Hu, X.-K., Wang, E., Dong, W.-W., & Zhu, B. (2026) · Scientific Data · doi:10.1038/s41597-026-07385-y
“Scaffolding was performed using the 3D-DNA pipeline 22,23 , which clustered 158 contigs into 50 chromosome-scale groups.”
Telomere-to-telomere Genome Assembly of Equus kiang (Tibetan wild donkey)
Zheng, Y., Hu, Y., 索佳佳, Wang, W., Wang, Y., Cao, L., Sun, P., 张麦收, Zhao, M., Yang, W., et al. (2026) · Scientific Data · doi:10.1038/s41597-026-07355-4
“7.17) 36 .”
InfluentialClarke, S., Allen, I., Ravix, J., Marção, M., Carcanholo, F., Doughan, A., Sanchez-Covarrubias, A. P., Cornwall, D., Harrison, S., Volmar, C., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-51649-x
Ancient DNA reveals pig domestication history in Northeastern China
Tao, H.-L., Zheng, M., Xiao, B., Song, S.-W., Xing, F., Guan, R., Zhu, Y., Jiang, S., Lai, X.-L., Yuan, J.-X., et al. (2026) · Journal of Genetic Engineering and Biotechnology · doi:10.1016/j.jgeb.2026.100704
A retrospective analysis of cystic enteropathy in Alabama broilers
Lockyear, O., Álvarez-Narváez, S., Conrad, S. J., Carnaccini, S., Huber, L., & Walz, H. (2026) · Avian Pathology · doi:10.1080/03079457.2026.2651255
“7.17 (Li & Durbin, 2010), SAMtools V1.”
InfluentialMutational landscape in the precancerous stages of sporadic colorectal cancer.
Valíčková, A., Urbanova, M., Horák, J., Jungwirth, J., Kral, J., Hucl, T., Makajevová, V., Summerova, S., Kohout, P., Matěj, R., et al. (2026) · Oncology Letters · doi:10.3892/ol.2026.15634
Shifflett, S. A., Weyer, E., MacDonald, M. L., & Ellis, V. A. (2026) · Molecular Genetics and Genomics · doi:10.1007/s00438-026-02427-x
“Trimmed forward and reverse reads were mapped to the assembled eastern chipmunk reference genome using BWA mem v.0.7.17 (H. Li and R. Durbin 2009).”
InfluentialKhokhar, E. S., & Lozada, D. N. (2026) · G3 · doi:10.1093/g3journal/jkag116
“FASTQ files were aligned to the Zunla-1 ( C. annuum L.) reference genome (Qin et al. 2014) using the Burrows–Wheeler Aligner (Li and Durbin 2010).”
von Maydell, D., Schwerdt, J., Lehnert, H., Pöschl-Grau, Y., Schmutzer, T., & Marthe, F. (2026) · BMC Plant Biology · doi:10.1186/s12870-026-08853-8
“Trimmed reads were mapped against the ‘mock refer-ence’ using BWA-mem (Galaxy Version 0.7.18; [37, 38]).”
InfluentialLi, Z., Ren, M.-L., Hu, A., Meng, F.-F., & Wang, J.-J. (2026) · Molecular Ecology · doi:10.1111/mec.70367
“7.17) (Li and Durbin 2010), and SAMtools (v1.”
InfluentialSchramm, D., & Burg, T. (2026) · Ecology and Evolution · doi:10.1002/ece3.73650
“The reference genome was indexed using samtools 0.1.2 (Danecek et al. 2021) and the Burrows-Wheeler Alignment Tool (bwa) aligned the forward and reverse reads (Li and Durbin 2010).”
InfluentialEvolution of Resistance to Avian Malaria Infection in an Endemic Hawaiian Honeycreeper
Neddermeyer, J. H., Cassin‐Sackett, L., Paxton, E. H., Campana, M. G., Fleischer, R. C., & Foster, J. T. (2026) · Ecology and Evolution · doi:10.1002/ece3.73550
“Trimmed FastQ reads were aligned to the reference Oʻahu ʻamakihi genome using BWA-MEM 0.7.17 (Li and Durbin 2010).”
InfluentialGeviti, A., Pagano, L., Grassi, M., Saraceno, C., Facconi, A., Fostinelli, S., Laganà, V., Giacomucci, G., Cotelli, M., Cantoni, V., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27094081
“Adapters and low-quality reads were filtered out using Trimmomatic (version 0.39) [37], while the remaining high-quality reads were mapped to the GRCh38/hg38 reference genome employing BWA-MEM (version 0.7.17-r1188) [38].”
InfluentialXu, M., Zhang, R., Fan, S.-Q., Sun, M., & Zhang, X. (2026) · Genes · doi:10.3390/genes17050565
“Sequence reads were then mapped to the reference human genome (GRCh38/hg38) using Burrows-Wheeler Aligner (BWA) software (v.0.7.17) [9].”
InfluentialChen, L., Zhang, B., Zhang, D.-X., Gao, S.-Z., Li, C.-X., Huang, X.-L., & Cui, Y.-Q. (2026) · Journal of Archaeological Science: Reports · doi:10.1016/j.jasrep.2026.105718
Ndou, M., Potts, W. M., Duong, T. A., Teske, P. R., Childs, A.-R., & Henriques, R. (2026) · Evolutionary Applications · doi:10.1111/eva.70247
Niu, Y., Wang, R., Wang, L., Huang, A.-Z., Han, X., Yu, R., Chen, S.-J., Wang, J.-T., Cheng, J.-W., Chen, C.-M., et al. (2026) · Journal of genetics and genomics = Yi chuan xue bao · doi:10.1016/j.jgg.2026.04.017
Identifying unknown contributors to two-person DNA mixtures via whole-genome sequencing.
Lei, Y.-T., Liu, Z., Han, S., Lin, X., Sun, Q., & Ou, X. (2026) · Forensic Science International: Genetics · doi:10.1016/j.fsigen.2026.103530
Genomic insights into the admixture history and adaptive evolution of the Zhuang people
Mao, C., Li, S., Lu, Y., Liu, Q., Deng, L., Gao, Y., Zhang, X., Chen, H., Yang, Y., & Xu, S. (2026) · Molecular Biology and Evolution · doi:10.1093/molbev/msag105
“Reads were merged, adaptors were trimmed, and sequences were mapped to the human reference genome (GRCh38) using the Burrows-Wheeler Aligner (Li and Durbin 2010).”
Grossfurthner, L. P., Islam-Faridi, N., Hohenlohe, P. A., Waits, L. P., & Richardson, B. (2026) · American-Eurasian journal of botany · doi:10.1002/ajb2.70206
Zhang, H.-L., Cui, W., Liu, Y.-L., Zheng, W., Zeng, Y.-H., Sun, M.-L., Li, Y., Deng, L.-Y., Zeng, H., Zhao, B.-Y., et al. (2026) · Plant Diversity · doi:10.1016/j.pld.2026.05.009
Wen, S.-L., Zhou, K., Min, Y., Yang, K., Shang, C.-Q., Peng, L., Cai, X.-W., Leng, Y.-X., Shen, L.-N., Deng, L., et al. (2026) · Horticulture Research · doi:10.1093/hr/uhag174
“7.18 [ 51] was first utilized to map the genomic sequencing data of each individual to the R. delavayi genome.”
InfluentialRorippa islandica: a genetically accessible dicot model system to study flooding tolerance
Bartylla, M. M., Düthorn, E. L. R., Müller, J., Wirtz, M., van Veen, H., Sasidharan, R., & Mustroph, A. (2026) · Plant Physiology · doi:10.1093/plphys/kiag254
“Reads were mapped to the reference transcriptome of R. island-ica with the Burrows–Wheeler Aligner maximal exact matches algorithm ( Li and Durbin 2010).”
Genomics Insights into the Demographic History and Introgression of Tibetan Pigs
Xue, P.-X., Zha, C.-W., Luo, Y.-B., Huang, N., Liu, N., Wang, H., & Fang, M.-Y. (2026) · Animals · doi:10.3390/ani16091328
“7.19) [18].”
InfluentialYerramilli, N. P., Hasan, F., Sanjeev, S., Kapoor, P., Rahman, K., & Kashyap, R. (2026) · International Journal of Molecular and Immuno Oncology · doi:10.25259/ijmio_29_2025
Liu, M., Du, M., Xi, Z., Tastambek, K., Bao, Y., Song, X.-T., Zhou, A.-N., & Wang, Y.-Y. (2026) · Applied and Environmental Microbiology · doi:10.1128/aem.00268-26
“1.2; https://github.com/voutcn/megahit) (38).”
InfluentialSilver-Gorges, I., Komoroske, L., Adkins, J. L., Swenson, J. D., Addison, D. S., Burkholder, D. A., Bagley, D., Goodwin, G. D., Hart, K. M., Pfaller, J. B., et al. (2026) · Conservation Genetics · doi:10.1007/s10592-026-01783-w
“7.17; Li and Durbin 2010).”
InfluentialFigueroa-Ildefonso, E., Cabrera-Sosa, L., Kattenberg, J. H., Valdivia, H., Delgado-Ratto, C., Rosanas-Urgell, A., & Gamboa, D. (2026) · Scientific Reports · doi:10.1038/s41598-026-48246-3
“The trimmed reads were competitively mapped against the reference genome of the P. falciparum 3D7 (v3) and human (GRCh38.p13) reference genomes, using BWA-MEM version 0.7.17 27 .”
InfluentialTorres, H. F., Esparraga-Calle, A. V., Ascue, F., Fernandez-Castro, P., Heredia-Vilchez, L. A., Gongora-Bardales, D. J., Villegas, S. M. P., Trigoso-Yalta, M. J., Zamora-Huamán, S. J., Portocarrero, T., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-48764-0
Metabolome Diversity Enhances Resistance of Intertidal Clams to Thermal Stress
Zhi, H., Wei, X.-T., Lin, X., Ma, L., Zhang, T., & Dong, Y. (2026) · Integrative Zoology · doi:10.1111/1749-4877.70107
Whole-exome sequencing identifies PRSS56 variants in Chinese patients with microphthalmia
Luo, J., Li, K., Yang, R., Tang, M., & Ge, J. (2026) · BMC Medical Genomics · doi:10.1186/s12920-026-02376-9
“Raw reads in FASTQ format were quality-filtered to generate clean reads and then aligned to the human reference genome (UCSC hg38) using the Burrows-Wheeler Aligner (BWA) [19].”
Dickinson, Q., Yu, C., & Rivera-Mulia, J. (2026) · bioRxiv · doi:10.64898/2026.04.16.719037
“Alignment: Following preprocessing, sequencing reads are mapped to the reference genome using the Burrows-Wheeler Alignment (BWA-MEM) tool [36].”
Igh nuclear speckle association promotes V(D)J recombination
Priyadarshi, S., Bhat, K. H., Drake, E. B., Naiyer, S., Farooq, H., Qu, X.-Y., Cantillo, J., Lei, X., Ermiş, E., Kleiman, E., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-71577-8
“The pipeline was set up with BWA (0.7.15-r1140) 80 to map each read end separately to the mm10 reference genome (GRCm38).”
InfluentialGe, D., Zou, R., Jin, J., Shi, X., Wang, X., Zhang, D., Zhang, X., Zhang, Q., & Ning, C. (2026) · Archaeological and Anthropological Sciences · doi:10.1007/s12520-026-02466-w
“7.12 with the parameters -n and -l set to 0.01 and 1024, respectively (Li & Durbin, 2010).”
InfluentialRomanenko, M. N., Shikov, A., Shmatov, F., Savina, I. A., Belousov, M., Solovchenko, A., Chivkunova, O., Savelev, G. K., Kuznetsova, I., Karlov, D., et al. (2026) · Microbiology spectrum · doi:10.1128/spectrum.02919-25
Metadata
- Authors
- Li, H., & Durbin, R.
- Affiliations
- Wellcome Sanger Institute (GB)
- Corresponding author
- Durbin, Richard
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-15
- Volume
- 26
- Issue
- 5
- Pages
- 589-595
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- PMC
- PMC2828108
- OpenAlex
- W4247053599
- Cited by
- 12,063
- References
- 24
- Citations by year
- 2026: 639 · 2025: 972 · 2024: 1129 · 2023: 1067 · 2022: 1203 · 2021: 1245 · 2020: 1176 · 2019: 941 · 2018: 826 · 2017: 747 · 2016: 574 · 2015: 498 · 2014: 419 · 2013: 301 · 2012: 203
- FWCI
- 80.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Bioinformatics (publishedVersion, cc-by-nc)
- Funders
- Wellcome Trust (077192/Z/05/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Physical Sciences › Mathematics › Theoretical Computer Science › Algorithms and Data Compression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
- Keywords
- long-read alignment, Burrows-Wheeler transform, Smith-Waterman alignment, sequence alignment, reference genome, blat, alignment speed, alignment accuracy, human genome
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