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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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“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]
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“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
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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
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- Burrows, 1994, A block-sorting lossless data compression algorithm
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Liu, Y.-N., Gao, J.-J., Zhuang, X.-L., Wu, D.-D., & Sun, Y.-B. (2025) · Nature Communications · doi:10.1038/s41467-025-67031-w · Cited by 7
Yang, S., Zhang, H.-X., Xie, J., & Mao, X. (2025) · Molecular Ecology · doi:10.1111/mec.70184 · Cited by 7
“Read alignment was conducted using BWA-MEM Version 0.7.17 (Li and Durbin 2010) with default parameters.”
InfluentialSuzuki, H., Yoshida, K., Yokoi, A., Suzuki, K., Hirano, Y., Kitagawa, M., Asano‐Inami, E., Yoshihara, M., Nagao, Y., Tamauchi, S., et al. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-01122-1 · Cited by 5
Genomic insights into the population structure and genetic diversity of Ugandan indigenous cattle
Okwasiimire, R., Kugonza, D. R., Ruvinskiy, D., Weldenegodguad, M., Ghanem, N., Makgahlela, M., Ginja, C., Crooijmans, R., Kantanen, J., Uimari, P., et al. (2025) · Animal Genetics · doi:10.1111/age.70050 · Cited by 7
“7.17 (Li & Durbin, 2010) with default parameters (save for the -”
InfluentialA curated dataset of great ape genome diversity
Han, S., Riyahi, S., Huang, X., & Kuhlwilm, M. (2025) · Scientific Data · doi:10.1038/s41597-025-06124-z · Cited by 7
“15_GRCh38_no_alt_analysis_set from the UCSC genome browser) with bwa mem (version 0.7.16a) 52 , sorted with samtools (version 1.14) 53 and unmapped reads removed.”
InfluentialWang, M.-G., Duan, S., Sun, Q., Sun, Y.-T., Luo, L.-T., Liu, Y.-H., Tang, R., Yun, L., Liu, C., & He, G.-L. (2025) · medRxiv · doi:10.1101/2025.08.25.25334410 · Cited by 7
Seok, S., Vorsino, A. E., Collier, T. C., Hapairai, L. K., Jacobsen, C. M., Hasty, J. M., Romero-Weaver, A. L., Buckner, E. A., LaPointe, D., Leong, M., et al. (2025) · PLoS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0013414 · Cited by 7
“1) using B WA-MEM [43].”
InfluentialModulation of the cytoskeleton for cancer therapy
Matov, A. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1681065 · Cited by 7
“We used hg38 genome as reference and aligned the reads with BWA-MEM version 0.7.15 (Li and Durbin, 2010).”
InfluentialBian, J.-X., Zhang, Y.-L., Ding, S., Guo, H.-S., Li, K., Guan, Y., Zhou, G., Li, J.-H., Garg, V., Cui, Y.-Y., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02577-z · Cited by 6
“For assembly assessment, genome accuracy was evaluated by aligning Illumina reads and the long reads (HiFi and ONT) to the six peanut genomes using BWA-MEM (v.0.7.17-r1188) 65 and minimap2 (v.2.24-r1122) 66 .”
InfluentialOkwasiimire, R., Kugonza, D. R., Gao, J., Weldenegodguad, M., Makgahlela, M. L., Ghanem, N., Ginja, C., Crooijmans, R. P. M. A., Kantanen, J., Uimari, P., et al. (2026) · Mammalian Genome · doi:10.1007/s00335-026-10193-9 · Cited by 6
“7.17 (H. Li and Durbin 2010).”
InfluentialGenetic control of non-coding RNAs in the human brain and their implications for complex traits
Chen, L., Guo, Y., Hou, J., Yang, W., Qi, T., & Yang, J. (2025) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2025.11.012 · Cited by 5
Quantifying Early-Stage Lung Adenocarcinoma Progression with a Radiomic Trajectory
Qiu, Z., Li, J., Dou, S., Meng, Q., Wang, M.-M., Li, H., Zhang, C., Xie, H., Jiang, B., Lin, J., et al. (2025) · npj Digital Medicine · doi:10.1038/s41746-025-02031-0 · Cited by 5
Self-citationFifteen millennia of human mitogenome evolution in Sicily
Tommasi, A., Agostini, R. B., Villani, G., Migliore, N. R., Vizzari, M. T., Cardinali, I., Gerlando, R. D., Nicolini, V., Sorasio, G., Santos, P., et al. (2025) · Science Advances · doi:10.1126/sciadv.ady1674 · Cited by 6
Domestication shaped the chromatin landscape of grain amaranth
Graf, C., Winkler, T. S., Maughan, P. J., & Stetter, M. G. (2025) · Nature Communications · doi:10.1038/s41467-025-66445-w · Cited by 9
Li, L., Tian, Z., Wu, X., Tan, Z., Xu, H., Xiang, Y., Chen, J., Zhao, H., Chen, W., Guo, L., et al. (2025) · Advanced Science · doi:10.1002/advs.202512509 · Cited by 5
Tong, X.-Y., Hu, J., Wen, H., Chen, C.-L., Tao, L.-L., Wu, J., Tian, Y., Jiang, H., Chen, L.-B., Qiao, D., et al. (2025) · Plant Diversity · doi:10.1016/j.pld.2025.09.002 · Cited by 6
Gaikwad, A., Wyrwoll, M. J., Koser, S. A., Emich, J., Kuß, J., Aravina, M., Krallmann, C., Gromoll, J., Kliesch, S., Laurentino, S., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105899 · Cited by 6
Aquarius helicase facilitates HIV-1 integration into R-loop enriched genomic regions
Penzo, C., Özel, I., Martinovic, M., Kuzman, M., Glavaš, D., Stanić, M., Reichenbach, T., Müller, T. G., Rheinberger, M., Godarzi, N., et al. (2025) · Nature Microbiology · doi:10.1038/s41564-025-02089-2 · Cited by 4
“Cleaned reads were mapped to the hg19 (human) reference genome using BWA (v.0.7.17-r1188) 69 .”
InfluentialGenomic epidemiology of Histoplasma in Africa
Mapengo, R. E., Maphanga, T. G., Jofre, G. I., Rader, J. A., Turissini, D., Birkhead, M., Kwabia, S. A., Sepúlveda, V. E., Buitrago, M. J. S., Teixeira, M. D. M., et al. (2025) · mBio · doi:10.1128/mbio.00564-25 · Cited by 6
Zheng, Z.-K., Li, X.-Q., Huang, S., Wang, X., Jia, X., Wang, H., Zhou, J., & Ma, L. (2025) · Environment International · doi:10.1016/j.envint.2025.109752 · Cited by 6
Nash, D., Knapp, J. J., Overton, A. K., Hungwe, Y. C., Menon, R., Nissimov, J., & Charles, T. C. (2025) · bioRxiv · doi:10.1101/2025.07.29.667219 · Cited by 6
Albanus, R. D., Zhang, X., Zhao, Z., Taylor, H. J., Tang, X., Han, Y., Orchard, P., Varshney, A., Zhang, T., Manickam, N., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116065 · Cited by 25
Fast, cost-effective and flexible DNA sequencing by roll-to-roll fluidics
Qin, Y., Koehler, S., Ling, Y., Yu, S., Zhang, Y., Luo, J., Chen, K., Junjie, L., Zeng, J.-H., Chu, H., et al. (2025) · Nature Methods · doi:10.1038/s41592-025-02730-2 · Cited by 6
“Compared with the human genome (hs37d5) 32 , our sequencing results show a mapping rate of 99.9%.”
InfluentialHu, Z.-C., & Dong, Y.-W. (2025) · Marine Pollution Bulletin · doi:10.1016/j.marpolbul.2025.118439 · Cited by 6
Wang, W., Ren, J., Li, J., Li, D.-N., Wei, Z.-Y., Li, X., Fan, H.-M., Zhang, Y.-J., Xu, J.-Y., Xu, G., et al. (2026) · Science China Life Sciences · doi:10.1007/s11427-025-3206-7 · Cited by 5
“1) using BWA-MEM (v.0.7.17) (Li and Durbin, 2010).”
InfluentialTryptophanase disruption promotes insect–bacterium mutualism
Wang, Y., Moriyama, M., Koga, R., Oguchi, K., Hosokawa, T., Takai, H., Shigenobu, S., Nikoh, N., & Fukatsu, T. (2026) · Nature Microbiology · doi:10.1038/s41564-026-02264-z · Cited by 5
Convergent and lineage-specific genomic changes shape adaptations in sugar-consuming birds
Osipova, E., Ko, M., Petricek, K. M., Sin, S. Y. W., Brown, T. F., Winkler, S., Pippel, M., Jarrells, J., Weiche, S., Mosbech, M., et al. (2026) · Science · doi:10.1126/science.adt1522 · Cited by 18
RLBWT-Based LCP Computation in Compressed Space for Terabase-Scale Pangenome AnalysisPreprint
Sanaullah, A., Brown, N. K., Shakya, P., Deegutla, A., Naseri, A., Langmead, B., Zhi, D., & Zhang, S.-J. (2026) · bioRxiv · doi:10.64898/2026.01.23.701410 · Cited by 5
“…whole genome alignment [Delcher et al., 1999, Lin and Hsu, 2020], read mapping [Langmead et al., 2009, Li and Durbin, 2009], read alignment [Li and Durbin, 2010], identical by descent (IBD) segment detection [Freyman et al., 2020, Naseri et al., 2019], metagenomic or taxonomic…”
CAR-adapted PIK3CD base editing enhances T cell anti-tumor potency
Bucher, P., Brückner, N., Kortendieck, J., Grimm, M., Schleicher, J. T., Bartels, K., Hardy, S., Rausch, M., Wurzer, H., Thiemann, M., et al. (2026) · Nature Cancer · doi:10.1038/s43018-025-01099-7 · Cited by 2
“Reads were aligned to the reference sequences around the amplified loci using the BWA-MEM2 alignment algorithm 58 and variants were called using the LoFreq variant caller application 59 .”
Compiling an early life human gut microbiome atlas and identification of key microbial drivers
Tarracchini, C., Longhi, G., Gennaioli, E., Muscò, A., Rizzo, S. M., Viappiani, A., Vitale, S. G., Mancabelli, L., Lugli, G., Angioni, S., et al. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00868-7 · Cited by 5
“Next,thereadsweremappedto the Homo sapiens reference genome (GRCh38.p13 assembly) using BWA software to remove any human-derived metagenomic sequences.”
InfluentialImproved HIV-1 Subtyping Accuracy Using near Full-Length Sequencing: A Comparison of Common Tools
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“Reads were aligned to the HXB2 reference genome (GenBank accession number K03455) using Burrows-Wheeler Aligner version 0.7.13 (BWA-SW algorithm) [43], and variants were called using the Variant Caller plugin.”
InfluentialEight millennia of continuity of a previously unknown lineage in Argentina
Maravall-López, J., Motti, J. M. B., Pastor, N., Tavella, M. P., Fabra, M., Babot, M. D. P., Bonomo, M., Cornero, S., Lamenza, G. N., Leon, C., et al. (2025) · Nature · doi:10.1038/s41586-025-09731-3 · Cited by 8
Spruijtenburg, B., Meis, J. F. G. M., van Rhijn, N., Čurdová, M., Kašperová, E., Vašek, P., Bartoníčková, L., Kubele, J., Olišarová, P., Svobodová, K., et al. (2025) · Eurosurveillance · doi:10.2807/1560-7917.es.2025.30.45.2500285 · Cited by 6
“2) using BWA-MEM version 0.7.17 [14] and binary alignment map (BAM) files were filtered as described previously [15].”
InfluentialGenomic insights into karyotype evolution and adaptive mechanisms in Polygonaceae species
Liu, Z., Li, M., Wang, Y., Li, T., Li, W., Xing, L., Du, H., & He, Q. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116558 · Cited by 5
Optimizing ancient DNA recovery from archaeological plant seeds
Bolognesi, G., Latorre, A., Marini, M., Codato, A., Fontani, F., Saggioro, F., Luiselli, D., Basso, P., Cilli, E., & Bellin, D. (2025) · Scientific Reports · doi:10.1038/s41598-025-21743-7 · Cited by 4
“1) 66 genome (https://grapedia.org/files-download/) 67 using the BWA aln algorithm 68 , applying parameters optimized for ancient DNA (-l 1024, -n 0.01, -o 2) as recommended by Schubert et al. 69 .”
InfluentialJiang, T., Sun, Y.-H., Wang, Y., Luo, J., Liu, L., Chen, H., Xue, Y., Wang, L., Gao, K., Chen, D.-L., et al. (2025) · Molecular Horticulture · doi:10.1186/s43897-025-00175-x · Cited by 5
“7.17-r1188) (Li and Durbin 2010; Deng et al. 2024).”
InfluentialLopez-Gomez, J., Cerrato-Izaguirre, D., Quezada-Maldonado, E. M., Gaitán-Cepeda, L., Salcedo, M., Castillo, M. A. H., Granados-García, M., Sánchez-Pérez, Y., & García-Cuellar, C. (2025) · Cancers · doi:10.3390/cancers17203282 · Cited by 5
“7.8-r455) [32].”
InfluentialUno, Y., Fukunaga, K., Ushirozako, G., Murayama, N., Mizukami, K., Aoi, T., Tomiyasu, H., Honnami, M., Tsujimoto, H., Sakaguchi, M., et al. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117394 · Cited by 5
Han, S., Wang, J., Lin, T., Zhang, J.-P., Canário, A., Liu, Q.-G., & Chen, L.-B. (2025) · Molecular Ecology · doi:10.1111/mec.70104 · Cited by 5
“Filtered reads from all individuals were aligned to the C. nasus reference genome (Ma et al. 2023) using the Burrows-Wheeler Aligner v.0.7.15 (H. Li and Durbin 2010).”
Influential
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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